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Hosseini HC, Kammien AJ, Bach K, Allam O, Grauer JN, Colen DL. Distal Radius Fracture in the Setting of Human Immunodeficiency Virus: Management and Adverse Events. J Hand Surg Am 2025; 50:451-458. [PMID: 39895439 DOI: 10.1016/j.jhsa.2024.12.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 11/18/2024] [Accepted: 12/19/2024] [Indexed: 02/04/2025]
Abstract
PURPOSE Previous research has highlighted the elevated fracture risk among patients with human immunodeficiency virus (HIV). The current study assesses the association between HIV and the management and adverse events of distal radius fractures. METHODS Patients with a distal radius fracture from 2016 to 2022 were identified in a national administrative database. Patients were stratified by HIV status, and antiretroviral therapy (ART) use was identified. Fracture treatment modality (open or closed) was determined, and adverse events were identified within 1 year of fracture. Treatment modality and adverse events were compared using logistic regression and chi-square tests, respectively. RESULTS Among 396,544 patients with a distal radius fracture, 2,392 had HIV. HIV status was not associated with treatment modality. For patients with closed treatment, those with HIV had greater rates of malunion or nonunion and wrist arthritis. For patients with open treatment, HIV was also associated with greater incidence of malunion or nonunion. When stratifying by ART status, patients not on ART were less likely to undergo open treatment, whereas those with ART underwent open treatment at similar rates to HIV-negative patients. Compared with the HIV-negative cohort, those with HIV, and on ART were significantly more likely to sustain malunion or nonunion following closed treatment. CONCLUSIONS Patients with HIV are at increased risk for fracture, and they are more likely to experience adverse events following both closed and open management of distal radius fractures. Surgeons should pay close attention to bone healing in patients with HIV, and future research should investigate the causes of these adverse events and assess their modifiable risk factors. TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic II.
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Affiliation(s)
- Helia C Hosseini
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT
| | - Alexander J Kammien
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT
| | - Karen Bach
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT
| | - Omar Allam
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT
| | - Jonathan N Grauer
- Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT
| | - David L Colen
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT.
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Mannarino T, D'Antonio A, Mercinelli S, Falzarano M, Volpicelli F, Mainolfi CG, Zappulo E, Di Filippo G, Cotugno MR, Gentile I, Cuocolo A. Trabecular bone score assessed by dual-energy X ray absorption predicts vertebral fractures in HIV infected young adults. Bone Rep 2024; 22:101797. [PMID: 39247221 PMCID: PMC11379590 DOI: 10.1016/j.bonr.2024.101797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 07/18/2024] [Accepted: 08/12/2024] [Indexed: 09/10/2024] Open
Abstract
Introduction Bone mineral density (BMD) is reduced in patients with human immunodeficiency virus (HIV) infection. Trabecular bone score (TBS) is an additional feature calculated by dual-energy X ray absorption (DXA) that measures texture inhomogeneity at lumbar spine level, providing an index of bone microarchitecture. However, its clinical value still needs to be fully addressed. Aims of the study were to assess BMD and TBS in a cohort of patients with HIV compared to a population of healthy subjects and to investigate the prognostic value of TBS in HIV infected patients. Method Bone health was assessed by DXA in 165 patients with HIV infection (120 men, mean age 40 ± 7 years) and in 164 healthy subjects (53 male, mean age 37 ± 10 years). BMD was measured at level of lumbar spine (L1-L4), femoral neck and total hip. TBS was computed from the images of lumbar spine using machine proprietary software. Results BMD at femoral neck level was similar in HIV infected patients and healthy subjects (p = 0.57), whereas BMD measured in total femur was lower in HIV infected patients compared to healthy subjects (p < 0.05). Although mean BMD in lumbar spine was similar between HIV infected patients and healthy subjects (p = 0.90), mean lumbar TBS was lower in patients with HIV infection compared to healthy subjects (p < 0.05). Age, sex and HIV infection resulted independent predictors of reduced TBS. In HIV infected patients age, sex and protease inhibitor duration resulted independent predictors of reduced TBS. TBS was a significant predictor of vertebral fractures during follow-up (p < 0.05). Conclusion Patients with HIV infection have a significant reduction of TBS, a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement.
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Affiliation(s)
- Teresa Mannarino
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Adriana D'Antonio
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Simona Mercinelli
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Maria Falzarano
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Federica Volpicelli
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Ciro Gabriele Mainolfi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Giovanni Di Filippo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Maria Rosaria Cotugno
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Alberto Cuocolo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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Shao Y, Sun J, Kong K, Zhang R, Zhang R, Liu L, Wang J, Shen Y, Wu L, Zheng Z, Sun M, Qi T, Wang Z, Tang Y, Sun J, Song W, Yang J, Xu S, Zhao B, Shan F, Qin A, Lu H, Chen J. Prevalence and associated factors of low bone mineral density in people living with HIV: a cross-sectional study. Arch Osteoporos 2024; 19:56. [PMID: 38954143 DOI: 10.1007/s11657-024-01413-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 06/20/2024] [Indexed: 07/04/2024]
Abstract
This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. PURPOSE HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. METHODS We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. RESULTS A total of 829 individuals were included in this study, comprising the HIV group (n = 706) and the non-HIV group (n = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12-12.65; P < 0.001) and OR of 4.83 in the ART-experienced population (3.20-7.29, P < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24-10.14, P < 0.05), along with lower BMI (OR = 0.84, 0.75-0.95, P < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01-1.03, P < 0.01). CONCLUSION The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.
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Affiliation(s)
- Yueming Shao
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Jinfeng Sun
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Keyu Kong
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rengyin Zhang
- Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Renfang Zhang
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Li Liu
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Jiangrong Wang
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Yinzhong Shen
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Luling Wu
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhihang Zheng
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Meiyan Sun
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Tangkai Qi
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Zhenyan Wang
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Yang Tang
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Jianjun Sun
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Wei Song
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Junyang Yang
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Shuibao Xu
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Bihe Zhao
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
| | - Fei Shan
- Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - An Qin
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongzhou Lu
- Department of Infectious Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 518112, China.
| | - Jun Chen
- Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
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Fernández A, Imaz A. Clinical considerations when switching antiretroviral therapy. Expert Rev Clin Pharmacol 2024; 17:565-577. [PMID: 38850057 DOI: 10.1080/17512433.2024.2365826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/05/2024] [Indexed: 06/09/2024]
Abstract
INTRODUCTION Antiretroviral therapy (ART) can be personalized through simple formulations with high resistance barriers, favorable safety profiles, and novel administration routes. Switching treatments has become a key clinical strategy for addressing drug toxicity and interactions and enhancing adherence and convenience. This strategy aims to improve the quality of life and long-term efficacy, even in challenging cases like people living with HIV (PLWH) with multiple comorbidities, prior virological failure, and drug resistance. AREAS COVERED The authors reviewed clinical trials and cohort studies providing evidence of benefits and risks of current antiretroviral (ARV) drugs as switching options for PLWH in various scenarios. The literature search included clinical trials, meta-analyses, observational studies, and review articles in English published after 2000, and current HIV treatment guidelines in English and Spanish as of February 2024. EXPERT OPINION New ARV drugs offer advantages in efficacy and safety over previous options but may also have adverse effects. Second-generation integrase inhibitors and tenofovir alafenamide show benefits as switching options in various scenarios, though more research is needed on potential weight gain and metabolic issues. Injectable long-acting ART is promising for switching strategies, but finding the optimal combination of new drugs remains challenging.
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Affiliation(s)
- Analuz Fernández
- Human Immunodeficiency Virus (HIV) and Sexually Transmitted Infections (STI) Unit, Department of Infectious Diseases, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Arkaitz Imaz
- Human Immunodeficiency Virus (HIV) and Sexually Transmitted Infections (STI) Unit, Department of Infectious Diseases, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
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McGee DM, Cotter AG. HIV and fracture: Risk, assessment and intervention. HIV Med 2024; 25:511-528. [PMID: 38087902 DOI: 10.1111/hiv.13596] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 11/17/2023] [Indexed: 05/09/2024]
Abstract
OBJECTIVES With management of comorbidity in people living with HIV (PLWH) a key component of clinical care, early loss of bone integrity and clinical fracture are recognized as important issues. This review aims to describe the epidemiology of fracture in PLWH, as well as summarizing the relative balance of factors that contribute to fracture. We also aim to describe fracture risk assessment and interventional strategies to modify the risk of fracture in this population. RESULTS Data from recent meta-analyses show that PLWH have significantly more fractures than the general population, with men and injecting drug users at higher risk. Modifiable factors that contribute to fracture risk in this cohort include body mass index (BMI), drug use, concurrent medications, frailty, and hepatitis C virus infection. Relating to antiretroviral therapy, current or ever tenofovir exposure has been identified as predictive of fracture but not cumulative use, and a potentially modest protective effect of efavirenz has been observed. Fracture Risk Assessment Tool scores underestimate fracture risk in PLWH with improved accuracy when HIV is considered a cause of secondary osteoporosis and bone mineral density (BMD) included. CONCLUSION Early consideration of risk, prompting evaluation of modifiable risk factors, frailty and falls risk with bone density imaging and prompt intervention may avert fracture in PLWH. Guidance on screening and lifestyle modification is available in international guidelines. Bisphosphonates are safe and effective in PLWH, with limited data for other agents.
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Affiliation(s)
- D M McGee
- Department of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Republic of Ireland
| | - A G Cotter
- Department of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Republic of Ireland
- UCD Centre for Experimental Pathogen Host Research (CEPHR), University College Dublin, Dublin, Republic of Ireland
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Vélez-Díaz-Pallarés M, Delgado-Silveira E, Fernández-Fradejas J, Montero-Llorente B, Palomar-Fernández C, Montero-Errasquín B, Cruz-Jentoft AJ, Álvarez-Díaz A. Potentially Inappropriate Prescribing in Older People Living With HIV: A Scoping Review. J Acquir Immune Defic Syndr 2023; 94:445-460. [PMID: 37851956 DOI: 10.1097/qai.0000000000003298] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 08/21/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND Antiretroviral therapy has transformed HIV from a progressive and often fatal infection to a chronic disease. Currently, people living with HIV (PLHIV) have near-normal life expectancy; however, they face accelerated ageing and a rise in non-AIDS-defining HIV-associated conditions. Comorbidities increase the number of prescribed drugs and, therefore, the risk of polypharmacy and prescribing potentially inappropriate medications (PIMs). Still, there are no specific tools to identify PIMs in older PLHIV, which opens a pathway to investigate the particularities in the prescription of medication in this population. METHODS We conducted a scoping review in 5 electronic databases for studies reporting the use of tools to identify PIMs in older PLHIV. No language or date restrictions were applied. To complete the search, abstracts published in the most relevant HIV Conferences and Events in their editions from 2010 to 2022 were screened. RESULTS Of 50,193 records returned (13,701 of the databases and 36,492 of the Congresses), 39 studies met the inclusion criteria. Most studies were single-centre and conducted in Europe. Twenty-eight studies were cross-sectional, and most researchers used explicit criteria, mainly Beers and STOPP-START criteria, to identify PIMs. CONCLUSIONS Potentially inappropriate prescribing is frequent among older PLHIV. Explicit conventional tools to identify PIMs in older populations may need to be adapted to tackle the needs of PLHIV. Implicit tools may be more valid, although their use is more time-consuming, and standardization is complex.
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Affiliation(s)
| | - Eva Delgado-Silveira
- Servicio de Farmacia, Hospital Universitario Ramón y Cajal, IRYCIS. Madrid, Spain; and
| | | | | | | | | | | | - Ana Álvarez-Díaz
- Servicio de Farmacia, Hospital Universitario Ramón y Cajal, IRYCIS. Madrid, Spain; and
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Hechter RC, Zhou H, Leyden WA, Yuan Q, Pak KJ, Lam JO, Alexeeff S, Lea A, Hu H, Marcus JL, Rivera AS, Adams AL, Horberg MA, Towner WJ, Lo JC, Silverberg MJ. Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems. J Acquir Immune Defic Syndr 2023; 94:341-348. [PMID: 37884055 DOI: 10.1097/qai.0000000000003274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 07/10/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. SETTING Retrospective analyses of electronic health record data from 3 US integrated health care systems. METHODS Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. RESULTS Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). CONCLUSIONS Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.
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Affiliation(s)
- Rulin C Hechter
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
| | - Hui Zhou
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
| | - Wendy A Leyden
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Qing Yuan
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Katherine J Pak
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Jennifer O Lam
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Stacey Alexeeff
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Alexandra Lea
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Haihong Hu
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD
| | - Julia L Marcus
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA; and
| | - Adovich S Rivera
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Annette L Adams
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | - Michael A Horberg
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD
| | - William J Towner
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
| | - Joan C Lo
- Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Michael J Silverberg
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA; and
- Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA
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Schwenke JM, Thorball CW, Schoepf IC, Ryom L, Hasse B, Lamy O, Calmy A, Wandeler G, Marzolini C, Kahlert CR, Bernasconi E, Kouyos RD, Günthard HF, Ledergerber B, Fellay J, Burkhalter F, Tarr PE. Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study. J Infect Dis 2023; 228:742-750. [PMID: 37225667 PMCID: PMC10503954 DOI: 10.1093/infdis/jiad179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 05/14/2023] [Accepted: 06/23/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH. METHODS Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011-2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. RESULTS We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9). CONCLUSIONS In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.
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Affiliation(s)
- Johannes M Schwenke
- University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz
| | - Christian W Thorball
- Precision Medicine Unit, Lausanne University Hospital, University of Lausanne
- School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
| | - Isabella C Schoepf
- University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland
| | - Lene Ryom
- CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen
- Department of Infectious Diseases, Hvidovre University Hospital, Denmark
| | - Barbara Hasse
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
| | - Olivier Lamy
- Bone Unit, Lausanne University Hospital, University of Lausanne
| | | | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland
| | - Catia Marzolini
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel
| | | | - Enos Bernasconi
- Division of Infectious Diseases, Ospedale Regionale Lugano, University of Geneva and Università della Svizzera italiana, Lugano
| | - Roger D Kouyos
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
- Institute of Medical Virology, University of Zurich
| | - Huldrych F Günthard
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
- Institute of Medical Virology, University of Zurich
| | - Bruno Ledergerber
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
| | - Jacques Fellay
- Precision Medicine Unit, Lausanne University Hospital, University of Lausanne
- School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne
| | - Felix Burkhalter
- University Department of Nephrology and Dialysis, Kantonsspital Baselland, University of Basel,Bruderholz, Switzerland
| | - Philip E Tarr
- University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz
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Nabwire F, Hamill MM, Fowler MG, Byamugisha J, Kekitiinwa A, Prentice A. Biochemical Markers of Calcium and Bone Metabolism during and after Lactation in Ugandan Women with HIV on Universal Maternal Antiretroviral Therapy. J Bone Miner Res 2023; 38:1296-1311. [PMID: 37306529 PMCID: PMC10947145 DOI: 10.1002/jbmr.4866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 06/05/2023] [Accepted: 06/08/2023] [Indexed: 06/13/2023]
Abstract
We reported accentuated lactational decreases in areal bone mineral density and only partial skeletal recovery after lactation in Ugandan women with HIV (WWH) initiated on tenofovir disoproxil fumarate-based antiretroviral therapy (TDF-based ART) during pregnancy compared to women without HIV (REF). WWH also had higher breast milk calcium in the first months of lactation. To investigate the mechanisms, we measured bone turnover markers (bone resorption: C-terminal telopeptide [CTX]; bone formation: procollagen type 1 N-terminal propeptide [P1NP], bone-specific and total alkaline phosphatase [BALP, TALP]), hormones (parathyroid hormone [PTH], intact fibroblast growth factor 23 [FGF23], 1,25-dihydroxyvitamin D [1,25(OH)2 D]), vitamin D status (25-hydroxyvitamin D [25OHD]), and indices of mineral metabolism and renal function. Blood and urine samples collected at 36 weeks of gestation, 14 and 26 weeks of lactation, and 3-6 months after lactation were analyzed. Mean 25OHD was >50 nmol/L throughout. Both groups experienced similar biochemical changes during pregnancy and lactation to women in other settings, but within these patterns, the two groups differed significantly. Notably, WWH had higher PTH (+31%) and lower 1,25(OH)2 D (-9%) and TmP/GFR (-9%) throughout, lower P1NP (-27%) and plasma phosphate (-10%) in pregnancy, higher CTX (+15%) and BALP (+19%), and lower eGFR (-4%) during and after lactation. P1NP/CTX ratio was lower in WWH than REF in pregnancy (-21%), less so in lactation (-15%), and similar after lactation. Additionally, WWH had lower plasma calcium (-5%), lower FGF23 (-16%) and fasting urinary calcium (-34%) at one or both lactation timepoints, and higher fasting urinary phosphate (+22%) at 26 weeks of lactation and after lactation. These differences resemble reported TDF effects, especially raised PTH, increased bone resorption, decreased bone formation, and decreased renal function, and may explain the observed differences in bone mineral density and breast milk calcium. Further studies are needed to determine whether HIV and TDF-based ART have long-term consequences for maternal bone health and offspring growth. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Florence Nabwire
- MRC Epidemiology UnitUniversity of CambridgeCambridgeUK
- MRC Nutrition and Bone Health Research GroupCambridgeUK
- Formely based at the MRC Elsie Widdowson LaboratoryCambridgeUK
| | - Matthew M. Hamill
- MRC Nutrition and Bone Health Research GroupCambridgeUK
- Formely based at the MRC Elsie Widdowson LaboratoryCambridgeUK
- Johns Hopkins University School of MedicineBaltimoreMDUSA
| | | | | | - Adeodata Kekitiinwa
- Baylor College of Medicine Children's Foundation – Uganda (Baylor‐Uganda)KampalaUganda
| | - Ann Prentice
- MRC Epidemiology UnitUniversity of CambridgeCambridgeUK
- MRC Nutrition and Bone Health Research GroupCambridgeUK
- Formely based at the MRC Elsie Widdowson LaboratoryCambridgeUK
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10
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Cabrera DM, Cornejo MP, Slotkin R, Pinedo Y, Yu W, Guan W, Garcia PJ, Hsieh E. Prevalence of and risk factors for vertebral fracture and low bone mineral density among Peruvian women aging with HIV. Arch Osteoporos 2023; 18:64. [PMID: 37160770 PMCID: PMC10170032 DOI: 10.1007/s11657-023-01250-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 04/18/2023] [Indexed: 05/11/2023]
Abstract
Osteoporosis and fracture risk among women with HIV in Latin America is understudied. In a sample of Peruvian women with and without HIV, women with HIV had lower femoral neck and total hip BMD and a higher proportion of vertebral fractures. Important treatment gaps were identified across both groups. PURPOSE Studies have shown that patients with HIV are at increased risk for bone loss and fracture due to a combination of host, viral, and antiretroviral therapy (ART)-related factors. We aimed to explore the prevalence of vertebral fracture (VF) and low bone mineral density (BMD) among women aging with HIV in Peru and identify risk factors for osteoporosis and fracture in this population. METHODS We enrolled women living with and without HIV aged ≥40 years between 2019 and 2020. Participants completed a survey and obtained dual X-ray absorptiometry (DXA) test to assess BMD at the lumbar spine (LS), femoral neck (FN), and total hip (TH). A subset of patients also obtained lateral thoracolumbar X-rays. Presence of VF was determined using the Genant semiquantitative method. Regression analyses were used to model associations between key risk factors and BMD. RESULTS 104 women living with HIV and 212 women living without HIV were enrolled with a mean age of 52.4±8.2 and 56.4±8.8 years (p < 0.001). Among postmenopausal women (257/316, 81.3%), 26.3% of women living with HIV and 25.9% of those without HIV had osteoporosis. Among the 88 women living with HIV and 178 women living without HIV who obtained thoracolumbar X-rays, 12.5% and 6.2%, respectively, had at least one VF. Based on DXA and the FRAX score, 22/104 women living with HIV met criteria for osteoporosis treatment according to national guidelines; however, none were on treatment. Propensity score matching revealed that women living with HIV had 0.032 g/cm2 lower FN BMD (p = 0.012) and 0.034 g/cm2 lower TH BMD (p = 0.041) compared to women without HIV. CONCLUSION In this study, women living with HIV on long-standing ART had increased VF prevalence compared to the slightly older group of women without HIV. Age and BMI were independent predictors for BMD at the lumbar spine, hip, and femoral neck among women living with HIV, and there was a treatment gap among women who met criteria for osteoporosis treatment. Larger studies are needed in this region to identify individuals at risk for fracture and to inform prevention guidelines.
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Affiliation(s)
- Diego M Cabrera
- Section of Rheumatology, Allergy and Immunology, Yale School of Medicine, New Haven, CT, USA
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
- Epidemiology, STD, and HIV Unit, School of Public Health, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Mijahil P Cornejo
- Department of Rheumatology, Hospital Nacional Arzobispo Loayza, Lima, Peru
| | - Rebecca Slotkin
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Yvett Pinedo
- Department of Infectious Diseases, Hospital Nacional Arzobispo Loayza, Lima, Peru
| | - Wei Yu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenmin Guan
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Patricia J Garcia
- Epidemiology, STD, and HIV Unit, School of Public Health, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Evelyn Hsieh
- Section of Rheumatology, Allergy and Immunology, Yale School of Medicine, New Haven, CT, USA.
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11
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Zhang J, Tong Y, Liu Y, Lin M, Xiao Y, Liu C. Mechanical loading attenuated negative effects of nucleotide analogue reverse-transcriptase inhibitor TDF on bone repair via Wnt/β-catenin pathway. Bone 2022; 161:116449. [PMID: 35605959 DOI: 10.1016/j.bone.2022.116449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 12/19/2022]
Abstract
The nucleotide analog reverse-transcriptase inhibitor, tenofovir disoproxil fumarate (TDF), is widely used to treat hepatitis B virus (HBV) and human immunodeficiency virus infection (HIV). However, long-term TDF usage is associated with an increased incidence of bone loss, osteoporosis, fractures, and other adverse reactions. We investigated the effect of chronic TDF use on bone homeostasis and defect repair in mice. In vitro, TDF inhibited osteogenic differentiation and mineralization in MC3T3-E1 cells. In vivo, 8-week-old C57BL/6 female mice were treated with TDF for 38 days to simulate chronic medication. Four-point bending test and μCT showed reduced bone biomechanical properties and microarchitecture in long bones. To investigate the effects of TDF on bone defect repair, we utilized a bilateral tibial monocortical defect model. μCT showed that TDF reduced new bone mineral tissue and bone mineral density (BMD) in the defect. To verify whether mechanical stimulation may be a useful treatment to counteract the negative bone effects of TDF, controlled dynamic mechanical loading was applied to the whole tibia during the matrix deposition phase on post-surgery days (PSDs) 5 to 8. Second harmonic generation (SHG) of collagen fibers and μCT showed that the reduction of new bone volume and bone mineral density caused by TDF was reversed by mechanical loading in the defect. Immunofluorescent deep tissue imaging showed that chronic TDF treatment reduced the number of osteogenic cells and the volume of new vessels. In addition, chronic TDF treatment inhibited the expressions of periostin and β-catenin, but increased the expression of sclerostin. Both negative effects were reversed by mechanical loading. Our study provides strong evidence that chronic use of TDF exerts direct and inhibitory impacts on bone repair, but appropriate mechanical loading could reverse these adverse effects.
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Affiliation(s)
- Jianing Zhang
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
| | - Yanrong Tong
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
| | - Yang Liu
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
| | - Minmin Lin
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
| | - Yao Xiao
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
| | - Chao Liu
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
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12
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Alvarez E, Campbell L, Tinago W, Garcia-Leon A, Walsh I, Brady JJ, Burling K, Noe S, Neuville MF, Jouret F, Jamshidian F, Graham H, Rhee M, Mallon PW, Post FA. The renal-bone axis in older people living with HIV on stable antiretroviral therapy: A sub-analysis of the GS-US-104-0423 study. Antivir Ther 2022; 27:13596535221094898. [PMID: 36000318 DOI: 10.1177/13596535221094898] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Data on low bone mineral density (BMD) in people living with HIV (PLWH) are mainly derived from younger adults; little is known about how antiretroviral therapy (ART) and alterations in the renal-bone axis relate to BMD in older PLWH. METHODS Cross-sectional study of men > 50 years and post-menopausal women with HIV. Antiretroviral therapy exposure was stratified into four groups based on use of tenofovir disoproxil fumarate (TDF) and protease inhibitors (PI): non-TDF/non-PI, non-TDF/PI, TDF/non-PI, and TDF/PI. Bone mineral density was measured by dual X-ray absorptiometry (DXA). Bone turnover/regulatory markers and renal tubular function were analysed in stored plasma and urine samples. The association of ART exposure and bone/renal biomarkers on BMD was explored using logistic regression models. RESULTS 247 individuals (median [IQR] age 57 [53, 65] years; 47% female; 13% of Black ethnicity; CD4 count 643 [473, 811] cells/mm3; and 98% with HIV RNA < 200 copies/mL) were included. Bone turnover and renal tubular function differed significantly by ART exposure. In analyses adjusted for demographic and traditional renal/bone risk factors, exposure to TDF and PI was associated with a fourfold greater risk of low BMD at the femoral neck and exposure to TDF and/or PI with a threefold greater risk of low BMD at the lumbar spine. The relationship between ART and low BMD was not altered by further adjustment for bone turnover or renal tubular function markers. CONCLUSIONS The associations between low BMD and ART exposure (TDF vs. non-TDF and boosted vs. unboosted third agents) were minimally affected by adjustments for bone and kidney biomarkers.
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Affiliation(s)
- Elena Alvarez
- Centre for Experimental Pathogen Host Research, 8797University College Dublin School of Medicine, Dublin, Ireland
| | | | - Willard Tinago
- Centre for Experimental Pathogen Host Research, 8797University College Dublin School of Medicine, Dublin, Ireland
| | - Alejandro Garcia-Leon
- Centre for Experimental Pathogen Host Research, 8797University College Dublin School of Medicine, Dublin, Ireland
| | - Ian Walsh
- 8881Mater Misericordiae University Hospital, Dublin, Ireland
| | | | | | - Sebastian Noe
- MVZ Karlsplatz HIV Research and Clinical Care Center, Munich, Germany
| | - Marie F Neuville
- Laboratory of Translational Research in Nephrology, ULiege GIGA Research Center, Liege, Belgium
| | - Francois Jouret
- Laboratory of Translational Research in Nephrology, ULiege GIGA Research Center, Liege, Belgium
| | | | - Hiba Graham
- 2158Gilead Sciences, Inc., Foster City, CA, USA
| | - Martin Rhee
- 2158Gilead Sciences, Inc., Foster City, CA, USA
| | - Paddy W Mallon
- Centre for Experimental Pathogen Host Research, 8797University College Dublin School of Medicine, Dublin, Ireland
| | - Frank A Post
- 4616Kings College London, London, UK.,8948King's College Hospital NHS Foundation Trust, London, UK
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13
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Lieber M, Hamill MM, Pham P, Pine E, Crank J, Shah M. Navigating Human Immunodeficiency Virus and Primary Care Concerns Specific to the Transgender and Gender-Nonbinary Population. Open Forum Infect Dis 2022; 9:ofac091. [PMID: 35355890 PMCID: PMC8962744 DOI: 10.1093/ofid/ofac091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/22/2022] [Indexed: 11/14/2022] Open
Abstract
Human immunodeficiency virus (HIV) prevention and treatment remain critically important to outpatient care among transgender and gender-nonbinary individuals. Epidemiologically, trans men and trans women are significantly more likely to have HIV compared with all adults of reproductive age. Here, we provide an overview of unique primary care considerations affecting transgender and gender-nonbinary individuals, including screening and treatment of HIV and other sexually transmitted infections as well as cancer screening and fertility preservation options. We also seek to review current literature and clinical practice guidelines related to drug–drug interactions between antiretroviral therapy (ART) and gender-affirming hormonal therapy (GAHT). In short, integrase strand transfer inhibitor–based therapy is not expected to have significant drug interactions with most GAHT and is preferred in most transgender individuals, including those on GAHT. Clinicians should also remain aware of current GAHT regimens and consider tailoring ART and GAHT to reduce cardiovascular and other risk factors.
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Affiliation(s)
- Mark Lieber
- Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA
| | - Matthew M Hamill
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Paul Pham
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elyse Pine
- Chase Brexton Health Services, Baltimore, Maryland, USA
| | - Jill Crank
- Johns Hopkins Community Physicians, Baltimore, Maryland, USA
| | - Maunank Shah
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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14
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Li C, Li H, Gong M, Wei J. Osteopenia in a young man associated with the use of tenofovir disoproxil fumarate. Clin Case Rep 2022; 10:e05641. [PMID: 35356169 PMCID: PMC8956931 DOI: 10.1002/ccr3.5641] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/02/2022] [Accepted: 03/09/2022] [Indexed: 12/13/2022] Open
Abstract
Tenofovir disoproxil fumarate is a recommended first-line therapy for patients with chronic hepatitis B, although the frequent Tenofovir disoproxil fumarate related adverse drug reactions are nephrotoxicity and bone toxicity. We described the case of a 21-year-old Han Chinese male patient with chronic hepatitis B with tenofovir disoproxil fumarate-associated osteopenia. The patient presented osteopenia at the site of his femoral neck with bone mineral density 0.865g/cm2 (Z = -1.9) in January 2020. Nine months after switching to TAF, bone mineral density at left femoral neck improved to 0.978g/cm2 (Z = -1.0) in September 2020. Bone mineral density of this patients was normal in January 2021. This is the first report in very young man presenting tenofovir disoproxil fumarate-associated osteopenia.
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Affiliation(s)
- Chunmei Li
- Department of Infectious disease and hepatologyHospital of Yunnan UniversityYunnanChina
| | - Hui Li
- Department of Infectious disease and hepatologyHospital of Yunnan UniversityYunnanChina
| | - Ming Gong
- Department of Infectious disease and hepatologyHospital of Yunnan UniversityYunnanChina
| | - Jia Wei
- Department of Infectious disease and hepatologyHospital of Yunnan UniversityYunnanChina
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15
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Ho J, Kim B, Kim KS, Jihn CH, Kim MY, Kang DR, Park YH, Ahn J. Statin Supply and Polydrug Use in Older Adults: A Focus on Drug Combinations that Reduce Bone Density. Ann Geriatr Med Res 2022; 25:269-277. [PMID: 34986544 PMCID: PMC8749039 DOI: 10.4235/agmr.21.0103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/08/2021] [Indexed: 12/15/2022] Open
Abstract
Background We investigated the comorbidities of individuals who were prescribed statins to identify the use of bone mineral density (BMD)-reducing drugs, examine polydrug use trends involving these drugs, and explore their relationship with osteoporosis. Methods We analyzed claims data from the Korean National Health Insurance Service (January 2014–December 2018). We sampled 20% of 8,379,419 patients aged ≥50 years who were prescribed statins. Among them, we analyzed the data of those who were administered two or more prescriptions for 14 days or longer within 6 months of the initial date of statin prescription. Data on comorbidities and drugs that can potentially reduce BMD were obtained. Osteoporosis-related diagnoses were obtained as an outcome measure. The relationship between statins and BMD-reducing drugs was analyzed using logistic regression. Results Among the 4,138 statin users aged 50 years or older, 552 were diagnosed with osteoporosis. The most common comorbidity in statin users was hypertension, followed by ischemic heart disease, diabetes mellitus, and stroke. The most frequently administered BMD-reducing drugs were proton pump inhibitors (PPIs). The osteoporosis diagnosis rate was higher in patients who were prescribed both statins and PPIs or both statins and levothyroxine than in those using only a statin. Conclusion PPIs and levothyroxine should be prescribed cautiously in statin users and bone densitometry should be proactively performed considering the increased risk of osteoporosis.
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Affiliation(s)
- JaHyun Ho
- Division of Hospital Medicine, Korea Cancer Center Hospital, Seoul, Korea
| | - Bokyoung Kim
- Department of Nursing, Catholic Kwandong University, Gangneung, Korea
| | - Kue Sook Kim
- Health Care Center, Seoul Metropolitan Dongbu Hospital, Seoul, Korea
| | - Chang-Ho Jihn
- Department of Industrial and Management Systems Engineering, Kyung Hee University, Yongin, Korea
| | - Min-Young Kim
- Department of Dental Hygiene, Howon University, Gunsan, Korea
| | - Dae Ryong Kang
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - You Hyun Park
- Department of Biostatistics, Yonsei University, Seoul, Korea
| | - Jihyun Ahn
- Department of Internal Medicine, Korea Medical Institute, Seoul, Korea
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16
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Zeng J, Ye P, Wei D, Li L, Ma W. Tenofovir-induced osteopenia and hyperparathyroidism: A case report and literature review. Front Endocrinol (Lausanne) 2022; 13:1043954. [PMID: 36714555 PMCID: PMC9875041 DOI: 10.3389/fendo.2022.1043954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 12/19/2022] [Indexed: 01/13/2023] Open
Abstract
Tenofovir disoproxil fumarate is the first-line antiviral therapy for chronic viral hepatitis B, but long-term use is associated with renal failure and hypophosphatemic osteomalacia. Tenofovir disoproxil fumarate-induced osteoporosis and secondary hyperparathyroidism are less commonly reported. Herein, we describe the case of a patient with bone and multijoint pain who was initially misdiagnosed as having normocalcemic primary hyperparathyroidism associated with prolonged exposure to tenofovir disoproxil fumarate. The patient's 24-h urinary calcium and phosphorus excretion levels and serum calcium levels were at the lower end of the normal range. After reviewing these findings, the diagnosis was amended to osteoporosis and secondary hyperparathyroidism caused by tenofovir disoproxil fumarate. In this report, we describe the differences in clinical and laboratory manifestations of hyperparathyroidism induced by tenofovir disoproxil fumarate and normocalcemic primary hyperparathyroidism. We also discuss relevant pathophysiological mechanisms and propose a feasible treatment strategy.
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17
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OUP accepted manuscript. J Antimicrob Chemother 2022; 77:1974-1979. [DOI: 10.1093/jac/dkac137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 02/18/2022] [Indexed: 11/13/2022] Open
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18
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Brown TT, Yuhas K, Mayer KH, Landovitz RJ, Marzinke MA, Hendrix CW, Chen YQ, Klingman KL, Chege W, Mccauley MB, Gulick RM, Wilkin TJ. Bone changes with candidate PrEP regimens containing tenofovir disoproxil fumarate and/or maraviroc and/or emtricitabine in US men and women: HPTN 069/ACTG A5305. J Antimicrob Chemother 2021; 77:500-506. [PMID: 34791296 DOI: 10.1093/jac/dkab400] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 09/28/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Tenofovir disoproxil fumarate-containing pre-exposure prophylaxis (PrEP) has been associated with decreases in bone mineral density (BMD), but the bone effects of other non-tenofovir disoproxil fumarate candidate PrEP regimens are not well described. METHODS The HPTN 069/ACTG A5305 study randomized 406 US cisgender men and transgender women, and 188 cisgender women at risk for HIV infection to one of four double-blinded regimens: (i) maraviroc; (ii) maraviroc + emtricitabine; (iii) maraviroc + tenofovir disoproxil fumarate; or (iv) tenofovir disoproxil fumarate + emtricitabine. BMD was measured in a subset of participants at the lumbar spine (LS) and hip by dual-energy X-ray absorptiometry (DXA) at baseline and 48 weeks. Percentage change in LS and hip BMD was compared between the tenofovir disoproxil fumarate- and non-tenofovir disoproxil fumarate-containing arms by Wilcoxon rank-sum tests and multiple linear regression adjusting for sex, race and baseline BMI. RESULTS At baseline (n = 307), the median age was 33 years, 56% male and 43% black. At the hip, the median percentage change in BMD at 48 weeks was -1.05% in the tenofovir disoproxil fumarate arms and 0.0% in the non-tenofovir disoproxil fumarate arms (between group P = 0.001). No interaction by sex was observed. The median percentage change in LS BMD was not different between arms. CONCLUSIONS Tenofovir disoproxil fumarate-containing PrEP was associated with significantly greater bone loss compared with maraviroc ± emtricitabine PrEP at the hip, but not the LS. The BMD changes at the hip were similar in magnitude in men and women.
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Affiliation(s)
- Todd T Brown
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Krista Yuhas
- Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
| | - Kenneth H Mayer
- Fenway Health, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215, USA
| | - Raphael J Landovitz
- Department of Medicine, University of California, Los Angeles, Los Angeles,, CA 90025, USA
| | - Mark A Marzinke
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Craig W Hendrix
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Ying Q Chen
- Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
| | - Karen L Klingman
- HIV Research Branch, Therapeutics Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Wairimu Chege
- Clinical Prevention Research Branch, Prevention Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | | | - Roy M Gulick
- Department of Medicine, Weill, Cornell, Medicine, New York, NY 10065, USA
| | - Timothy J Wilkin
- Department of Medicine, Weill, Cornell, Medicine, New York, NY 10065, USA
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19
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Kim JH, Noh J, Kim W, Seong H, Kim JH, Lee WJ, Baek Y, Hyun J, Sohn Y, Cho Y, Kim MH, Ahn S, Lee Y, Ahn JY, Jeong SJ, Ku NS, Yeom JS, Kim C, Choi JY. Trends of age-related non-communicable diseases in people living with HIV and comparison with uninfected controls: A nationwide population-based study in South Korea. HIV Med 2021; 22:824-833. [PMID: 34263511 DOI: 10.1111/hiv.13139] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/04/2021] [Indexed: 01/25/2023]
Abstract
OBJECTIVES We aim to compare the trends of non-communicable diseases (NCDs) and death among people living with HIV (PLWH) and uninfected controls in South Korea. METHODS We identified PLWH from a nationwide database of all Korean citizens enrolled from 1 January 2004 to 31 December 2016. A control cohort was randomly selected for PLWH by frequency matching for age and sex in a 20:1 ratio. To compare NCD trends between the groups, adjusted incidence rate ratios for outcomes across ages, calendar years and times after HIV diagnosis were calculated. RESULTS We included 14 134 PLWH and 282 039 controls in this study; 58.5% of PLWH and 36.4% of the controls were diagnosed with at least one NCD. The incidence rates of cancers, chronic kidney disease, depression, osteoporosis, diabetes and dyslipidaemia were higher in PLWH than in the controls, whereas those of cardiovascular disease, heart failure, ischaemic stroke and hypertension were lower in PLWH. Relative risks (RRs) for NCDs in PLWH were higher than controls in younger age groups. Trends in the RRs of NCDs tended to increase with the calendar year for PLWH vs. controls and either stabilized or decreased with time after HIV diagnosis. The RR of death from PLWH has decreased with the calendar year, but showed a tendency to rise again after 2014 and was significant at the early stage of HIV diagnosis. CONCLUSIONS Although the RR of each NCD in PLWH showed variable trends compared with that in controls, NCDs in PLWH have been increasingly prevalent.
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Affiliation(s)
- Jung Ho Kim
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Juhwan Noh
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Woojin Kim
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Seong
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Jun Hyoung Kim
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Woon Ji Lee
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - YaeJee Baek
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - JongHoon Hyun
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Yujin Sohn
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Yunsuk Cho
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Moo Hyun Kim
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - SangMin Ahn
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Yongseop Lee
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Jin Young Ahn
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Su Jin Jeong
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Nam Su Ku
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Joon-Sup Yeom
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Changsoo Kim
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jun Yong Choi
- Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea
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Makras P, Petrikkos P, Anastasilakis AD, Kolynou A, Katsarou A, Tsachouridou O, Metallidis S, Yavropoulou MP. Denosumab versus zoledronate for the treatment of low bone mineral density in male HIV-infected patients. Bone Rep 2021; 15:101128. [PMID: 34541262 PMCID: PMC8441091 DOI: 10.1016/j.bonr.2021.101128] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 09/05/2021] [Accepted: 09/06/2021] [Indexed: 12/20/2022] Open
Abstract
Introduction We aimed to compare annual changes in the bone mineral density (BMD) at the lumbar spine (LS) and the femoral neck (FN) in males with HIV-associated osteoporosis treated with either zoledronate (ZOL) or denosumab (Dmab). Methods In this open label, 12-month, prospective, multicenter, cohort study, 23 male people living with HIV (PLWH) under antiretroviral therapy (ART) with low BMD were administered either a single iv infusion of ZOL 5 mg (n = 10) or Dmab 60 mg sc injections biannually (n = 13). Fourteen age-matched male PLWH with normal BMD served as controls. BMD was measured at baseline and at 12 months. Results LS-BMD increased within both treatment groups at 12 months (ZOL 5.43% ± 3.60%, p = 0.001; Dmab 5.76% ± 3.44%, p < 0.005) and decreased in controls (−2.58% ± 4.12, p = 0.04). FN-BMD increased in both treatment groups at 12 months (ZOL 7.23% ± 5.46%, p = 0.003; Dmab 3.01% ± 2.46%, p < 0.005), and remained unchanged in controls (1.22% ± 2.09, p = 0.06). LS-BMD changes did not differ between the two treatment groups, but FN-BMD changes were more prominent in the ZOL group (p < 0.05). None of our study cohort sustained new fragility fractures during the 12-month study period, and no case of acute phase response was recorded in the ZOL group. Conclusions In male PLWH under ART requiring osteoporosis treatment both ZOL and Dmab are efficient and well tolerated therapeutic options achieving BMD increases at least for the first year of treatment.
Zoledronate and denosumab are efficient therapies for HIV-associated osteoporosis. Zoledronate-induced acute phase response may be less frequent with concomitant ART. Alternative osteoporosis agent should follow in case of denosumab discontinuation. Significant annual BMD loss may occur in male PLWH under long term treatment with ART.
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Affiliation(s)
- Polyzois Makras
- Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece
| | - Panagiotis Petrikkos
- 2nd Department of Internal Medicine, 251 Hellenic Air Force & VA General Hospital, Athens, Greece
| | | | - Artemis Kolynou
- Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Angeliki Katsarou
- 2nd Department of Internal Medicine, 251 Hellenic Air Force & VA General Hospital, Athens, Greece
| | - Olga Tsachouridou
- Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Symeon Metallidis
- Infectious Diseases Unit, 1 Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Medical School, Thessaloniki, Greece
| | - Maria P Yavropoulou
- Endocrinology Unit, 1 Department of Propedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, LAIKO General Hospital of Athens, Greece
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21
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Battalora L, Armon C, Palella F, Li J, Overton ET, Hammer J, Fuhrer J, Novak RM, Carlson K, Spear JR, Buchacz K. Incident bone fracture and mortality in a large HIV cohort outpatient study, 2000-2017, USA. Arch Osteoporos 2021; 16:117. [PMID: 34337687 DOI: 10.1007/s11657-021-00949-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 05/03/2021] [Indexed: 02/03/2023]
Abstract
UNLABELLED We evaluated the association of bone fracture with mortality among persons with HIV, controlling for sociodemographic, behavioral, and clinical factors. Incident fracture was associated with 48% greater risk of all-cause mortality, underscoring the need for bone mineral density screening and fracture prevention. PURPOSE/INTRODUCTION Low bone mineral density (BMD) and fracture are more common among persons with HIV (PWH) than those without HIV infection. We evaluated the association of bone fracture with mortality among PWH, controlling for sociodemographic, behavioral, and clinical factors. METHODS We analyzed data from HIV Outpatient Study (HOPS) participants seen at nine US HIV clinics during January 1, 2000, through September 30, 2017. Incident fracture rates and post-fracture mortality were compared across four calendar periods. Cox proportional hazards analyses determined factors associated with all-cause mortality among all participants and those with incident fracture. RESULTS Among 6763 HOPS participants, 504 (7.5%) had incident fracture (median age = 47 years) and 719 (10.6%) died. Of fractures, 135 (26.8%) were major osteoporotic (hip/pelvis, wrist, spine, arm/shoulder). During observation, 27 participants with major osteoporotic fractures died (crude mortality 2.97/100 person-years [PY]), and 48 with other site fractures died (crude mortality 2.51/100 PY). Post-fracture, age- and sex-adjusted all-cause mortality rates per 100 PY decreased from 8.5 during 2000-2004 to 1.9 during 2013-2017 (P<0.001 for trend). In multivariable analysis, incident fracture was significantly associated with all-cause mortality (Hazard Ratio 1.48, 95% confidence interval 1.15-1.91). Among 504 participants followed post-fracture, pulmonary, kidney, and cardiovascular disease, hepatitis C virus co-infection, and non-AIDS cancer, remained independently associated with all-cause mortality. CONCLUSIONS Incident fracture was associated with 48% greater risk of all-cause mortality among US PWH in care, underscoring the need for BMD screening and fracture prevention. Although fracture rates among PWH increased during follow-up, post-fracture death rates decreased, likely reflecting advances in HIV care.
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Affiliation(s)
- Linda Battalora
- Colorado School of Mines, 1301 19th St., Golden, CO, 80401, USA. .,Cerner Corporation, Kansas City, MO, USA.
| | - Carl Armon
- Cerner Corporation, Kansas City, MO, USA
| | - Frank Palella
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jun Li
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Edgar T Overton
- University of Alabama School of Medicine, Birmingham, AL, USA
| | | | - Jack Fuhrer
- Stony Brook School of Medicine, Stony Brook, NY, USA
| | - Richard M Novak
- University of Illinois College of Medicine, Chicago, IL, USA
| | | | - John R Spear
- Colorado School of Mines, 1301 19th St., Golden, CO, 80401, USA
| | - Kate Buchacz
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
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22
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Ellis RJ, Paolillo E, Saloner R, Heaton RK. Higher comorbidity burden predicts worsening neurocognitive trajectories in people with HIV. Clin Infect Dis 2021; 74:1323-1328. [PMID: 34329400 DOI: 10.1093/cid/ciab655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Age-related comorbidities accumulate faster in people with HIV (PWH) than in those without (PWoH). We evaluated whether a validated multimorbidity scale, the Charlson Index, predicted neurocognitive trajectories in PWH. METHODS Scaled scores a comprehensive neuropsychological battery were averaged across all visits. Multilevel modeling examined between- and within-person predictors of global neurocognition. At the between-person level, averaged Charlson scores were examined as a predictor of neurocognitive change rate, covarying for HIV disease characteristics. Within-persons, visit-specific Charlson Index was used to predict fluctuations in global neurocognition at the same and next visit, covarying for disease measures. RESULTS Participants were 1195 PWH (mean baseline age 43·0; SD 9·7 years) followed for a mean of 7·1 years (range 0·5-20·5). At the between-person level, more rapid neurocognitive worsening correlated with higher (worse) average Charlson scores (standardized β -0·062, SE 0·015; p=0·001) and lower CD4 nadir (standardized β 0·055, SE 0·021; p=0·011), but not viral suppression or average CD4+ lymphocytes (ps > 0·05). At the within-person level, poorer visit-specific neurocognition was related to worse concurrent, but not preceding, Charlson scores (standardized β-0·046, SE 0·015; p = 0·003), detectable HIV viral load (standardized β0·018, SE 0·006; p = 0·001) and higher CD4+ (standardized β0·043, SE 0·009; p < 0·001). CONCLUSION The impact of comorbidities on neurocognitive decline exceeded that of HIV disease factors. Although correlative, the temporal relationships suggested that treatment of comorbidities might improve neurocognitive prognosis for PWH.
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Affiliation(s)
- Ronald J Ellis
- Department of Neurosciences, University of California, San Diego, San Diego, California, USA
- Department of Psychiatry, University of California, San Diego, San Diego, California, USA
| | - Emily Paolillo
- San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California, USA
| | - Rowan Saloner
- San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California, USA
| | - Robert K Heaton
- Department of Psychiatry, University of California, San Diego, San Diego, California, USA
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23
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Almeida PH, Matielo CEL, Curvelo LA, Rocco RA, Felga G, Della Guardia B, Boteon YL. Update on the management and treatment of viral hepatitis. World J Gastroenterol 2021; 27:3249-3261. [PMID: 34163109 PMCID: PMC8218370 DOI: 10.3748/wjg.v27.i23.3249] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/11/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.
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Affiliation(s)
| | - Celso E L Matielo
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Lilian A Curvelo
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Rodrigo A Rocco
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Guilherme Felga
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | | | - Yuri L Boteon
- Liver Unit, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
- Instituto Israelita de Ensino e Pesquisa Albert Einstein, Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo 05652-900, Brazil
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24
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Ellis C, Kruger HS, Viljoen M, Dave JA, Kruger MC. Factors Associated with Bone Mineral Density and Bone Resorption Markers in Postmenopausal HIV-Infected Women on Antiretroviral Therapy: A Prospective Cohort Study. Nutrients 2021; 13:nu13062090. [PMID: 34207469 PMCID: PMC8234450 DOI: 10.3390/nu13062090] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/01/2021] [Accepted: 06/10/2021] [Indexed: 12/20/2022] Open
Abstract
The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged > 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV.
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Affiliation(s)
- Christa Ellis
- Centre of Excellence for Nutrition, North-West University, Potchefstroom 2520, South Africa;
- Correspondence: ; Tel.: +27-83-374-9477
| | - Herculina S Kruger
- Centre of Excellence for Nutrition, North-West University, Potchefstroom 2520, South Africa;
- Medical Research Council Hypertension and Cardiovascular Disease Research Unit, North-West University, Potchefstroom 2520, South Africa
| | - Michelle Viljoen
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, University of the Western Cape, Bellville 7535, South Africa;
| | - Joel A Dave
- Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town 7535, South Africa;
| | - Marlena C Kruger
- School of Health Sciences, Massey University, Palmerston North 0745, New Zealand;
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25
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Katzenstein TL, Wessman M, Moseholm E, Sandholdt H, Hansen ABE, Lebech AM, Jørgensen NR, Weis N. Prevalence of low bone mineral density among people living with HIV. COGENT MEDICINE 2021. [DOI: 10.1080/2331205x.2021.1920667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Affiliation(s)
- Terese L. Katzenstein
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Maria Wessman
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Copenhagen, Denmark
| | - Ellen Moseholm
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Copenhagen, Denmark
| | - Haakon Sandholdt
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Copenhagen, Denmark
| | - Ann-Brit E Hansen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Copenhagen, Denmark
| | - Anne-Mette Lebech
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Copenhagen, Denmark
| | - Niklas R Jørgensen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Copenhagen, Denmark
| | - Nina Weis
- Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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26
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Williams ND, Huser V, Rhame F, Mayer CS, Fung KW. The changing patterns of comorbidities associated with human immunodeficiency virus infection, a longitudinal retrospective cohort study of Medicare patients. Medicine (Baltimore) 2021; 100:e25428. [PMID: 33879673 PMCID: PMC8078399 DOI: 10.1097/md.0000000000025428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 03/15/2021] [Indexed: 01/04/2023] Open
Abstract
The objective of this paper is to determine the temporal trend of the association of 66 comorbidities with human immunodeficiency virus (HIV) infection status among Medicare beneficiaries from 2000 through 2016.We harvested patient level encounter claims from a 17-year long 100% sample of Medicare records. We used the chronic conditions warehouse comorbidity flags to determine HIV infection status and presence of comorbidities. We prepared 1 data set per year for analysis. Our 17 study data sets are retrospective annualized patient level case histories where the comorbidity status reflects if the patient has ever met the comorbidity case definition from the start of the study to the analysis year.We implemented one logistic binary regression model per study year to discover the maximum likelihood estimate (MLE) of a comorbidity belonging to our binary classes of HIV+ or HIV- study populations. We report MLE and odds ratios by comorbidity and year.Of the 66 assessed comorbidities, 35 remained associated with HIV- across all model years, 19 remained associated with HIV+ across all model years. Three comorbidities changed association from HIV+ to HIV- and 9 comorbidities changed association from HIV- to HIV+.The prevalence of comorbidities associated with HIV infection changed over time due to clinical, social, and epidemiological reasons. Comorbidity surveillance can provide important insights into the understanding and management of HIV infection and its consequences.
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Affiliation(s)
- Nick D. Williams
- The Lister Hill National Center for Biomedical Communications at the National Library of Medicine, National Institutes of Health in the United States, Bethesda, Maryland
| | - Vojtech Huser
- The Lister Hill National Center for Biomedical Communications at the National Library of Medicine, National Institutes of Health in the United States, Bethesda, Maryland
| | - Frank Rhame
- Division of Infectious Diseases and International Medicine at the University of Minnesota School of Medicine, Minnesota
| | - Craig S. Mayer
- The Lister Hill National Center for Biomedical Communications at the National Library of Medicine, National Institutes of Health in the United States, Bethesda, Maryland
| | - Kin Wah Fung
- The Lister Hill National Center for Biomedical Communications at the National Library of Medicine, National Institutes of Health in the United States, Bethesda, Maryland
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27
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Anderson SJ, Hsu CY, Ou HT, Ko NY, Yang CT, Lopes S. Cost-Effectiveness of Juluca for Human Immunodeficiency Virus Infection Treatment in Virologically Suppressed Adults in Taiwan. Value Health Reg Issues 2021; 24:216-223. [PMID: 33857719 DOI: 10.1016/j.vhri.2020.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 10/08/2020] [Accepted: 11/12/2020] [Indexed: 10/21/2022]
Abstract
OBJECTIVES Although the efficacy of traditional 3-drug regimens for the treatment of HIV is well established, tolerability and toxicity concerns remain. New 2-drug regimens such as Juluca (dolutegravir [DTG]/rilpivirine [RPV]) offer noninferior efficacy versus 3-drug regimens (SWORD-1 and SWORD-2 studies), while reducing cumulative drug exposure and potentially long-term toxicities and drug-drug interactions. Here, we assess the cost-effectiveness of DTG/RPV for the treatment of HIV-1 for virologically suppressed adults in Taiwan. METHODS A hybrid decision tree and Markov cohort state transition model was used to evaluate the expected economic costs and clinical outcomes associated with DTG/RPV and comparators. Model health states were defined by viral load and CD4 cell count. Efficacy and safety data were informed from SWORD-1 and SWORD-2 studies and the literature. The risk of long-term toxicities (cardiovascular disease, bone fractures, and chronic kidney disease) were included. Current branded drug acquisition prices were included, and healthcare costs informed by a bespoke costing study using National Health Insurance Research Database data. Incremental cost-effectiveness ratios were calculated and compared with a willingness-to-pay threshold of 2 times Taiwan's gross domestic product (NT$1 550 000). RESULTS DTG/RPV was found to be a cost-saving regimen compared to 3 comparators (rilpivirine [RPV]/emtricitabine [FTC]/tenofovir disoproxil fumarate [TDF], dolutegravir [DTG]/abacavir [ABC]/lamivudine [3TC], and elvitegravir [EVG]/cobicistat [c]/emtricitabine [FTC]/tenofovir alafenamide [TAF]) and fell in the southwest quadrant of the cost-effectiveness plane where it is generating significant savings with a small decrement in lifetime quality-adjusted life-years (-0.005). It was, however, more expensive than efavirenz [EFV]/emtricitabine [FTC]/ tenofovir disoproxil fumarate [TDF]. CONCLUSIONS DTG/RPV is cost-saving compared to RPV/FTC/TDF, DTG/ABC/3TC, and EVG/c/FTC/TAF, and provides comparable efficacy with reduced cumulative drug exposure.
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Affiliation(s)
| | | | - Huang-Tz Ou
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Taiwan; Department of Pharmacy, National Cheng Kung University, Taiwan
| | - Nai-Ying Ko
- Department of Nursing, National Cheng Kung University, Taiwan
| | - Chun-Ting Yang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Taiwan
| | - Sara Lopes
- Global Health Outcomes, ViiV Healthcare, Brentford, UK
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28
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Łomiak M, Stępnicki J, Mikuła T, Wiercińska-Drapało A. Weight and body mass index increase after switch from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate-containing treatment in an antiretroviral therapy-experienced group. Int J STD AIDS 2021; 32:570-577. [PMID: 33612018 DOI: 10.1177/0956462420983699] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Tenofovir alafenamide fumarate (TAF) is an alternative to tenofovir disoproxil fumarate (TDF). Currently, TAF is increasingly being used because of its non-inferior antiviral properties, lower risk of nephrotoxicity, and lower decrease in bone mineral density than TDF. There is growing evidence of unfavorable effects of TAF on weight and body mass index (BMI) in antiretroviral therapy (ART)-experienced patients treated with TAF-based ART. The aim of this study was to evaluate whether switching from TDF-containing to TAF-containing ART is associated with an increase in BMI and body weight in ART-experienced patients. Two study groups were established: 32 patients who switched from TDF to TAF only and 68 patients who switched from TDF to TAF along with changes to other components of the ART regimen. Significant weight gain and BMI increase was observed during the first year after initiation of TAF-containing ART regimens in both groups (mean change +1.91 kg and +0.61 kg/m2 in the first group and +1.50 kg and +0.49 kg/m2 in the second group). During the second year of TAF-based treatment, a sustained trend of body weight and BMI increase was noted only in the second group (mean change +1.46 kg, + 0.46 kg/m2). Analysis of body weight changes in certain subpopulations from the second group (selected based on patients' baseline characteristics) revealed a significant weight gain within two years after the switch in patients over 50 years old and in those whose ART had lasted longer than 10 years. These findings suggest that a possible impact of TAF on weight gain should be taken into account when selecting ART components, especially in older patients or those with a long history of antiretroviral treatment.
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Affiliation(s)
- Michał Łomiak
- Students Science Society of the Department of Infectious and Tropical Diseases and Hepatology, 162259Medical University of Warsaw, Poland
| | - Jan Stępnicki
- Students Science Society of the Department of Infectious and Tropical Diseases and Hepatology, 162259Medical University of Warsaw, Poland
| | - Tomasz Mikuła
- Department of Infectious and Tropical Diseases and Hepatology, 162259Medical University of Warsaw, Poland
| | - Alicja Wiercińska-Drapało
- Department of Infectious and Tropical Diseases and Hepatology, 162259Medical University of Warsaw, Poland
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29
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Mwaka ES, Munabi IG, Castelnuovo B, Kaimal A, Kasozi W, Kambugu A, Musoke P, Katabira E. Low bone mass in people living with HIV on long-term anti-retroviral therapy: A single center study in Uganda. PLoS One 2021; 16:e0246389. [PMID: 33544754 PMCID: PMC7864439 DOI: 10.1371/journal.pone.0246389] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 01/15/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND This study set out to determine the prevalence of low bone mass following long-term exposure to antiretroviral therapy in Ugandan people living with HIV. METHODS A cross-sectional study was conducted among 199 people living with HIV that had been on anti-retroviral therapy for at least 10 years. All participants had dual X-ray absorptiometry to determine their bone mineral density. The data collected included antiretroviral drug history and behavioral risk data Descriptive statistics were used to summarize the data. Inferential statistics were analyzed using multilevel binomial longitudinal Markov chain Monte Carlo mixed multivariate regression modelling using the rstanarm package. RESULTS One hundred ninety nine adults were enrolled with equal representation of males and females. The mean age was 39.5 (SD 8.5) years. Mean durations on anti-retroviral treatment was 12.1 (SD 1.44) years, CD4 cell count was 563.9 cells/mm3. 178 (89.5%) had viral suppression with <50 viral copies/ml. There were 4 (2.0%) and 36 (18%) participants with low bone mass of the hip and lumbar spine respectively. Each unit increase in body mass index was associated with a significant reduction in the odds for low bone mineral density of the hip and lumbar spine. The duration on and exposure to the various antiretroviral medications had no significant effect on the participant's odds for developing low bone mass. All the coefficients of the variables in a multivariable model for either hip or lumbar spine bone mass were not significant. CONCLUSION These results provide additional evidence that patients on long term ART achieve bone mass stabilization. Maintaining adequate body weight is important in maintaining good bone health in people on antiretroviral therapy.
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Affiliation(s)
- Erisa Sabakaki Mwaka
- School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Ian Guyton Munabi
- School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Barbara Castelnuovo
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Arvind Kaimal
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
| | - William Kasozi
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Andrew Kambugu
- School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Philippa Musoke
- Department of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Elly Katabira
- Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
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Guo F, Song X, Li Y, Guan W, Pan W, Yu W, Li T, Hsieh E. Longitudinal change in bone mineral density among Chinese individuals with HIV after initiation of antiretroviral therapy. Osteoporos Int 2021; 32:321-332. [PMID: 32803316 PMCID: PMC9509525 DOI: 10.1007/s00198-020-05584-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 08/03/2020] [Indexed: 01/05/2023]
Abstract
UNLABELLED This is the first study to report changes in BMD and related risk factors among Chinese patients with HIV after initiation of tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy. Greater bone mineral density (BMD) loss was observed in patients treated with TDF, compared to those on non-TDF-containing regimens. Our findings provide important knowledge regarding the risk factors in the long-term clinical management of patients with HIV in China. INTRODUCTION Persons living with HIV (PLWH) are at increased risk for osteoporosis and fracture. Tenofovir disoproxil fumarate (TDF) has been associated with higher rates of bone mineral density (BMD) loss, osteoporosis, and fracture. Few studies have studied the impact among PLWH in Asia. METHODS We analyzed retrospectively patients from the outpatient HIV clinic of a large tertiary hospital in Beijing, China, from March 2007 to May 2016. Patients who had dual-energy X-ray absorptiometry testing prior to antiretroviral initiation and at 48 and/or 96 weeks after initiation were included in this analysis. RESULTS A total of 136 patients were included (mean age 36.0 ± 10.6 years) and over 90% participants were male and Han Chinese ethnicity. We observed greater declines in BMD at the spine from baseline to week 48 (-2.94% vs. -0.74%) and at the hip from baseline to week 96 (-4.37% vs. -2.34%) in the TDF group compared with the non-TDF group. With regard to HIV-specific parameters, longer duration since HIV diagnosis and undetectable viral load over time were associated with lower BMD at the hip [relative risk (RR) 0.97, 95% confidence index (CI) (0.95, 0.99) per 1 year increase and RR 0.96, 95%CI (0.94, 0.99), respectively] and femoral neck [RR 0.97, 95%CI (0.95, 0.99) per 1 year increase and RR 0.97, 95%CI (0.95, 0.998), respectively] over 96 weeks. CONCLUSIONS This is the first study to report changes in BMD among PLWH after initiation of TDF-based antiretroviral therapy in China. Our findings provide important knowledge for the long-term clinical management of PLWH from this region.
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Affiliation(s)
- F Guo
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - X Song
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - Y Li
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - W Guan
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - W Pan
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China
| | - W Yu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - T Li
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.
- Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - E Hsieh
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.
- Section of Rheumatology, Allergy, and Clinical Immunology, Yale School of Medicine, 300 Cedar Street, TAC S-525, PO Box 208031, New Haven, CT, 06517, USA.
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Lim N, Jackson S, Engler C, Lake JR. The Impact of Tenofovir Disoproxil Fumarate on Reduced Bone Mineral Density and Fractures in Liver Transplant Recipients. Transplant Proc 2020; 53:215-220. [PMID: 33139039 DOI: 10.1016/j.transproceed.2020.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 09/02/2020] [Accepted: 09/18/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) is associated with reduced bone density in patients with human immunodeficiency virus, but the effect of TDF on bone density in liver transplant (LT) recipients is unknown. METHODS We performed a single-center, retrospective study of LT recipients with hepatitis B taking TDF compared to a control group with non-hepatitis B virus viral hepatitis. The primary outcome was reduced bone density, defined as femoral neck or lumbar T-score less than -1. Other outcomes included mean T-score and fractures. RESULTS Three hundred ninety-three patients were studied: 52 patients in the TDF group and 341 patients in the control group; 64.3% patients in the TDF group had reduced bone density vs 71.4% in the control group (P = .58) before LT, compared to 75% and 81.5% (P = .57), respectively, after LT. Mean posttransplant lumbar T-scores were lower in the TDF group (-1.74 vs -0.75, P = .04). There was no difference between the 2 groups for the other outcomes. In a multivariate Cox proportional hazards model, TDF use did not affect the risk of post-LT reduced bone density (hazard ratio = 0.99; 95% confidence interval, 0.56-1.76; P = .97). CONCLUSION TDF use was not associated with reduced bone mineral density or increased rates of fractures in LT recipients compared to controls in this study.
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Affiliation(s)
- N Lim
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota.
| | - S Jackson
- Fairview Health Services, Minneapolis, Minnesota
| | - C Engler
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota
| | - J R Lake
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota
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Atypical femoral neck stress fracture in a human immunodeficiency virus-infected patient despite anti-osteoporotic treatment: A case report. Turk J Phys Med Rehabil 2020; 66:364-367. [PMID: 33089094 PMCID: PMC7557631 DOI: 10.5606/tftrd.2020.4286] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 05/15/2019] [Indexed: 11/21/2022] Open
Abstract
Both human immunodeficiency virus (HIV) infection and antiretroviral therapy are related to an increased risk of fracture. As a result of the developments in HIV treatment in recent years, life expectancy in HIV-infected patients has increased. Therefore, HIV-related musculoskeletal problems such as osteoporosis and avascular necrosis are more common currently. There are complex mechanisms in HIV-related osteoporosis. The loss of bone mineral density is particularly distinctive in the first months of the therapy. In this report, we present a 54-year-old woman admitted to our clinic with right thigh pain for three months and diagnosed with a femoral neck stress fracture.
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Oster Y, Cohen MJ, Dresner-Pollak R, Szalat A, Elinav H. Increase in bone turnover markers in HIV patients treated with tenofovir disoproxil fumarate combined with raltegravir or efavirenz. Bone Rep 2020; 13:100727. [PMID: 33163587 PMCID: PMC7607241 DOI: 10.1016/j.bonr.2020.100727] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 09/30/2020] [Accepted: 10/12/2020] [Indexed: 12/02/2022] Open
Abstract
Introduction Accelerated bone loss and osteoporosis are multifactorial comorbidities related to HIV and its treatments; however, their mechanisms remain elusive. Identifying HIV treatments that are differentially linked to osteoporosis risk, and clinical factors associated with HIV-related osteoporosis may enable optimizing anti-retroviral treatment (ART) and anti-osteoporosis therapy in preventing or treating this debilitating complication. This study aims to evaluate the dynamics of bone turnover markers after initiation of two commonly used antiretroviral regimens. Methods A prospective matched cohort study. Thirty treatment-naïve male patients (mean age 40 ± 10y) who initiated treatment with truvada (tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)) + raltegravir or TDF/FTC + efavirenz were included in the study. Control group included 15 treatment-naive HIV patients. Serum morning fasting level of P1NP and CTX were measured 0, 1, 6, and 12 months after treatment initiation in the two study groups, and at 0, 6 and 12 months in the control group. Results In both treatment groups, but not in the control group, both markers increased significantly over time with no difference in BTM between patients treated with raltegravir or efavirenz. Levels of P1NP were statistically higher at 6 and 12 months after treatment initiation in both treatment groups compared to the controls, while CTX during treatment increased in both treatment groups but was significantly higher only in the raltegravir treatment group after 12 months. The ratio of area under the curve of P1NP/CTX correlated with CD4 increment. Conclusions Treatment initiation with raltegravir or efavirenz combined with TDF/FTC is associated with increased bone turnover. Thus, therapy that optimize bone turnover is needed to reduce bone loss at this vulnerable period and improve long-term bone health.
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Affiliation(s)
- Yonatan Oster
- Hadassah AIDS Center, Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Matan J Cohen
- Clalit Health Services, Jerusalem District, affiliated with the School of Medicine, Hebrew University, Jerusalem, Israel
| | - Rivka Dresner-Pollak
- The Department of Endocrinology and Metabolism, Division of Internal Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Auryan Szalat
- Department of Medicine, Endocrinology and Metabolism Service, Hadassah Hebrew, University Medical Center, Jerusalem, Israel
| | - Hila Elinav
- Hadassah AIDS Center, Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel
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Sutton SS, Magagnoli J, Hardin JW, Hsu LI, Beaubrun A, Majethia S, Cummings TH. Association of tenofovir disoproxil fumarate exposure with chronic kidney disease and osteoporotic fracture in US veterans with HIV. Curr Med Res Opin 2020; 36:1635-1642. [PMID: 32856940 DOI: 10.1080/03007995.2020.1816538] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF)-based regimens have been associated with impaired kidney function and loss of bone mineral density among patients living with HIV (PLWH). We assess the association between TDF exposure and the odds of chronic kidney disease (CKD) and osteoporotic fracture in HIV patients. METHODS Demographics, administrative claims, and pharmacy dispensation were extracted from the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Patients were categorized based on TDF utilization. Incidence rates for patients exposed and unexposed to TDF were calculated per 1000 patient-years (PYs). Logistic regression was used to calculate the odds of outcome after adjusting for baseline and clinical characteristics. RESULTS The sample included 4,630 PLWH who were currently exposed to TDF and 1,181 who were never exposed to TDF for the CKD analyses. For fracture analyses, the sample included 6,883 PLWH who were currently exposed to TDF and 1,951 who were never exposed to TDF. In adjusted models, current TDF exposure was associated with increased odds of CKD compared to never having been exposed (OR: 1.48, 95% CI: 1.18-1.85). Odds of fracture were 2.32 times higher for patients who were currently on a TDF regimen (OR: 2.32, 95% CI: 1.58-3.42) compared to those who had never been exposed to TDF in adjusted models. CONCLUSIONS In a large cohort of US veterans with HIV, current exposure to TDF was associated with a 48% higher odds of CKD and a greater than two-fold increase in the odds of osteoporotic fracture.
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Affiliation(s)
- S Scott Sutton
- Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA
- WJB Dorn Veterans Affairs Medical Center, Dorn Research Institute, Columbia, SC, USA
| | - Joseph Magagnoli
- Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA
- WJB Dorn Veterans Affairs Medical Center, Dorn Research Institute, Columbia, SC, USA
| | - James W Hardin
- WJB Dorn Veterans Affairs Medical Center, Dorn Research Institute, Columbia, SC, USA
- Department of Epidemiology and Biostatistics, Norman J. Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Ling-I Hsu
- Gilead Sciences Inc., Foster City, CA, USA
| | | | | | - Tammy H Cummings
- Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA
- WJB Dorn Veterans Affairs Medical Center, Dorn Research Institute, Columbia, SC, USA
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Jacobson DL, Yu W, Hazra R, Brummel S, Geffner ME, Patel K, Borkowsky W, Wang J, Chen JS, Mirza A, DiMeglio LA. Fractures in children and adolescents living with perinatally acquired HIV. Bone 2020; 139:115515. [PMID: 32619695 PMCID: PMC7484335 DOI: 10.1016/j.bone.2020.115515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 06/28/2020] [Accepted: 06/28/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Across numerous settings, bone mineral density for age and sex is lower in children/adolescents living with perinatally-acquired HIV (PHIV) compared to uninfected peers. We assessed incidences of any fracture/any long bone fracture, and osteoporosis prevalence in PHIV and HIV-exposed uninfected (PHEU) participants in the Pediatric HIV/AIDS Cohort Study (PHACS). METHODOLOGY Lifetime history of fracture events from birth up to age 20 years was obtained by chart review and/or interview, including age at fracture, mechanism, and bone(s) fractured. Poisson regression models were fit comparing fracture incidence by HIV status adjusted for age, sex, and race, with effect modification by age (<6, ≥6 yr). RESULTS PHIV (N = 412) were older (median 17.5 vs 16.7 yr) and more frequently reported black race (72% vs 61%) than PHEU children/adolescents (N = 206). 17% of PHIV and 12% of PHEU ever reported a fracture. Among children <6 yr, the adjusted incidence rate ratio of ≥1 fracture was higher (7.23; 95% CI 0.98, 53.51) in PHIV than PHEU, but similar among children/adolescents ≥6 years (1.20; 95% CI: 0.77, 1.87). Results were similar for long bone fracture. The most common fracture mechanisms were falling to the ground from a standing height (23.6% PHIV vs 8.8% PHEU) and sports injuries (21.3% vs 32.4%), and the most commonly fractured sites were the forearm and small bones of the wrist/hands. None of the children had osteoporosis. CONCLUSIONS Among children/adolescents ≥6 yr of age, fractures were similar by perinatal HIV status. Prospective, targeted collection of fracture history will be necessary to determine rates of fracture as PHIV and PHEU age into adulthood. SUMMARY Lifetime fracture history was collected in children/adolescents living with perinatally-acquired HIV (PHIV) and HIV-exposed uninfected (PHEU) children from birth up to age 20 years. Fracture incidence was higher in PHIV compared to PHEU among children <6 years old, but not among older children/adolescents.
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Affiliation(s)
- Denise L Jacobson
- Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, USA.
| | - Wendy Yu
- Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, USA
| | - Rohan Hazra
- Maternal and Pediatric Infectious Diseases Branch, Division of Extramural Research, Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health, Department of Health and Human Services, Bethesda, USA
| | - Sean Brummel
- Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, USA
| | - Mitchell E Geffner
- The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, USA
| | - Kunjal Patel
- Department of Epidemiology and Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, USA
| | | | - Jiajia Wang
- Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, USA
| | - Janet S Chen
- Department of Pediatrics, Drexel University College of Medicine, Philadelphia, USA
| | - Ayesha Mirza
- Department of Pediatrics, University of Florida College of Medicine, Jacksonville, USA
| | - Linda A DiMeglio
- Department of Pediatrics, Division of Pediatric Endocrinology/Diabetology and Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA.
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Ibrahim F, Samarawickrama A, Hamzah L, Vincent R, Gilleece Y, Waters L, Kegg S, Barbini B, Campbell L, Post FA. Bone mineral density, kidney function, weight gain and insulin resistance in women who switch from TDF/FTC/NNRTI to ABC/3TC/DTG. HIV Med 2020; 22:83-91. [PMID: 32985122 DOI: 10.1111/hiv.12961] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2020] [Indexed: 01/13/2023]
Abstract
OBJECTIVES Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). METHODS We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual-energy X-ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. RESULTS In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479-800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new-onset metabolic syndrome. CONCLUSIONS Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings.
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Affiliation(s)
| | | | - L Hamzah
- St George's Healthcare NHS Trust, London, UK
| | - R Vincent
- North Middlesex University Hospital, London, UK
| | - Y Gilleece
- Brighton and Sussex University Hospitals, Brighton, UK
| | - L Waters
- Mortimer Market Centre, London, UK
| | - S Kegg
- Lewisham and Greenwich NHS Trust, London, UK
| | - B Barbini
- King's College Hospital NHS Foundation Trust, London, UK
| | - L Campbell
- King's College London, London, UK.,King's College Hospital NHS Foundation Trust, London, UK
| | - F A Post
- King's College London, London, UK.,King's College Hospital NHS Foundation Trust, London, UK
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Li M, Zhou L, Dorsey HG, Musoff C, Jnr DA, Schoen N, Djan K, Paintsil E. Tenofovir alafenamide does not inhibit mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line. Antiviral Res 2020; 183:104948. [PMID: 32980447 DOI: 10.1016/j.antiviral.2020.104948] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 09/18/2020] [Accepted: 09/19/2020] [Indexed: 01/11/2023]
Abstract
In clinical trials, the concentration of tenofovir diphosphate (TFV-DP) in peripheral mononuclear cells was 4 to 5-fold higher in individuals treated with tenofovir alafenamide (TAF) compared to individuals treated with tenofovir disoproxil fumarate (TDF). We hypothesized that the higher intracellular accumulation of TFV-DP could cause mitochondrial toxicity from either polymerase gamma (Pol-γ)-dependent or Pol-γ-independent mechanism(s). To test this hypothesis, we cultured human T lymphoblastoid cell line (CEM cells) for up to 12 days with TAF or TDF (multiplicities of Cmax) to investigate the effects on mitochondrial function and respiration, and cholesterol biosynthesis. Both TAF and TDF treatments had no significant effect on cell growth, mitochondrial potential (ΔΨ), production of reactive oxygen species (ROS), and mitochondrial respiratory parameters. TAF had no statistically significant effect on expression of Pol-γ mRNA, mitochondria DNA (mtDNA) content, expression of proteins of the electron transport chain (ETC), and key genes of cholesterol biosynthesis. TDF had significant reduction in mtDNA content at 8xCmax, and statistically significant reduction in mRNA expression of squalene epoxidase (SQLE). Our findings do not support our hypothesis that the higher intracellular accumulation of TFV-DP in cells treated with TAF could cause mitochondrial dysfunction. In conclusion, our findings add to the emerging data that TAF may have a low potential for causing mitochondrial toxicity in HIV-infected individuals on TAF-containing regimens.
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Affiliation(s)
- Min Li
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Lei Zhou
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Harold G Dorsey
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Charles Musoff
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Dereck Amakye Jnr
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Natalie Schoen
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Kweku Djan
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Elijah Paintsil
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA; Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA; Department of Epidemiology & Public Health, Yale School of Public Health, New Haven, CT, USA.
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Abstract
PLHIV have an increased risk of osteoporosis and fractures when compared with people of the same age and sex. In this review, we address the epidemiology and the pathophysiology of bone disease and fractures in PLHIV. The assessment of fracture risk and fracture prevention in these subjects is also discussed. The spectrum of HIV-associated disease has changed dramatically since the introduction of potent antiretroviral drugs. Today, the survival of people living with HIV (PLHIV) is close to that of the general population. However, the longer life-span in PLHIV is accompanied by an increased prevalence of chronic diseases. Detrimental effects on bone health are well recognised, with an increased risk of osteoporosis and fractures, including vertebral fractures, compared to the general population. The causes of bone disease in PLHIV are not fully understood, but include HIV-specific risk factors such as use of antiretrovirals and the presence of chronic inflammation, as well as traditional risk factors for fracture. Current guidelines recommend the use of FRAX to assess fracture probability in PLHIV age ≥ 40 years and measurement of bone mineral density in those at increased fracture risk. Vitamin D deficiency, if present, should be treated. Bisphosphonates have been shown to increase bone density in PLHIV although fracture outcomes are not available.
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Affiliation(s)
- M O Premaor
- Department of Clinical Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
| | - J E Compston
- Department of Medicine, Cambridge Biomedical Campus, Cambridge, UK
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Pramukti I, Liu HY, Chen CC, Chen YC, Yeh CY, Fetzer S, Ibrahim K, Tai TW, Ko WC, Ko NY. HCV co-infection among people living with HIV Is associated with Higher fracture risk. J Infect Public Health 2020; 13:1724-1728. [PMID: 32653478 DOI: 10.1016/j.jiph.2020.06.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/21/2020] [Accepted: 06/14/2020] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION The purpose of this study was to predict the 10-year risk of fracture among people living with HIV (PLWH) using FRAX™, and to determine the risk factors related to a high probability of fractures. METHODOLOGY This study consisted of 288 subjects aged 40 years and above. The ten-year probability of major osteoporotic fractures (MOF) and hip fractures was assessed using the FRAX™ algorithm with bone mineral density (BMD) data. A logistic regression was used to determine risk factors related to a high probability of major osteoporotic fracture and hip fracture. RESULTS The median 10-year probability of fracture was 3.7% (IQR 2.2-6.2) for MOF and 0.8% (IQR 0.3-2.5) for hip fractures. In addition to old age, previous fracture history, and low T-scores, HCV co-infection was associated with a higher risk of hip fractures in PLWH (AOR: 4.3, 95% CI: 1.29-14.33). Old age and low T-scores were also associated with a high probability of MOF. CONCLUSIONS HCV co-infection among PLWH is associated with a higher risk of hip fracture. Sustained efforts in terms of pharmacologic and non-pharmacologic interventions in PLWH are necessary to prevent osteoporotic fractures, especially in those with HCV co-infections.
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Affiliation(s)
- Iqbal Pramukti
- Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Faculty of Nursing, Universitas Padjadjaran, West Java, Indonesia
| | - Hsiao-Ying Liu
- Department of Nursing, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chang-Chun Chen
- Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Chin Chen
- Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Nursing, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chun-Yin Yeh
- Department of Computer Science and Information Engineering, National Cheng Kung University, Taiwan
| | - Susan Fetzer
- Southern New Hampshire Medical Center, Nashua, New Hampshire, USA
| | - Kusman Ibrahim
- Faculty of Nursing, Universitas Padjadjaran, West Java, Indonesia
| | - Ta-Wei Tai
- Departments of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Wen-Chien Ko
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Nai-Ying Ko
- Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Nursing, National Cheng Kung University Hospital, Tainan, Taiwan.
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40
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Pramukti I, Lindayani L, Chen YC, Yeh CY, Tai TW, Fetzer S, Ko NY. Bone fracture among people living with HIV: A systematic review and meta-regression of prevalence, incidence, and risk factors. PLoS One 2020; 15:e0233501. [PMID: 32497105 PMCID: PMC7271989 DOI: 10.1371/journal.pone.0233501] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 05/06/2020] [Indexed: 02/06/2023] Open
Abstract
Introduction People living with HIV (PLWH) had a higher prevalence and incidence rate of bone fracture compared to general population. Although several studies have explored this phenomenon, the prevalence and incidence rate of fracture were varied. Objective The aim of the study is to determine and analyze the pooled prevalence, incidence rate of fracture and fracture risk factors among people living with HIV (PLWH). Methods PubMed, Cochrane Library, CINAHL with full Text, and Medline databases for studies published up to August 2019 were searched. Studies reporting the prevalence or incidence of fracture among PLWH were included. Study quality was assessed using the Joanna Briggs Institute (JBI) appraisal tool. A meta-analysis with random-effects model was performed to determine pooled estimates of prevalence and incidence rates of fracture. A meta-regression was performed to determine the source of heterogeneity. Results The pooled estimated prevalence of fracture among PLWH was 6.6% (95% CI: 3.8–11.1) with pooled odds ratio of 1.9 (95%CI: 1.1–3.2) compared to the general population. The pooled estimates of fracture incidence were 11.3 per 1000 person-years (95% CI: 7.9–14.5) with incidence rate ratio (IRR) of 1.5 (95% CI: 1.3–1.8) compared to the general population. Risk factors for fracture incidence were older age (aHR 1.4, 95% CI: 1.3–1.6), smoking (aHR 1.3, 95% CI: 1.1–1.5), HIV/HCV co-infection (aHR 1.6, 95% CI: 1.3–1.9), and osteoporosis (aHR 3.3, 95% CI: 2.2–5.1). Conclusions Our finding highlights a higher risk of fracture among PLWH compared to the general population. Osteoporosis, smoking and HIV/HCV coinfection as the significant modifiable risk factors should be prioritized by the HIV health providers when care for PLWH.
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Affiliation(s)
- Iqbal Pramukti
- Department of Nursing, International Doctoral Program in Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Faculty of Nursing, Universitas Padjadjaran, West Java, Indonesia
| | - Linlin Lindayani
- Sekolah Tinggi Ilmu Keperawatan PPNI Jawa Barat, Bandung, Indonesia
| | - Yen-Chin Chen
- Department of Nursing, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chun-Yin Yeh
- Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Ta-Wei Tai
- Departments of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Susan Fetzer
- Southern New Hampshire Medical Center, Nashua, New Hampshire, United States of America
| | - Nai-Ying Ko
- Department of Nursing, International Doctoral Program in Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Nursing, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- * E-mail:
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Joly V, Burdet C, Landman R, Vigan M, Charpentier C, Katlama C, Cabié A, Benalycherif A, Peytavin G, Yeni P, Mentre F, Argoud AL, Amri I, Descamps D, Yazdanpanah Y. Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL). J Antimicrob Chemother 2020; 74:739-745. [PMID: 30476165 DOI: 10.1093/jac/dky467] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 09/27/2018] [Accepted: 10/02/2018] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVES To evaluate the dolutegravir+lamivudine combination in virologically suppressed patients living with HIV. METHODS The ANRS 167 LAMIDOL trial was an open-label, single arm, multicentre trial assessing once-daily dolutegravir (50 mg)+lamivudine (300 mg) in virologically suppressed HIV-1 patients on first-line triple-drug regimens. The main criteria for inclusion in the trial were plasma viral load (pVL) ≤50 copies/mL for ≥2 years, CD4 nadir >200 cells/mm3 and WT HIV prior to treatment initiation. From week -8 (W-8) to day 0 (D0) (Phase 1), the current third agent was switched to dolutegravir. From D0 to W48 (Phase 2), patients received once-daily dolutegravir+lamivudine, except if intolerant or if pVL >50 copies/mL during Phase 1. Virological failure was defined as pVL >50 copies/mL in two consecutive samples. The study was designed to show that the strategy had an efficacy of ≥80%, assuming a 90% success rate with a type I error of 5% and a power of 90%. RESULTS In total, 104 of 110 patients enrolled in Phase 1 were included in Phase 2. These 104 patients were 86% male, 72% MSM and 87% CDC stage A. Their characteristics were (median): age 45 years, CD4 nadir 339 cells/mm3, baseline CD4 743 cells/mm3 and duration of viral suppression 4.5 years. The overall success rate at W48 was 97% (95% CI: 94%-100%), meeting the design expectation/assumption. Three therapeutic failures occurred: one virological failure at W4, one lost to follow-up at W32 and one interruption of therapeutic strategy at W40 after a blip (pVL 59 copies/mL but control pVL <50 copies/mL). Three viral blips occurred in two additional patients. Neither M184V nor integrase resistance mutations were detected after failure or blips. CONCLUSIONS Dolutegravir+lamivudine is a promising maintenance therapy in HIV-1-infected patients with controlled virological suppression.
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Affiliation(s)
- Véronique Joly
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, SMIT, Hôpital Bichat, AP-HP, Paris, France
| | - Charles Burdet
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Département d'épidémiologie, Biostatistique et Recherche Clinique, Hôpital Bichat, AP-HP, Paris, France
| | | | - Marie Vigan
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Département d'épidémiologie, Biostatistique et Recherche Clinique, Hôpital Bichat, AP-HP, Paris, France
| | - Charlotte Charpentier
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France
| | | | - André Cabié
- CIC1424 INSERM, Université des Antilles, SMIT, CHU de Martinique, Fort de France, France
| | | | - Gilles Peytavin
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Laboratoire de Pharmacologie-Toxicologie, Hôpital Bichat, AP-HP, Paris, France
| | - Patrick Yeni
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, SMIT, Hôpital Bichat, AP-HP, Paris, France
| | - France Mentre
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Département d'épidémiologie, Biostatistique et Recherche Clinique, Hôpital Bichat, AP-HP, Paris, France
| | - Anne-Laure Argoud
- French Agency for Research on AIDS and Viral Hepatitis, Paris, France
| | - Imane Amri
- French Agency for Research on AIDS and Viral Hepatitis, Paris, France
| | - Diane Descamps
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France
| | - Yazdan Yazdanpanah
- IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, SMIT, Hôpital Bichat, AP-HP, Paris, France
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Bhatta M, Nandi S, Dutta N, Dutta S, Saha MK. HIV Care Among Elderly Population: Systematic Review and Meta-Analysis. AIDS Res Hum Retroviruses 2020; 36:475-489. [PMID: 32027170 DOI: 10.1089/aid.2019.0098] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Elderly people living with HIV are increasing. At present in the United States, nearly half of newly diagnosed HIV-infected people are aged >50 years. Diagnosis and treatment of HIV-infected elderly patients tends to be delayed by several health care factors as several life-threatening diseases are common in elderly people. This study aimed to find the pooled HIV prevalence in elderly population and the present situation of continuum care for the elderly HIV patients through systematic review and meta-analysis. All previously published articles from 2000 to 2018 are retrieved using MEDLINE, PUBMED, Cochrane Library, EMBASE, and Google Scholar. DerSimonian and Laird Random Effects model are used to critically appraise articles. STATA 13.0 is used to perform the meta-analysis and quantum-geographic information system (Q-GIS) is used to prepare desired map. I2 statistics has been used to test heterogeneity and publication biases. Results have been presented using forest plots. A total of 28 studies are included in this meta-analysis. Present analysis revealed pooled prevalence of HIV in elderly population as 15.79% with a lower rate of viral suppression as 11.524% (95% confidence interval, CI: 11.199-11.855), where a moderate number 38.643% (95% CI: 38.289-38.997) of elderly patients received antiretroviral therapy (ART) globally. The ART retention rate was 12.769% (95% CI: 12.540-13.001) with 6.15% (95% CI: 6.089-6.212) mortality. Despite successful administration of ART in developing part of the world that have relatively higher retention rates among HIV-infected elderly patients only a small percentage are virally suppressed, largely due to elderly drugs interact with ART and several comorbidities reduce the life span of the elderly people.
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Affiliation(s)
- Mihir Bhatta
- Divisions of Virology and ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Srijita Nandi
- Divisions of Virology and ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Nalok Dutta
- Divisions of Virology and ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Shanta Dutta
- Divisions of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
| | - Malay Kumar Saha
- Divisions of Virology and ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, India
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Shafran SD, Di Perri G, Esser S, Lelièvre JD, Parczewski M. Planning HIV therapy to prevent future comorbidities: patient years for tenofovir alafenamide. HIV Med 2020; 20 Suppl 7:1-16. [PMID: 31099116 DOI: 10.1111/hiv.12755] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2019] [Indexed: 11/28/2022]
Abstract
Since the introduction of suppressive antiretroviral therapy (ART), HIV has become a chronic disease, with infected people in high-income countries approaching similar life expectancy to the general population. As this population ages, an increasing number of people with HIV are living with age-, treatment-, and disease-related comorbidities. Lifestyle factors such as smoking, alcohol abuse, and substance misuse have a role in age-related comorbidity. Some degree of immune dysfunction is suggested by the presence of markers of immune activation/inflammation despite effective suppression of HIV replication. Cumulative exposure to some antiretroviral drugs contributes to HIV-associated comorbidities, with risk increasing with age. Specifically, tenofovir disoproxil fumarate (TDF), ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir are associated with renal impairment, and TDF is known to cause loss of bone mineral density. Tenofovir alafenamide (TAF) was developed to improve on the safety profile of TDF, while maintaining its efficacy. TAF has better stability in plasma, and higher intracellular accumulation of tenofovir diphosphate in target cells, which has resulted in improved antiviral activity at lower doses with improved renal and bone safety. TAF has been studied extensively in randomized clinical trials and real-world studies. TAF-based regimens are recommended over TDF-containing regimens for the improved safety profile.
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Affiliation(s)
- S D Shafran
- Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - G Di Perri
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - S Esser
- Department of Dermatology, University of Duisburg-Essen, Essen, Germany
| | - J-D Lelièvre
- Department of Clinical Immunopathology, Faculté de Médecine de Créteil, Université Paris Est Créteil, Créteil, France
| | - M Parczewski
- Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland
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Hanhoff N, Vu Q, Lang R, Gill MJ. Impact of three decades of antiretroviral therapy in a longitudinal population cohort study. Antivir Ther 2020; 24:153-165. [PMID: 30614788 DOI: 10.3851/imp3287] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND We have used a comprehensive HIV population to characterize antiretroviral therapy (ART), drug class selection, pill burden, drug costs and health outcomes over the entire span of the HIV epidemic. METHODS Antiretroviral (ARV) use (drugs, classes, formulations) and both the laboratory and clinical outcomes (HIV-1 RNA, CD4+ T-cell count and mortality) were determined for all patients in Southern Alberta, Canada, at each year-end between 1986 and 2017. Pill burden, cumulative drug exposure and costs were calculated for each year. RESULTS The number of ARV-treated patients increased from 29.6% (77/260) in 1989 to 93.4% (1,814/1,943) in 2017. Regimen selection showed continuous adjustments for toxicity, resistance, pill burden and adherence. Dramatic improvements in outcomes were seen. In 1997, 22.4% of treated patients had an undetectable viral load, this has been consistently around 90% since 2010 (92.7% in 2017). While HIV-related annual mortality rate declined from 11.0% in 1994 to 0.1% in 2017, all-cause mortality remained relatively stable from 1997 onwards. ART pill burden escalated in 1997 (12.4/day), then decreased to 2.1/day in 2016. Mean ART cost increased in 1997 (CAN$905/month/regimen in 1997, $1,223 in 2016). Mean cumulative lifetime exposure to protease inhibitors is 5.98 ±4.9 and to nucleoside reverse transcriptase inhibitors 8.8 ±6.2 years. CONCLUSIONS Our findings demonstrate not only the immense burden that HIV has imposed on both patients and society, but also the substantial benefit of ART on patient outcomes. They show that research, patient engagement and programme support can with time minimize the harmful long-term effects of HIV-infection.
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Affiliation(s)
- Nikola Hanhoff
- S Alberta HIV Clinic and University of Calgary, Calgary, AB, Canada
| | - Quang Vu
- S Alberta HIV Clinic and University of Calgary, Calgary, AB, Canada
| | - Raynell Lang
- S Alberta HIV Clinic and University of Calgary, Calgary, AB, Canada
| | - M John Gill
- S Alberta HIV Clinic and University of Calgary, Calgary, AB, Canada
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45
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DerSarkissian M, Bhak RH, Oglesby A, Priest J, Gao E, Macheca M, Sharperson C, Duh MS. Retrospective analysis of comorbidities and treatment burden among patients with HIV infection in a US Medicaid population. Curr Med Res Opin 2020; 36:781-788. [PMID: 31944138 DOI: 10.1080/03007995.2020.1716706] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objective: Comorbidities and comedications are important factors influencing optimal therapy because people are living longer with HIV infection. This study describes the long-term comorbidity profile and treatment burden among people with HIV-1 infection.Methods: This retrospective study included Medicaid claims data from patients with ≥1 antiretroviral (ARV) claim between 2016 and 2017 (most recent claim defined the index date), ≥1 HIV diagnosis within 1 year before index, age ≥18 years at first HIV diagnosis and <65 years at index, ≥12 months of continuous eligibility before index, and no history of HIV-2 infection. Comorbidities, concomitant medication use, and pill burden were assessed in the 4 years before index. Analyses were stratified by patient age and treatment experience.Results: Among 3456 patients, the mean (standard deviation [SD]) age was 47.1 (10.4) years; the majority were black (55%) and men (63%). In general, the prevalence of comorbidities increased from the fourth year to the first year before index and included cardiovascular disease (28-40%), hypertension (24-37%), hyperlipidemia (12-17%), and asthma/chronic obstructive pulmonary disease (13-19%). Concomitant medication use corresponding to these comorbidities slightly increased over time. In the year before index, mean (SD) daily pill burden was 2.1 (1.4) for ARVs and 5.9 (5.9) for non-ARVs. Older age and prior treatment experience were associated with higher rates of comorbidities and greater pill burden.Conclusions: In people with HIV infection, comorbidities and concomitant medication use increased with age, supporting considerations for streamlined ARV regimens highlighted in treatment guidelines.
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Affiliation(s)
| | | | - Alan Oglesby
- ViiV Healthcare, Research Triangle Park, NC, USA
| | - Julie Priest
- ViiV Healthcare, Research Triangle Park, NC, USA
| | - Emily Gao
- Analysis Group, Inc., Boston, MA, USA
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Tan DHS, Lee T, Raboud J, Qamar A, Cheung AM, Walmsley S. Alendronate/Vitamin D for attenuating bone mineral density loss during antiretroviral initiation: a pilot randomized controlled trial. HIV Res Clin Pract 2020; 20:140-150. [PMID: 32106792 DOI: 10.1080/25787489.2020.1730114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Background: Antiretroviral therapy (ART) initiation is associated with decreases in bone mineral density (BMD).Objectives: To plan for a larger trial, we sought to obtain preliminary estimates for the difference in the change in BMD at 48 weeks achieved with 24 weeks of prophylactic alendronate/vitamin D during ART initiation compared to no intervention, the within-group standard deviation of this change, and intra-patient correlation coefficient for repeated BMDs. Secondary objectives included assessing enrollment feasibility, treatment acceptability, adherence and safety.Methods: We randomized treatment-naïve HIV-positive adults initiating tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat or abacavir/lamivudine/dolutegravir 1:1:1 to immediate alendronate/vitamin D3 70 mg/5600 IU for 24 weeks (concomitant treatment arm, CTA), the same intervention starting 24 weeks after study entry (delayed treatment arm, DTA), or no bone anti-resorptive therapy (standard of care, SOC). We assessed BMD, acceptability, adverse events and drug adherence at baseline, week 24 and week 48.Results: Of 29 included participants, 72% initiated TDF/FTC/ELV/c and 28% initiated ABC/3TC/DTG. Median (IQR) CD4 count was 388 (303,525) cells/mm3 and median plasma HIV RNA was 4.45 (2.26, 4.84) log10 copies/mL. The mean (SD) percentage change in BMD for the CTA and DTA combined was 1.95% (2.53%), 0.38% (3.34%), and -0.57% (3.50%) at the lumbar spine, femoral neck and total hip respectively at 48 weeks. The ICC among repeated measurements of BMD was 0.978, 0.964, and 0.967 at these sites, respectively. Enrollment feasibility, drug acceptability, adherence, and tolerability were good.Conclusions: Our findings inform the sample size for a larger trial of bone anti-resorptive therapy during ART initiation and support feasibility.
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Affiliation(s)
- Darrell H S Tan
- Division of Infectious Diseases, St. Michael's Hospital, Toronto, Ontario, Canada.,MAP Centre for Urban Health Solutions, St. Michael's Hospital, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Infectious Diseases, Toronto General Hospital, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, Toronto, Ontario, Canada
| | - Terry Lee
- CIHR Canadian HIV Trials Network, Vancouver, British Columbia, Canada
| | - Janet Raboud
- Toronto General Hospital Research Institute, Toronto, Ontario, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Attia Qamar
- MAP Centre for Urban Health Solutions, St. Michael's Hospital, Toronto, Ontario, Canada
| | - Angela M Cheung
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, Toronto, Ontario, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Centre for Excellence in Skeletal Health Assessment, Toronto General Hospital, Toronto, Ontario, Canada
| | - Sharon Walmsley
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Infectious Diseases, Toronto General Hospital, Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, Toronto, Ontario, Canada
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Fractures Related to Tenofovir: A Case/Noncase Study in the European Pharmacovigilance Database. Am J Ther 2020; 26:e589-e592. [PMID: 29324463 DOI: 10.1097/mjt.0000000000000718] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND There is no clear consensus on the relationship between tenofovir (TDF) and fracture risk because the studies published so far present contradictory findings. STUDY QUESTION Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of fracture risk during TDF exposure in patients infected with HIV. METHODS Herein, we analyze all the cases of fractures suspected to be related to TDF recorded in EudraVigilance between 2001 and November 10, 2016. A case/noncase method was used to assess the association between fractures and TDF, calculating proportional reporting ratios (PRRs) and their 95% confidence intervals (CIs) as a measure of disproportionality. According to the Medical Dictionary for Regulatory Activities (MedDRA) terminology, osteoporotic fractures are included in High Level Group Term (HLGT) "Fractures" and traumatic fractures in HLGT "Bone and joint injuries," so, we selected cases included in both HLGTs. The noncases used as controls were all the remaining adverse drug reaction reports recorded in EudraVigilance during the same period. RESULTS There were 68,113 cases of fractures in the 4,776,472 reports recorded in EudraVigilance during the study period. TDF was involved in 181 cases. The median latency period until the appearance of fracture was 995 days. TDF was present as the only suspect drug in 140 cases. The PRR of TDF and fractures was 1.11 (95% CI, 0.96-1.28). Nevertheless, disproportionality was observed for some types of fractures: osteoporotic fractures (PRR 17.24; 95% CI, 9.90-30.01), bone fissure (PRR 16.60; 95% CI, 6.11-45.10), and pathological fracture (PRR 4.40; 95% CI, 2.77-7.00). CONCLUSIONS Our findings do not show a disproportionality for fractures in patients treated with TDF, although disproportionality was found for some types of fractures, mainly osteoporotic fractures.
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Havens PL, Perumean-Chaney SE, Patki A, Cofield SS, Wilson CM, Liu N, Anderson PL, Landovitz RJ, Kapogiannis BG, Hosek SG, Mulligan K. Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113. Clin Infect Dis 2020; 70:687-691. [PMID: 31179503 PMCID: PMC7319267 DOI: 10.1093/cid/ciz486] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 06/06/2019] [Indexed: 01/13/2023] Open
Abstract
Human immunodeficiency virus-seronegative men aged 15-22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15-19 years. Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).
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Affiliation(s)
- Peter L Havens
- Department of Pediatrics, Medical College of Wisconsin/Children’s Hospital of Wisconsin, Milwaukee
| | | | - Amit Patki
- Department of Biostatistics, University of Alabama at Birmingham
| | - Stacey S Cofield
- Department of Biostatistics, University of Alabama at Birmingham
| | - Craig M Wilson
- Department of Epidemiology, University of Alabama at Birmingham
| | | | - Peter L Anderson
- Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora
| | - Raphael J Landovitz
- Department of Medicine, David Geffen School of Medicine, University of California Los Angeles
| | - Bill G Kapogiannis
- Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
| | - Sybil G Hosek
- Department of Psychiatry, Stroger Hospital of Cook County, Chicago, Illinois
| | - Kathleen Mulligan
- Department of Medicine, University of California at San Francisco, Zuckerberg San Francisco General Hospital
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Tao X, Lu Y, Zhou Y, Zhang L, Chen Y. Efficacy and safety of the regimens containing tenofovir alafenamide versus tenofovir disoproxil fumarate in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection: A meta-analysis of randomized controlled trials. Int J Infect Dis 2020; 93:108-117. [PMID: 31988012 DOI: 10.1016/j.ijid.2020.01.035] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 01/15/2020] [Accepted: 01/20/2020] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) can cause renal and bone toxicity, which is associated with high plasma tenofovir concentrations in antiretroviral treatment of HIV-1 infected patients. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. We aimed to assess the non-inferiority of a TAF-containing combination regimen versus a TDF-containing fixed-dose single-tablet regimen in the antiretroviral-treatment-naive, HIV-1-infected patients. METHODS We searched PubMed, Embase, Web of Science, and the Cochrane Trial Registry, from January 2001 to July 2019, using relevant keywords. Available data were extracted from eligible randomized trials (RCTs) and pooled as risk ratios (RRs) or standardized mean differences (SMDs) in a meta-analysis model using Stata/SE. RESULTS We included seven eligible randomized controlled trials (RCTs) with a total of 6269 participants. Patients who were antiretroviral-naive adults with HIV-1 on both the TAF-containing regimens and the TDF-containing regimens had similar virologic suppression effects (RR, 1.02; 95% CI, 1.00-1.04; p > 0.05) at week 24 (93.99% vs. 94.20%), week 48 (90.71% vs. 89.54%), and week 96 (86.16% vs. 84.80%). Both groups had no significant improvements in CD4 cell count for the naive patients during 48 weeks of therapy (SMD, 0.09; 95% CI, 0.01 to 0.16; p < 0.05). Both treatments were safe and well-tolerated, and most adverse events were similar as mild to moderate in severity. Moreover, compared with the TDF-containing regimens, the TAF-containing regimens in patients had significantly smaller reductions in both hip (RR, 0.33; 95CI, 0.29-0.39; p < 0.05) and spine (RR, 0.58; 95CI, 0.51-0.65; p < 0.05). Additionally, the TAF-containing regimens in patients had significantly fewer increases for renal events than those of the TDF-containing regimens through 48 weeks (0.31; 95% CI, 0.18-0.55; p < 0.05). CONCLUSIONS Our meta-analysis indicated that efficacy, safety, and tolerability of TAF-containing regimens were non-inferior in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection. Furthermore, compared with those receiving the TDF-containing regimens, patients on the TAF-containing regimens had significant advantages in renal function, bone parameters, and lipid profile for the naive patients.
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Affiliation(s)
- Xingbao Tao
- National Key Laboratory for Infectious Diseases Prevention and Treatment with Traditional Chinese Medicine, Chongqing Public Health Medical Center, Chongqing, 400036, China; Department of Infection Diseases, Chongqing Public Health Medical Center, Chongqing, 400036, China
| | - Yanqiu Lu
- Department of Infection Diseases, Chongqing Public Health Medical Center, Chongqing, 400036, China
| | - Yihong Zhou
- Department of Infection Diseases, Chongqing Public Health Medical Center, Chongqing, 400036, China
| | - Lvlang Zhang
- Department of Infection Diseases, Chongqing Public Health Medical Center, Chongqing, 400036, China
| | - Yaokai Chen
- National Key Laboratory for Infectious Diseases Prevention and Treatment with Traditional Chinese Medicine, Chongqing Public Health Medical Center, Chongqing, 400036, China; Department of Infection Diseases, Chongqing Public Health Medical Center, Chongqing, 400036, China.
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Chokuda E, Reynolds C, Das S. Association of Low Vitamin D with Complications of HIV and AIDS: A literature Review. Infect Disord Drug Targets 2020; 20:122-142. [PMID: 30574856 DOI: 10.2174/1871526519666181221122731] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/13/2018] [Accepted: 12/14/2018] [Indexed: 06/09/2023]
Abstract
With the advent of combination antiretroviral therapy (cART), the survival of HIV patients has improved dramatically, but the complications of the disease and treatment have become an important issue in the management of HIV patients. Vitamin-D deficiency is common in HIV patients. Low vitamin-D is associated with different comorbidities in the HIV uninfected general population. In this review, we first briefly describe vitamin D synthesis and mechanism of action and we focus on the epidemiological and clinical data dealing with the relationship between vitamin D deficiency in HIV infection with several comorbidities which has been found to be increasingly common in patients living with HIV infection. We searched the PubMed database using the keywords "HIV," "vitamin D" and other common disorders or conditions that are relatively common in HIV infection. The other conditions included in the search were osteoporosis and fracture, cardiovascular disease, diabetes and insulin resistance, active tuberculosis, hepatitis-C co-infection, and HIV disease progression. Articles presenting original data as well as systematic reviews and met analysis related to HIV population were included in our analysis. Vitamin-D deficiency seems to be associated with several adverse outcomes in HIV patients but a definite cause and effect relationship with vitamin-D is yet to be confirmed in most of the cases. However, the literature supporting the efficacy of vitamin-D supplementation is lacking.
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Affiliation(s)
- Evelyn Chokuda
- Department of HIV Medicine, Coventry & Warwickshire Partnership Trust, Coventry, United Kingdom
| | - Chris Reynolds
- Department of HIV Medicine, Coventry & Warwickshire Partnership Trust, Coventry, United Kingdom
| | - Satyajit Das
- Department of HIV Medicine, Coventry & Warwickshire Partnership Trust, Coventry, United Kingdom
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