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1
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Joshi M, Clark B, Lee TA. Fanconi Syndrome in Patients With Human Immunodeficiency Virus Treated With Tenofovir-Based Antiretroviral Therapy: A Systematic Literature Review. Ann Pharmacother 2024; 58:857-869. [PMID: 37932920 DOI: 10.1177/10600280231206703] [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] [Indexed: 11/08/2023] Open
Abstract
OBJECTIVE Several cases of Fanconi syndrome (FS), a severe form of nephrotoxicity, have been reported in patients with HIV on tenofovir-containing antiretroviral therapy. A systematic review of the published literature on tenofovir-related FS in patients with HIV was conducted. DATA SOURCES PubMed and Embase were queried to identify articles in English published between January 2005 and June 2023, reporting tenofovir-related FS in adults with HIV. Preclinical studies, conference/poster abstracts, commentaries and responses, and review papers were excluded. STUDY SELECTION AND DATA EXTRACTION Of the 256 articles screened, 57 met the inclusion criteria. These comprised 37 case reports, 11 case series, 1 cross-sectional study, 1 case-control study, 4 cohort studies, 1 single-arm open-label clinical trial, 1 sub-analysis of clinical trials, and 1 pooled analysis of clinical trials. DATA SYNTHESIS Among 56 cases on which information was abstracted, median age at FS diagnosis was 50 years, 51.8% were men, and duration of tenofovir use ranged from 6 weeks to 11 years. Ritonavir was co-prescribed in almost half the cases. In observational and interventional studies, incidence of FS was low. Many studies reported resolution of FS symptoms after tenofovir discontinuation. All FS occurrences were identified in those on tenofovir disoproxil fumarate (TDF), except for one patient on tenofovir alafenamide (TAF). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE Continuous monitoring of signs and symptoms of renal and bone toxicity is essential for patients with HIV on tenofovir-containing therapy. CONCLUSIONS Occurrence of FS is low in patients with HIV treated with tenofovir-based regimens. Concomitant use of ritonavir may increase risk of FS. TAF may be a safer alternative than TDF in terms of nephrotoxicity.
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Affiliation(s)
- Mrinmayee Joshi
- College of Pharmacy, University of Illinois Chicago, Chicago, IL, USA
| | - Brendan Clark
- College of Pharmacy, University of Illinois Chicago, Chicago, IL, USA
| | - Todd A Lee
- College of Pharmacy, University of Illinois Chicago, Chicago, IL, USA
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2
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Odhiambo F, Nareeba S, Mwangeka G, Njambi A, Nyakebati V. Tenofovir induced Fanconi syndrome in a middle age African female from Kenya, East Africa: Case report and brief literature review. Clin Case Rep 2024; 12:e8889. [PMID: 38799537 PMCID: PMC11126650 DOI: 10.1002/ccr3.8889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 04/15/2024] [Accepted: 04/19/2024] [Indexed: 05/29/2024] Open
Abstract
This case presentation highlights the need to routinely monitor renal function in patients on Tenofovir Disoproxil Fumarate (TDF) due to its side effect of proximal tubule dysfunction. Abstract This is a case presentation of a 50-year-old African female who had been on a Tenofovir based regimen for 12 years and developed Fanconi syndrome. She recovered after discontinuation of the Tenofovir Disoproxil Fumarate (TDF).
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3
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Choy CY, Wong CS, Kumar PA, Olszyna DP, Teh YE, Chien MFJ, Kurup A, Koh YL, Ho LP, Law HL, Chua NGS, Yong HYJ, Archuleta S. Recommendations for the use of antiretroviral therapy in adults living with human immunodeficiency virus in Singapore. Singapore Med J 2024; 65:259-273. [PMID: 35366662 PMCID: PMC11182460 DOI: 10.11622/smedj.2021174] [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: 10/20/2020] [Accepted: 07/06/2021] [Indexed: 11/18/2022]
Abstract
ABSTRACT Since the advent of combination antiretroviral therapy (ART), the mortality attributable to human immunodeficiency virus (HIV) infection has decreased by 80%. Newer antiretroviral agents are highly efficacious, have minimal side effects as compared to older drugs, and can be formulated as combination tablets to reduce patients' pill burden. Despite these advances, 680,000 people worldwide died of acquired immunodeficiency syndrome-related illnesses in 2020. The National ART and Monitoring Recommendations by the National HIV Programme have been created to guide physicians on the prescribing of ART based on the patients' needs. These recommendations are based on international guidelines and tailored to the local context and unique domestic considerations. We hoped that with the publication of these recommendations, the care of people living with HIV can be enhanced, bringing us closer to ending HIV in our lifetime.
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Affiliation(s)
- Chiaw Yee Choy
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore
- National Centre for Infectious Diseases, Singapore
| | - Chen Seong Wong
- Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore
- National Centre for Infectious Diseases, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - P Arun Kumar
- National Centre for Infectious Diseases, Singapore
| | - Dariusz Piotr Olszyna
- Division of Infectious Diseases, University Medicine Cluster, National University Hospital, Singapore
| | - Yii Ean Teh
- Department of Infectious Diseases, Singapore General Hospital, Singapore
| | | | - Asok Kurup
- Infectious Diseases Care Pte Ltd, Mount Elizabeth Medical Centre, Singapore
| | - Yin Ling Koh
- The Novena Medical Specialists, Mount Elizabeth Novena Specialist Centre, Singapore
| | - Lai Peng Ho
- Department of Care and Counselling, Tan Tock Seng Hospital, Singapore
| | - Hwa Lin Law
- Department of Pharmacy, Tan Tock Seng Hospital, Singapore
| | | | | | - Sophia Archuleta
- National Centre for Infectious Diseases, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Infectious Diseases, University Medicine Cluster, National University Hospital, Singapore
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4
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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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Kichloo A, Chugh SS, Gupta S, Panday J, Goldar GE. Tenofovir and Severe Symptomatic Hypophosphatemia. J Investig Med High Impact Case Rep 2020; 7:2324709619848796. [PMID: 31142127 PMCID: PMC6545665 DOI: 10.1177/2324709619848796] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Tenofovir is a broadly used drug used for the treatment of human immunodeficiency virus (HIV). Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria. It is both filtered in the glomerulus and actively secreted in the tubules for elimination and is excreted unchanged in the urine. Studies have shown an active transportation of 20-30% of this drug into the renal proximal tubule (PCT) cells via the organic anion transporters in the baso-lateral membrane (primarily hOAT1, and OAT3 to a lesser extent) and ultimate excretion of the drug into the tubular lumen via the transporters in the proximal tubular apical membrane MRP4 and MRP2 (multidrug resistance-associated proteins 2 & 4). Subsequently, the mitochondrial injury caused by Tenofovir can lead to the development of Fanconi's syndrome which causes renal tubular acidosis, phosphaturia, aminoaciduria, glucosuria with normoglycemia, and tubular proteinuria. Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.
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Affiliation(s)
- Asim Kichloo
- 1 St. Mary's Hospital, Saginaw, MI, USA.,2 Central Michigan University, Mount Pleasant, MI, USA
| | - Savneek Singh Chugh
- 3 Westchester Medical Center, Valhalla, NY, USA.,4 Newyork Medical College, Valhalla, NY, USA
| | - Sanjeev Gupta
- 3 Westchester Medical Center, Valhalla, NY, USA.,4 Newyork Medical College, Valhalla, NY, USA
| | - Jay Panday
- 3 Westchester Medical Center, Valhalla, NY, USA.,4 Newyork Medical College, Valhalla, NY, USA
| | - Ghazaleh Emedis Goldar
- 1 St. Mary's Hospital, Saginaw, MI, USA.,2 Central Michigan University, Mount Pleasant, MI, USA
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Zaid D, Greenman Y. Human Immunodeficiency Virus Infection and the Endocrine System. Endocrinol Metab (Seoul) 2019; 34:95-105. [PMID: 31257738 PMCID: PMC6599897 DOI: 10.3803/enm.2019.34.2.95] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 04/24/2019] [Accepted: 05/13/2019] [Indexed: 12/29/2022] Open
Abstract
In the current era of effective antiretroviral therapies (ARTs), human immunodeficiency virus (HIV) infection became a chronic disorder that requires long term follow-up. Among other medical issues, these patients may develop endocrine problems, specific to HIV infection and its treatment. The purpose of this review is to give an overview of common endocrine complications associated with HIV infection, and to propose diagnostic and therapeutic strategies. HIV can affect the endocrine system at several levels. Adrenal and gonadal dysfunction, osteoporosis with increased fracture risk, dyslipidemia with increased cardiovascular risk, are some of the endocrine disorders prevalent in HIV-infected patients that may negatively influence quality of life, and increase morbidity and mortality. While ARTs have dramatically increased life expectancy in the HIV-infected population, they are not devoid of adverse effects, including endocrine dysfunction. Physicians caring for HIV-infected patients should be knowledgeable and exercise a high index of suspicion for the diagnosis of endocrine abnormalities, and in particular be aware of those that can be life threatening. Endocrine evaluation should follow the same strategies as in the general population, including prevention, early detection, and treatment.
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Affiliation(s)
- Dana Zaid
- Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel
| | - Yona Greenman
- Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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7
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Sury K, Perazella MA. The Changing Face of Human Immunodeficiency Virus-Mediated Kidney Disease. Adv Chronic Kidney Dis 2019; 26:185-197. [PMID: 31202391 DOI: 10.1053/j.ackd.2018.12.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 12/03/2018] [Accepted: 12/06/2018] [Indexed: 01/09/2023]
Abstract
In nearly 40 years since human immunodeficiency virus (HIV) first emerged, much has changed. Our understanding of the pathogenesis of HIV infection and its effect on the cells within each kidney compartment has progressed, and the natural history of the disease has been transformed. What was once an acutely fatal illness is now a chronic disease managed with oral medications. This change is largely due to the advent of antiretroviral drugs, which have dramatically altered the prognosis and progression of HIV infection. However, the success of antiretroviral therapy has brought with it new challenges for the nephrologist caring for patients with HIV/acquired immune deficiency syndrome, including antiretroviral therapy-induced nephrotoxicity, development of non-HIV chronic kidney disease, and rising incidence of immune-mediated kidney injury. In this review, we discuss the pathogenesis of HIV infection and how it causes pathologic changes in the kidney, review the nephrotoxic effects of select antiretroviral medications, and touch upon other causes of kidney injury in HIV cases, including mechanisms of acute kidney injury, HIV-related immune complex glomerular disease, and thrombotic microangiopathy.
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8
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Lee JE, Lee S, Song SH, Kwak IS, Lee SH. Incidence and risk factors for tenofovir-associated nephrotoxicity among human immunodeficiency virus-infected patients in Korea. Korean J Intern Med 2019; 34:409-417. [PMID: 29020764 PMCID: PMC6406099 DOI: 10.3904/kjim.2016.418] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 04/09/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND/AIMS Little is known about tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in Korea. The objective of this study was to evaluate the incidence and risk factors of TDF-associated nephrotoxicity among HIV-infected patients in Korea. METHODS A single-center retrospective cohort study was conducted on HIVinfected patients in Korea. We included patients who had started TDF or abacavir (ABC)-based antiretroviral therapy (ART) between October 2006 and December 2014. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease-Epidemiology Collaboration equation. Renal dysfunction was defined as > 25% decrease of baseline eGFR. A propensity matched case-control study was conducted to compare renal dysfunction rates between the two groups. The risk factors of nephrotoxicity were analyzed by Cox regression analysis. RESULTS A total of 210 HIV-infected patients were included in the study, of which, 108 were TDF-based ART group and 102 were ABC-based ART group. Renal dysfunction occurred in 16 patients (14.8%) in the TDF group and 11 (10.8%) in the ABC group. Incidence of renal dysfunction of TDF and ABC group was 9.66 per 100 person-years (PYs) and 5.14 per 100 PYs, respectively (p = 0.176). In propensityscore-matched analysis, renal dysfunction rates were TDF 13.3% versus ABC 13.3% (p > 0.999). In multivariable analysis, Centers for Disease Control and Prevention clinical category C was a significant risk factor for renal dysfunction. CONCLUSION Approximately, 13% of HIV-infected patients treated with TDF had renal dysfunction. Advanced stage of HIV infection was a significant risk factor for renal dysfunction.
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Affiliation(s)
- Jeong Eun Lee
- Division of Infectious Disease, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Shinwon Lee
- Division of Infectious Disease, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Sang Heon Song
- Division of Nephrology, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Ihm Soo Kwak
- Division of Nephrology, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Sun Hee Lee
- Division of Infectious Disease, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
- Correspondence to Sun Hee Lee, M.D. Division of Infectious Diseases, Department of Internal Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea Tel: +82-51-240-7673 Fax: +82-51-247-3213 E-mail:
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9
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Sajith KG, Kapoor N, Shetty S, Goel A, Zachariah U, Eapen CE, Paul TV. Bone Health and Impact of Tenofovir Treatment in Men with Hepatitis-B Related Chronic Liver Disease. J Clin Exp Hepatol 2018; 8:23-27. [PMID: 29743793 PMCID: PMC5938523 DOI: 10.1016/j.jceh.2017.05.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 05/02/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Chronic Liver Disease (CLD) has been shown to have an adverse impact on bone health. Hepatitis-B related CLD and its treatment with tenofovir may have additional effects on skeleton. OBJECTIVE To study the impact of HBV related CLD and its treatment with Tenofovir on bone health in Indian subjects. METHODS This cross sectional study included men (18-60 years) and comprised of three groups: Group-1 was treatment naïve HBV related CLD (n = 79), Group-2 those with HBV related CLD on tenofovir for at least 1 year (n = 136), Group-3 age, sex and Body Mass Index (BMI) matched healthy controls (n = 58). Bone biochemistry and Bone Mineral Density (BMD) at spine, Femoral Neck (FN) and forearm were studied. Independent t-test or ANOVA was used to compare the means of continuous variables and chi-square test for categorical variables. Multiple logistic regression was used to assess the factors causing Low Bone Mass (LBM) at FN. RESULTS A significantly greater proportion (P < 0.05) of patients (40%) with CLD (group 1 and group 2) had vitamin D deficiency (<20 ng/ml) in comparison with control group (22%). The mean serum C-Terminal telopeptide was significantly higher (P < 0.05) and the mean BMD was significantly lower (P < 0.05) in subjects with HBV related CLD than controls. The prevalence of LBM was higher in group 1 at the spine (31%) and forearm (18.4%) when compared to controls (8.1% and 7.8% respectively) (P < 0.05). The proportion of patients with LBM at FN was highest in group 2 (12.3%) compared to those in group 1 (8%) and group 3 (4%) (P < 0.05). Advanced age, low BMI, and high viral load (>10,000 IU/ml) emerged as significant risk factors for LBM at FN. CONCLUSION The impact of hepatitis-B related CLD as well as its treatment on bone health is significant. Bone health need to be periodically evaluated in these subjects especially in older men who are lean and have a higher viral load.
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Affiliation(s)
- Kattiparambil G. Sajith
- Professor, Department of Hepatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Nitin Kapoor
- Associate Professor, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Sahana Shetty
- Assistant Professor, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Ashish Goel
- Professor, Department of Hepatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Uday Zachariah
- Professor, Department of Hepatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
| | - Chundamannil E. Eapen
- Professor & Head, Department of Hepatology, Christian Medical College and Hospital, Tamil Nadu, India
| | - Thomas V. Paul
- Professor, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
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Kim D, Lee J, Kim DH, Kang K, Suh SJ, Jung YK, Yim HJ. [A Case of Tenofovir-associated Fanconi Syndrome in Patient with Chronic Hepatitis B]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 68:317-320. [PMID: 28025475 DOI: 10.4166/kjg.2016.68.6.317] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Tenofovir disoproxil fumarate (TDF) is one of the most widely used treatment options for human immunodeficiency virus (HIV) and HBV infections. Despite its efficacy and safety, some cases of nephrotoxicity have been reported in the treatment of HIV patients. Even more recently, very few cases of Fanconi syndrome associated with tenofovir therapy in HBV monoinfection have been reported. Herein, we report a case of a 47-year-old male with an HBV monoinfection, who developed Fanconi syndrome and a secondary osteomalacia with multiple bone pain. After TDF withdrawal and supplementation of calcitriol, his renal function was reverted. Although the overall risk of TDF-associated nephrotoxicity is very low, both glomerular and tubular function should be monitored in patients undergoing TDF treatment.
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Affiliation(s)
- Dongwoo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jongjin Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Dae Ha Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kyuho Kang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang Jun Suh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Bilateral Hip Fracture in Adolescents With Antiretroviral Treatment. JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS GLOBAL RESEARCH AND REVIEWS 2017; 1:e005. [PMID: 30211347 PMCID: PMC6132306 DOI: 10.5435/jaaosglobal-d-17-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Tenofovir is a nucleotide reverse transcriptase inhibitor, a commonly prescribed antiretroviral as part of initial therapy. It is widely used and has been recognized as a cause of acquired Fanconi syndrome, a disorder characterized by renal tubular dysfunction, which leads to hypophosphatemia, hypokalemia, and metabolic acidosis, as well as symptoms of polyuria and dehydration, which can ultimately lead to defects in bone mineralization and increase risk of fracture.
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12
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Kayaaslan B, Guner R. Adverse effects of oral antiviral therapy in chronic hepatitis B. World J Hepatol 2017; 9:227-241. [PMID: 28261380 PMCID: PMC5316843 DOI: 10.4254/wjh.v9.i5.227] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 11/22/2016] [Accepted: 12/09/2016] [Indexed: 02/06/2023] Open
Abstract
Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a “Black Box” warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment.
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Sudjaritruk T, Bunupuradah T, Aurpibul L, Kosalaraksa P, Kurniati N, Sophonphan J, Ananworanich J, Puthanakit T. Impact of tenofovir disoproxil fumarate on bone metabolism and bone mass among perinatally HIV-infected Asian adolescents. Antivir Ther 2016; 22:471-479. [PMID: 27786155 DOI: 10.3851/imp3103] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2016] [Indexed: 10/20/2022]
Abstract
BACKGROUND This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents. METHODS This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated. RESULTS Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated. CONCLUSIONS Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.
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Affiliation(s)
- Tavitiya Sudjaritruk
- Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
| | | | - Linda Aurpibul
- Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Pope Kosalaraksa
- Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Nia Kurniati
- Department of Child Health, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | | | - Jintanat Ananworanich
- HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.,Present address: The Henry M Jackson Foundation for the Advancement of Military Medicine, the US Military HIV Research Program, Bethesda, MD, USA
| | - Thanyawee Puthanakit
- HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.,Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,Research Unit in Pediatric Infectious Diseases and Vaccine, Chulalongkorn University, Bangkok, Thailand
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A Review of Management of Inflammation in the HIV Population. BIOMED RESEARCH INTERNATIONAL 2016; 2016:3420638. [PMID: 27766258 PMCID: PMC5059528 DOI: 10.1155/2016/3420638] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 08/12/2016] [Accepted: 08/25/2016] [Indexed: 12/14/2022]
Abstract
Advancements in antiretroviral therapy have drastically increased the life expectancy for those infected with HIV. Today, a new subgroup of older patients with long-term controlled HIV exists, and its populace is continuously mounting. Therefore, it is essential to understand the enduring effects of chronic suppressed HIV infection in order to further improve HIV management in these patients. This paper will examine the role of HIV in chronic inflammation and immune dysfunction, the dynamic interaction that exists between comorbidity and HIV, and the potential consequences of long-term antiretroviral therapy in an effort to provide the best management options for the virally suppressed HIV patient.
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Bone Mineral Density Changes Among Young, Healthy African Women Receiving Oral Tenofovir for HIV Preexposure Prophylaxis. J Acquir Immune Defic Syndr 2016; 71:287-94. [PMID: 26866954 PMCID: PMC4755358 DOI: 10.1097/qai.0000000000000858] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Limited data exist on effect of tenofovir disoproxil fumarate (TDF) when used for preexposure prophylaxis (PrEP) on bone mineral density (BMD) in HIV-negative women. We evaluated the effect of daily oral TDF and emtricitabine/TDF compared with placebo on BMD among women enrolled in an HIV-1 PrEP trial. METHODS HIV-uninfected women in Uganda and Zimbabwe had BMD measurements of lumbar spine (LS) and total hip (TH) by dual-energy x-ray absorptiometry at baseline and every 24 weeks for 48 weeks of active treatment and for 48 weeks after discontinuation of study medication. Plasma tenofovir levels were assessed every 12 weeks for the first 48 weeks. RESULTS Of 518 women enrolled, 432 had dual-energy x-ray absorptiometry results at baseline and week 48. In the primary analysis, no significant differences in percent BMD change in hip or spine between arms observed, likely because of low product adherence. Among the subset with tenofovir detection in 75%-100% of plasma samples, the mean percent BMD change from baseline to week 48 in the LS was 1.4% lower for TDF or emtricitabine/TDF recipients than for placebo (P = 0.002) and TH BMD was 0.9% lower (P = 0.018). BMD changes from end of active treatment to 48 weeks were significantly greater in the active arm participants compared with placebo participants with a net difference of approximately +0.9% at the LS (P = 0.007) and +0.7% (P = 0.003) at the TH. CONCLUSIONS TDF-containing oral PrEP resulted in small but significant reversible decreases in hip and spine BMD among young African women.
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Matovu FK, Wattanachanya L, Beksinska M, Pettifor JM, Ruxrungtham K. Bone health and HIV in resource-limited settings: a scoping review. Curr Opin HIV AIDS 2016; 11:306-25. [PMID: 27023284 PMCID: PMC5578733 DOI: 10.1097/coh.0000000000000274] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Sub-Saharan Africa and other resource-limited settings (RLS) bear the greatest burden of the HIV epidemic globally. Advantageously, the expanding access to antiretroviral therapy (ART) has resulted in increased survival of HIV individuals in the last 2 decades. Data from resource rich settings provide evidence of increased risk of comorbid conditions such as osteoporosis and fragility fractures among HIV-infected populations. We provide the first review of published and presented data synthesizing the current state of knowledge on bone health and HIV in RLS. RECENT FINDINGS With few exceptions, we found a high prevalence of low bone mineral density (BMD) and hypovitaminosis D among HIV-infected populations in both RLS and resource rich settings. Although most recognized risk factors for bone loss are similar across settings, in certain RLS there is a high prevalence of both non-HIV-specific risk factors and HIV-specific risk factors, including advanced HIV disease and widespread use of ART, including tenofovir disoproxil fumarate, a non-BMD sparing ART. Of great concern, we neither found published data on the effect of tenofovir disoproxil fumarate initiation on BMD, nor any data on incidence and prevalence of fractures among HIV-infected populations in RLS. SUMMARY To date, the prevalence and squeal of metabolic bone diseases in RLS are poorly described. This review highlights important gaps in our knowledge about HIV-associated bone health comorbidities in RLS. This creates an urgent need for targeted research that can inform HIV care and management guidelines in RLS.
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Affiliation(s)
- Flavia Kiweewa Matovu
- Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration
- Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda
- School of Public Health, University of the Witwatersrand, Johannesburg, South Africa
- Flavia Kiweewa Matovu and Lalita Wattanachanya contributed equally to the writing of this article
| | - Lalita Wattanachanya
- Division of Endocrinology and Metabolism, Department of Medicine, and Hormonal and Metabolic Disorders Research Unit, Faculty of Medicine, Chulalongkorn University
- Excellence Center for Diabetes, Hormone, and Metabolism, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Flavia Kiweewa Matovu and Lalita Wattanachanya contributed equally to the writing of this article
| | - Mags Beksinska
- Maternal, Adolescent and Child Health (MatCH) Research, University of the Witwatersrand, Faculty of Health Sciences, Department of Obstetrics and Gynaecology
| | - John M. Pettifor
- School of Public Health, University of the Witwatersrand, Johannesburg, South Africa
- MRC/Wits Developmental Pathways for Health Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Kiat Ruxrungtham
- Department of Medicine, Faculty of Medicine, Chulalongkorn University
- HIV-NAT, Thai Red Cross AIDS Research Center, Thai Red Cross Society, Bangkok, Thailand
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Abstract
Tenofovir is currently the only commercially available nucleotidic reverse-transcriptase inhibitor of human immunodeficiency virus (HIV). It is overall very well tolerated and is prescribed to millions of patients-without any specific monitoring in developing countries. However a significant nephrotoxicity has been described. Acute nephrotoxicity is well characterized. Tenofovir is excreted in urine by proximal tubular epithelial cells. In case of cytoplasmic accumulation, tenofovir inhibits mitochondrial DNA polymerase γ, which causes a dysfunction of the respiratory chain, and in turn an alteration of the energy-deprived cells. Fanconi syndrome is the clinical expression of tenofovir acute toxicity, with sometimes an associated acute kidney failure. These abnormalities are usually reversible, at least partially, when tenofovir is discontinued. Tenofovir chronic toxicity has been debated but seems now well established by several cohort studies, even though it pathophysiology has yet to be understood. It manifests as an accelerated glomerular filtration rate decline in treated patients with no other renal abnormalities. The identification of this chronic toxicity was probably blurred by multiple cofactors, usually excluded from clinical trials. Simple measures such as dose adaptation to kidney function, identification of risk factors, and plasmatic tenofovir concentration monitoring can help decrease the risk of nephrotoxicity.
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Affiliation(s)
- Corinne Isnard-Bagnis
- Service d'urologie néphrologie transplantation, groupe hospitalier universitaire Pitié-Salpêtrière-Charles-Foix, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; Université Pierre-et-Marie-Curie, 4, place Jussieu, 75005 Paris, France
| | - Blandine Aloy
- Service d'urologie néphrologie transplantation, groupe hospitalier universitaire Pitié-Salpêtrière-Charles-Foix, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; Service information conseil adaptation rénale (Icar), groupe hospitalier universitaire Pitié-Salpêtrière-Charles-Foix, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France
| | - Gilbert Deray
- Service d'urologie néphrologie transplantation, groupe hospitalier universitaire Pitié-Salpêtrière-Charles-Foix, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; Université Pierre-et-Marie-Curie, 4, place Jussieu, 75005 Paris, France; Service information conseil adaptation rénale (Icar), groupe hospitalier universitaire Pitié-Salpêtrière-Charles-Foix, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France
| | - Jérôme Tourret
- Service d'urologie néphrologie transplantation, groupe hospitalier universitaire Pitié-Salpêtrière-Charles-Foix, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; Université Pierre-et-Marie-Curie, 4, place Jussieu, 75005 Paris, France.
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Mugwanya KK, Baeten JM. Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention. Expert Opin Drug Saf 2015; 15:265-73. [PMID: 26634852 DOI: 10.1517/14740338.2016.1128412] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. AREAS COVERED We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. EXPERT OPINION TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP's substantial reduction in the risk of HIV infection.
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Affiliation(s)
- Kenneth K Mugwanya
- a Department of Epidemiology , University of Washington , Seattle , WA , USA.,b Department of Global Health , University of Washington , Seattle , WA , USA.,c Division of Disease Control, School of Public Health , Makerere University , Kampala , Uganda
| | - Jared M Baeten
- a Department of Epidemiology , University of Washington , Seattle , WA , USA.,b Department of Global Health , University of Washington , Seattle , WA , USA.,d Department of Medicine , University of Washington , Seattle , WA , USA
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Abstract
The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date.
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Affiliation(s)
- Alice K Pau
- Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11C103 (MSC 1880), Bethesda, MD 20892, USA.
| | - Jomy M George
- Department of Pharmacy Practice and Administration, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, GH-108K, Philadelphia, PA 19104, USA
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Tien C, Xu JJ, Chan LS, Chang M, Lim C, Lee S, Huh B, Shinada S, Bae HS, Fong TL. Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling. Dig Dis Sci 2015; 60:566-72. [PMID: 25239496 DOI: 10.1007/s10620-014-3363-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Accepted: 09/08/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Increased risk of defective urinary phosphate reabsorption and osteoporosis has been reported in HIV and chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF). AIMS Goals of this study were to evaluate the prevalence of renal phosphate wasting and abnormal bone mineral density in CHB patients taking TDF compared to CHB patients treated with entecavir (ETV) and untreated CHB patients. METHODS This is a cross-sectional study of 146 consecutive Asian-American CHB patients who were treatment naïve (n = 60) or treated with either TDF (n = 42) or ETV (n = 44). Proximal tubular handling of phosphate was assessed by the maximal rate of tubular reabsorption of phosphate (TmPO4) divided by glomerular filtration rate (GFR) (TmPO4/GFR). Bone mineral density (BMD) was measured using dual X-ray absorptiometry. RESULTS TmPO4/GFR was similar among CHB patients treated with TDF compared to untreated patients and patients taking ETV. However, among patients treated with ≥18 months of TDF or ETV, prevalence of abnormal TmPO4/GFR was higher among patients treated with TDF compared to ETV (48.5 % (16/33) vs. 12.5 % (3/24), p = 0.005). Overall prevalence of osteoporosis in this cohort of CHB patients was 14 %, with no significant difference between the three groups. Renal phosphate handling did not correlate with osteoporosis. CONCLUSIONS Chronic hepatitis B patients treated with ≥18 months of TDF experienced an increased risk of proximal tubular dysfunction. TDF did not increase the risk of osteoporosis. Longitudinal studies are needed to confirm these findings.
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Affiliation(s)
- Connie Tien
- Asian Pacific Liver Center, Saint Vincent Medical Center, Los Angeles, CA, USA
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Gill US, Zissimopoulos A, Al-Shamma S, Burke K, McPhail MJW, Barr DA, Kallis YN, Marley RTC, Kooner P, Foster GR, Kennedy PTF. Assessment of bone mineral density in tenofovir-treated patients with chronic hepatitis B: can the fracture risk assessment tool identify those at greatest risk? J Infect Dis 2014; 211:374-82. [PMID: 25156561 DOI: 10.1093/infdis/jiu471] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) is an established nucleotide analogue in the treatment of chronic hepatitis B. Bone mineral density loss has been described in TDF-treated patients with human immunodeficiency virus infection, but limited data exist for patients with chronic hepatitis B. Dual X-ray absorptiometry (DEXA) was used to determine bone mineral density changes in TDF-exposed patients. We evaluated the accuracy of the Fracture Risk Assessment Tool (FRAX) as an alternative to DEXA in clinical practice. METHODS A total of 170 patients were studied: 122 were exposed to TDF, and 48 were controls. All patients underwent DEXA, and demographic details were recorded. FRAX scores (before and after DEXA) were calculated. RESULTS TDF was associated with a lower hip T score (P = .02). On univariate and multivariate analysis, advancing age, smoking, lower body mass index, and TDF exposure were independent predictors of low bone mineral density. In addition, the pre-DEXA FRAX score was an accurate predictor of the post-DEXA FRAX treatment recommendation (100% sensitivity and 83% specificity), area under the curve 0.93 (95% CI, .87-.97, P < .001). CONCLUSIONS TDF-treated patients with chronic hepatitis B have reduced bone mineral density, but the reduction is limited to 1 anatomical site. Age and advanced liver disease are additional contributing factors, underlining the importance of multifactorial fracture risk assessment. FRAX can accurately identify those at greatest risk of osteoporotic fracture.
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Affiliation(s)
- Upkar S Gill
- Hepatology Unit, Centre for Digestive Diseases, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
| | | | | | | | - Mark J W McPhail
- Department of Hepatology, Faculty of Medicine, Imperial College London, St Mary's Hospital, Paddington
| | - David A Barr
- Department of Infectious Diseases, Brownlee Centre for Infectious and Communicable Diseases, NHS Greater Glasgow and Clyde, United Kingdom
| | | | | | - Paul Kooner
- Department of Hepatology, Barts Health NHS Trust
| | - Graham R Foster
- Hepatology Unit, Centre for Digestive Diseases, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
| | - Patrick T F Kennedy
- Hepatology Unit, Centre for Digestive Diseases, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
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Mateo L, Holgado S, Mariñoso ML, Pérez-Andrés R, Bonjoch A, Romeu J, Olivé A. Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients. Clin Rheumatol 2014; 35:1271-9. [DOI: 10.1007/s10067-014-2627-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 04/11/2014] [Accepted: 04/11/2014] [Indexed: 01/19/2023]
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Kasonde M, Niska RW, Rose C, Henderson FL, Segolodi TM, Turner K, Smith DK, Thigpen MC, Paxton LA. Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana. PLoS One 2014; 9:e90111. [PMID: 24625530 PMCID: PMC3953113 DOI: 10.1371/journal.pone.0090111] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 01/27/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis (PrEP) has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD) loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women. METHOD We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18-29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA) scans at the hip, spine, and forearm. RESULTS A total of 220 participants (108 TDF-FTC, 112 placebo) had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8%) participants had low baseline BMD (z-score of <-2.0 at any anatomic site), including 3/114 women (2.6%) and 12/106 men (11.3%) (p = 0.02). Low baseline BMD was associated with being underweight (p = 0.02), having high blood urea nitrogen (p = 0.02) or high alkaline phosphatase (p = 0.03), and low creatinine clearance (p = 0.04). BMD losses of >3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0%) TDF-FTC vs. 26/79 (32.9%) placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm -0.84% (p = 0.01), spine -1.62% (p = 0.0002), hip -1.51% (p = 0.003)]. CONCLUSION Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons. TRIAL REGISTRATION ClinicalTrials.gov NCT00448669.
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Affiliation(s)
- Michael Kasonde
- Centers for Disease Control and Prevention- Botswana, HIV Prevention Research Unit, Gaborone, Botswana
| | - Richard W. Niska
- Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, Georgia, United States of America
| | - Charles Rose
- Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, Georgia, United States of America
| | - Faith L. Henderson
- Centers for Disease Control and Prevention- Botswana, HIV Prevention Research Unit, Gaborone, Botswana
| | - Tebogo M. Segolodi
- Centers for Disease Control and Prevention- Botswana, HIV Prevention Research Unit, Gaborone, Botswana
| | - Kyle Turner
- Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, Georgia, United States of America
| | - Dawn K. Smith
- Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, Georgia, United States of America
| | - Michael C. Thigpen
- Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, Georgia, United States of America
| | - Lynn A. Paxton
- Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, Georgia, United States of America
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Bone scintigraphy and secondary osteomalacia due to nephrotoxicity in a chronic hepatitis B patient treated with tenofovir. Rev Esp Med Nucl Imagen Mol 2014. [DOI: 10.1016/j.remnie.2014.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Tourret J, Deray G, Isnard-Bagnis C. Tenofovir effect on the kidneys of HIV-infected patients: a double-edged sword? J Am Soc Nephrol 2013; 24:1519-27. [PMID: 24052632 DOI: 10.1681/asn.2012080857] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Tenofovir disoproxil fumarate (TDF), the first nucleotidic inhibitor of HIV reverse transcription, became available in 2001. It has been extensively used worldwide and is now the most prescribed antiretroviral (ARV) drug. Its high antiviral activity and favorable metabolic profile are responsible for its success. Furthermore, TDF has been associated with other ARVs to form new combined antiretroviral treatments in only one tablet once-a-day, which increases treatment adherence. Fears of potential nephrotoxicity that tenofovir would have in common with two other drugs from the same family (adefovir, used to treat hepatitis B, and cidofovir, used to treat cytomegalovirus infections) were alleviated by the early clinical trials. Yet, in 2001, the first case of TDF-induced acute nephrotoxicity was published. Numerous cases have been published since then, and it is now established that TDF presents a tubular toxicity risk. Some facilitating factors have been identified, such as co-prescription of didanosine or boosted protease inhibitor, preexisting CKD, low body weight, and associated diabetes mellitus. Conversely, whether TDF is nephrotoxic in the long term is a highly debated question. Some studies suggest a decreased GFR when TDF is prescribed for a long period, while others indicate that TDF is safe for the kidneys even after many years of use. Here we review the differences in patient characteristics, study designs, and measured outcomes that can possibly explain these conflicting findings. We conclude with rational recommendation for appropriate TDF prescription.
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Affiliation(s)
- Jérôme Tourret
- Nephrology Department, Groupe Hospitalo-Universitaire Pitié-Salpêtrière and Université Pierre et Marie Curie, Paris, France
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Avihingsanon A, Apornpong T, Ramautarsing RA, Ubolyam S, Tangkijvanich P, Ananworanich J, Lange JMA, Matthews G, Lewin SR, Ruxrungtham K. Decline in serum 25 hydroxyvitamin D levels in HIV-HBV-coinfected patients after long-term antiretroviral therapy. Antivir Ther 2013; 19:41-9. [PMID: 23970149 DOI: 10.3851/imp2673] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND Vitamin D insufficiency plays an important role in the development of fibrosis in chronic liver disease. METHODS This was a cross-sectional study from Thailand. Liver fibrosis was assessed by transient elastography. Serum 25 hydroxyvitamin D (25[OH]D)<30 ng/ml was defined as hypovitaminosis D. 25(OH)D was assessed prior to and following tenofovir disoproxil fumarate (TDF). Factors related to 25(OH)D levels were determined by logistic regression analysis. RESULTS A total of 158 HIV-HBV-coinfected patients (32% female, median age 43 years) were included. Overall, liver disease was mild with 13.4% having a fibrosis score (FS) of 7.1-14 kPa and 2% with a FS>14 kPa. Median (IQR) duration on TDF was 5 years (4-7). The median estimated glomerular filtration rate was 96.9 ml/min/1.73 m(2). The median (IQR) serum 25(OH)D levels prior to and following TDF were 24.8 ng/ml (21.3-30.6) and 22.8 ng/ml (18.0-27.7), respectively; P≤0.001). The proportion of patients with hypovitaminosis D significantly increased from 72.2% (95% CI 64.7, 78.6) prior to TDF to 84.2% (95% CI 77.7, 89.0) after taking TDF (P=0.01). Factors associated with hypovitaminosis D by multivariate analysis were female sex (adjusted OR 3.8, 95% CI 1.1, 13.7; P=0.038) and duration of antiretroviral therapy (ART)>5 years (OR 3.3, 95% CI 1.2, 8.8; P=0.017). Vitamin D levels were not associated with significant liver fibrosis. CONCLUSIONS Although our HIV-HBV-coinfected patients live in the tropics, there was a high prevalence of hypovitaminosis D, especially in female patients and those receiving prolonged ART. Since HIV-HBV-coinfection requires long-term use of the HBV-active drug, TDF, which can also contribute to bone loss, routine vitamin D assessment and supplementation as necessary should be considered.
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Affiliation(s)
- Anchalee Avihingsanon
- HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand
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Gómez Martinez MV, Gallardo FG, Pirogova T, García-Samaniego J. Bone scintigraphy and secondary osteomalacia due to nephrotoxicity in a chronic hepatitis B patient treated with tenofovir. Rev Esp Med Nucl Imagen Mol 2013; 33:103-5. [PMID: 23920225 DOI: 10.1016/j.remn.2013.05.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Revised: 05/28/2013] [Accepted: 05/30/2013] [Indexed: 12/17/2022]
Abstract
Tenofovir is a nucleotide analogue used for the treatment of chronic hepatitis B and HIV infection. The safety of tenofovir is high but it has been described that tenofovir produces tubular toxicity and Fanconi's syndrome in some HIV-infected patients. To our knowledge this is the first documented case of bone involvement in Fanconi's syndrome in a patient treated with tenofovir for chronic hepatitis B without HIV coinfection. Bone scintigraphy has proven to be very useful for the diagnosis of secondary osteomalacia. Normalization of the bone scan after the withdrawal of the drug and the decline in alkaline phosphatase and phosphate serum levels reinforce the cause-effect relationship.
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Affiliation(s)
- M V Gómez Martinez
- Servicio de Medicina Nuclear y Unidad de Hepatología, Hospital Carlos III, Centro de Investigación Biomédica en Red de Enfermedades y Digestivas (CIBERehd), Madrid, Spain.
| | - F G Gallardo
- Servicio de Medicina Nuclear y Unidad de Hepatología, Hospital Carlos III, Centro de Investigación Biomédica en Red de Enfermedades y Digestivas (CIBERehd), Madrid, Spain
| | - T Pirogova
- Servicio de Medicina Nuclear y Unidad de Hepatología, Hospital Carlos III, Centro de Investigación Biomédica en Red de Enfermedades y Digestivas (CIBERehd), Madrid, Spain
| | - J García-Samaniego
- Servicio de Medicina Nuclear y Unidad de Hepatología, Hospital Carlos III, Centro de Investigación Biomédica en Red de Enfermedades y Digestivas (CIBERehd), Madrid, Spain
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Klassen K, Martineau AR, Wilkinson RJ, Cooke G, Courtney AP, Hickson M. The effect of tenofovir on vitamin D metabolism in HIV-infected adults is dependent on sex and ethnicity. PLoS One 2012; 7:e44845. [PMID: 22984574 PMCID: PMC3440360 DOI: 10.1371/journal.pone.0044845] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2012] [Accepted: 08/08/2012] [Indexed: 11/19/2022] Open
Abstract
Background Tenofovir has been associated with renal phosphate wasting, reduced bone mineral density, and higher parathyroid hormone levels. The aim of this study was to carry out a detailed comparison of the effects of tenofovir versus non-tenofovir use on calcium, phosphate and, vitamin D, parathyroid hormone (PTH), and bone mineral density. Methods A cohort study of 56 HIV-1 infected adults at a single centre in the UK on stable antiretroviral regimes comparing biochemical and bone mineral density parameters between patients receiving either tenofovir or another nucleoside reverse transcriptase inhibitor. Principal Findings In the unadjusted analysis, there was no significant difference between the two groups in PTH levels (tenofovir mean 5.9 pmol/L, 95% confidence intervals 5.0 to 6.8, versus non-tenofovir; 5.9, 4.9 to 6.9; p = 0.98). Patients on tenofovir had significantly reduced urinary calcium excretion (median 3.01 mmol/24 hours) compared to non-tenofovir users (4.56; p<0.0001). Stratification of the analysis by age and ethnicity revealed that non-white men but not women, on tenofovir had higher PTH levels than non-white men not on tenofovir (mean difference 3.1 pmol/L, 95% CI 5.3 to 0.9; p = 0.007). Those patients with optimal 25-hydroxyvitamin D (>75 nmol/L) on tenofovir had higher 1,25-dihydroxyvitamin D [1,25(OH)2D] (median 48 pg/mL versus 31; p = 0.012), fractional excretion of phosphate (median 26.1%, versus 14.6; p = 0.025) and lower serum phosphate (median 0.79 mmol/L versus 1.02; p = 0.040) than those not taking tenofovir. Conclusions The effects of tenofovir on PTH levels were modified by sex and ethnicity in this cohort. Vitamin D status also modified the effects of tenofovir on serum concentrations of 1,25(OH)2D and phosphate.
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Affiliation(s)
- Karen Klassen
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
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Brown TT, Ross AC, Storer N, Labbato D, McComsey GA. Bone turnover, osteoprotegerin/RANKL and inflammation with antiretroviral initiation: tenofovir versus non-tenofovir regimens. Antivir Ther 2012; 16:1063-72. [PMID: 22024522 DOI: 10.3851/imp1874] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Bone mineral density decreases with antiretroviral therapy (ART) initiation, although the pathogenesis, including the role of tenofovir (TDF), is unclear. This study assessed changes in bone-turnover markers, osteoprotegerin (OPG), soluble receptor activator for nuclear factor-κβ ligand (sRANKL), and inflammation in subjects initiating TDF- versus non-TDF-containing regimens, and determined the relationship between bone turnover, OPG/sRANKL and inflammation. METHODS This was a longitudinal observational study comparing levels of bone turnover markers (C-terminal telopeptide of type I collagen [CTX] and osteocalcin [OC]), OPG, sRANKL and inflammatory cytokines (soluble tumour necrosis factor [TNF]-α receptor [sTNFR]-I, sTNFR-II and interleukin-6) prior to ART and 6-12 months after ART initiation with a TDF- versus non-TDF-containing regimen in HIV-infected subjects 18-50 years old. RESULTS A total of 87 subjects were enrolled (TDF n=44 and non-TDF n=43). Groups were similar except subjects on TDF had a lower CD4(+) T-cell nadir (P<0.01) and were more likely to receive a protease inhibitor (PI; P=0.03). At pre-ART, 35% and 1% of subjects had CTX and OC above the normal range, respectively. Both increased with ART initiation, whereas OPG, sRANKL and inflammatory markers significantly decreased. In multivariate models, increases in OC were associated with TDF use, PI use and pre-ART levels of sTNFR-I, whereas increases in CTX were associated with CD4(+) T-cell nadir <50 cell/mm³. Increases in bone markers were unrelated to pre-ART levels of OPG/sRANKL and changes in OPG/sRANKL after ART initiation. CONCLUSIONS TDF use, PI use, TNF-α activity and advanced HIV disease are associated with changes in bone turnover markers, underscoring the complicated interaction between ART, bone turnover, inflammation and immune status, which extend beyond the OPG/RANKL system.
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Affiliation(s)
- Todd T Brown
- Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
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Kumar N, Bower M, Nelson M. Severe vitamin D deficiency in a patient treated for hepatitis B with tenofovir. Int J STD AIDS 2012; 23:59-60. [DOI: 10.1258/ijsa.2009.009502] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
With the increasing use of tenofovir disoproxil in the management of HIV and hepatitis B, serious adverse effects, such as renal dysfunction, will inevitably increase in frequency. We describe a case of a patient presenting with hypophosphataemia suggestive of Fanconi's syndrome, but in fact explicable by simple vitamin D deficiency. This emphasizes that while monitoring for adverse effects is recommended, physicians must consider all alternative causes for biochemical abnormalities prior to discontinuing tenofovir and delaying appropriate management.
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Affiliation(s)
| | - M Bower
- Department of Medical Oncology
| | - M Nelson
- Department of HIV Medicine, Chelsea and Westminster Hospital, London, UK
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Liu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, Thompson M, Grant R, Pathak S, O'Hara B, Gvetadze R, Chillag K, Grohskopf L, Buchbinder SP. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One 2011; 6:e23688. [PMID: 21897852 PMCID: PMC3163584 DOI: 10.1371/journal.pone.0023688] [Citation(s) in RCA: 134] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2011] [Accepted: 07/22/2011] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco. METHODS/FINDINGS We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13). CONCLUSIONS Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures. TRIAL REGISTRATION ClinicalTrials.gov: NCT00131677.
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Affiliation(s)
- Albert Y Liu
- San Francisco Department of Public Health, San Francisco, California, United States of America.
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Rebolledo BJ, Unnanuntana A, Lane JM. Bilateral pathologic hip fractures associated with antiretroviral therapy: a case report. J Bone Joint Surg Am 2011; 93:e78. [PMID: 21792481 DOI: 10.2106/jbjs.j.00885] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Brian J Rebolledo
- Weill Cornell Medical College, Cornell University, 1300 East 70th Street, New York, NY 10021, USA.
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Abstract
Tenofovir is an acyclic nucleotide analogue reverse-transcriptase inhibitor structurally similar to the nephrotoxic drugs adefovir and cidofovir. Tenofovir is widely used to treat HIV infection and approved for treatment of hepatitis B virus. Despite initial cell culture and clinical trials results supporting the renal safety of tenofovir, its clinical use is associated with a low, albeit significant, risk of kidney injury. Proximal tubular cell secretion of tenofovir explains the accumulation of the drug in these mitochondria-rich cells. Tenofovir nephrotoxicity is characterized by proximal tubular cell dysfunction that may be associated with acute kidney injury or chronic kidney disease. Withdrawal of the drug leads to improvement of analytical parameters that may be partial. Understanding the risk factors for nephrotoxicity and regular monitoring of proximal tubular dysfunction and serum creatinine in high-risk patients is required to minimize nephrotoxicity. Newer, structurally similar molecular derivatives that do not accumulate in proximal tubules are under study.
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Normal plasma FGF23 levels kinetic in tenofovir-related hypophosphatemic osteomalacia in an HIV-infected patient with von Recklinghausen disease. Joint Bone Spine 2011; 78:306-8. [DOI: 10.1016/j.jbspin.2010.11.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2010] [Accepted: 11/03/2010] [Indexed: 11/22/2022]
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Pérez-Rivera AA, Sáez P, León E, Lozano de León-Naranjo F. Mujer con infección por el VIH, intensos dolores osteomusculares y debilidad generalizada. Enferm Infecc Microbiol Clin 2011; 29:308-10. [DOI: 10.1016/j.eimc.2010.07.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2010] [Revised: 07/08/2010] [Accepted: 07/12/2010] [Indexed: 10/18/2022]
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Abstract
Second generation nucleos (t) idic analogues result in a complete viral suppression after 48 to 96 weeks of therapy in most patients, regardless of the virus (HBV genotype, wild type or pre-C mutant), the underlying liver disease (cirrhosis or not) or the immune status (mono- or HIV/HBV co-infection). This antiviral efficacy may result in HBe or HBs seroconversion. Its clinical impact is important since inactivation of necroinflammation allows, in the absence of liver comorbidities, a stabilisation then a reversal of fibrosis and cirrhosis, and consequently a decrease in the occurrence of carcinomatous or non-carcinomatous complications. The future issues for long-term anti-HBV therapy will be adherence on the one hand and safety on the other hand. Therapeutic failures are mainly related to poor adherence more than to viral resistance. Adherence of patients has to be optimized by therapeutic education and education of physicians. Long-term safety has to be systematically evaluated. More than the neuromuscular or metabolic side effects (lactic acidosis), the renal and bone-related adverse events have to be monitored, followed-up and anticipated by good clinical practices.
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Affiliation(s)
- S Pol
- Unité d'Hépatologie, Inserm U-567 et Université Paris V (René Descartes), Hôpital Cochin, Paris, France.
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Jhaveri MA, Mawad HW, Thornton AC, Mullen NW, Greenberg RN. Tenofovir-Associated Severe Bone Pain: I Cannot Walk! ACTA ACUST UNITED AC 2010; 9:328-34. [DOI: 10.1177/1545109710376595] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
| | - Hanna W. Mawad
- University of Kentucky School of Medicine, Lexington, KY, USA
| | | | | | - Richard N. Greenberg
- University of Kentucky School of Medicine, Lexington, KY, USA, Lexington VA Medical Center, Lexington, KY, USA,
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Abstract
Highly active antiretroviral therapy (HAART) has had a profound impact on improving the long-term prognosis for individuals infected with human immunodeficiency virus (HIV). HAART has been available for close to two decades, and now a significant number of patients with access to HAART are over the age of 50 years. Many clinical studies have indicated that HIV infection, as well as components of HAART, can increase the risk in these individuals to a variety of noninfectious complications, including a risk to bone health. There is a significant need for detailed mechanistic analysis of the aging, HIV-infected population regarding the risk of HIV infection and therapy in order to maintain bone health. Insights from basic mechanistic studies will help to shed light on the role of HIV infection and the components of HAART that impact bone health, and will help in identifying preventative countermeasures, particularly for individuals 50 years of age and older.
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Affiliation(s)
- Kim C Mansky
- Division of Orthodontics, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
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Estrella MM, Fine DM, Atta MG. Recent developments in HIV-related kidney disease. ACTA ACUST UNITED AC 2010; 4:589-603. [PMID: 21331321 DOI: 10.2217/hiv.10.42] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Although kidney disease has been a recognized complication of HIV infection since the beginning of the HIV epidemic, its epidemiology, underlying causes and treatment have evolved in developed countries where HAART has been widely available. HIV-associated nephropathy and HIV immune complex-mediated kidney disease were the prominent renal diagnoses in the earlier period of the HIV epidemic. While HIV immune complex-mediated kidney disease remains a common finding among HIV-infected individuals with kidney disease, the incidence of HIV-associated nephropathy has been diminishing in developed countries. The role of the metabolic effects of long-term HAART exposure and nephrotoxicity of certain antiretroviral medications on the development and progression of chronic kidney disease is now of increasing concern. The long-term clinical implications of acute kidney injury among HIV-infected persons are increasingly recognized. Kidney disease in HIV-infected persons continues to be a major risk factor for morbidity and mortality in this patient population; therefore, early recognition and treatment of kidney disease are imperative in lessening the impact of kidney disease on the health of HIV-infected individuals. This review focuses on recent developments and ongoing challenges in the understanding, diagnosis and management of HIV-related kidney disease.
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Affiliation(s)
- Michelle M Estrella
- Johns Hopkins University School of Medicine, Division of Nephrology, 1830 E Monument Street, Suite 416, Baltimore, MD 21205, USA
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40
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Duarte-Rojo A, Heathcote EJ. Efficacy and safety of tenofovir disoproxil fumarate in patients with chronic hepatitis B. Therap Adv Gastroenterol 2010; 3:107-19. [PMID: 21180595 PMCID: PMC3002569 DOI: 10.1177/1756283x09354562] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Chronic hepatitis B (CHB) is prevalent worldwide. It may cause cirrhosis and hepatocellular carcinoma. Treatment for this condition may need to be lifelong, thus the drugs used must be both efficacious and safe. Clinical trials of tenofovir have demonstrated a good safety profile for this drug and it has potent antiviral properties. However, to better characterize the safety of this drug, the postmarketing surveillance must be taken into account. Clinicians need to be vigilant, as infrequent adverse events may be revealed during this phase. The current review presents a detailed exposé of preclinical and clinical data on tenofovir to increase awareness of possible adverse events and drug-drug interactions, based on the large experience of this drug in human immunodeficiency virus (HIV) treatment (and to date in patients with CHB). Several recommendations that may help the clinician to prevent the development of adverse events associated with tenofovir disoproxil fumarate (TDF) treatment are outlined, along with a suggested surveillance protocol for the timely and proper identification of possible renal and bone toxicity.
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Affiliation(s)
- Andrés Duarte-Rojo
- Liver Centre, Toronto Western Hospital, University Health Network / University of Toronto. Toronto, Ontario, Canada
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