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The unexpected high prevalence of HBV subgenotype D4 in patients with chronic hepatitis B in Galicia, a northwestern Spanish region, reflects strong links with Latin America. J Clin Virol 2022; 153:105195. [PMID: 35661583 DOI: 10.1016/j.jcv.2022.105195] [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: 03/09/2022] [Revised: 05/09/2022] [Accepted: 05/28/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) comprises 9 genotypes and multiple subgenotypes that depict differences in geographic distribution, clinical outcome and response to antiviral therapy. However, the molecular epidemiology of HBV geno/subgenotypes is globally scarce. In Spain, HBV genotype D seems to be more prevalent in the northwestern regions compared to the rest of the country for unclear reasons. METHODS HBV genotyping was performed using geno2pheno on a S gene fragment amplified from plasma collected from all chronic hepatitis B individuals attended at one reference hospital in Santiago de Compostela, the Galicia's capital town. Phylogenetic and phylogeographic analyses using a fragment of 345 bp were performed in all viremic specimens. To avoid misleading allocation as consequence of short fragment analysis, several bioinformatic controls were used. RESULTS A total of 320 individuals with persistent serum HBsAg+ and detectable HBV-DNA were seen between 2000 and 2016 (male 68.4%; median age, 52 years-old; native Spaniards 83.8%). HBV genotype distribution was as follows: A 15.3%; B 1.6%; C 2.5%; D 71.6%; E 3.1%; F 2.2%; G 3.1%; and H 0.6%. HBV genotype D was mostly represented by D4 and D2 subgenotypes (33.4% and 15% of total, respectively). Compared to chronic hepatitis B patients with genotypes B, C, E and G, HBV-D4 carriers tended to be older (54.2% had >50 years-old) and HBeAg-negative (85%). Moreover, 43% were female, 4.7% had cirrhosis, 10.2% hepatitis C and 6.4% HIV coinfection. Phylogenetic analyses could be performed on 82 HBV-D4 specimens; and 79 were confirmed as HBV-D4 using PhyML. Phylogeography using FasTree suggested at least two distinct introductions of HBV-D4 in Galicia, one from the Caribbean and South America, and another from India. CONCLUSIONS HBV subgenotype D4 is the most prevalent HBV variant in chronic hepatitis B patients living in the northwest of Spain, representing 33.4% (107/320) of all chronic hepatitis B infections. This rate of HBV-D4 is among the highest reported worldwide. Epidemiological and phylogenetic analyses suggest a strong association with historical migrant exchanges with Latin America, and especially with the Caribbean basin.
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Sultana C, Casian M, Oprea C, Ianache I, Grancea C, Chiriac D, Ruta S. Hepatitis B Virus Genotypes and Antiviral Resistance Mutations in Romanian HIV-HBV Co-Infected Patients. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:531. [PMID: 35454370 PMCID: PMC9028173 DOI: 10.3390/medicina58040531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/01/2022] [Accepted: 04/07/2022] [Indexed: 11/16/2022]
Abstract
Background and Objectives: Romania has one of the highest prevalence of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV) patients, mostly in those parenterally infected during childhood; nevertheless, there are scarce data on the virological profile of co-infection. The objective of this study was to assess the prevalence of HBV genotypes and antiviral resistance-associated mutations (RAMs) in these co-infected patients, in order to monitor the viral factors associated with the evolution of liver disease. Materials and Methods: HBV genotypes and RAMs were detected using nested PCR and line probe assays (INNO-LiPA HBV genotyping assay, and INNO-LiPA HBV DR v2, Innogenetics). Results: Out of 117 co-infected patients, 73.5% had detectable HBV-DNA, but only 38.5% presented an HBV viral load >1000 IU/mL. HBV genotype A was present in 66.7% of the cases and was dominant in patients parenterally infected during early childhood, who experienced multiple treatment regimens, with a mean therapy length of 15.25 years, and present numerous mutations associated with lamivudine (LAM) resistance, but very rarely active liver disease. HBV genotype D was detected in 33.3% of the cases, mostly in recently diagnosed injecting drug users who are treatment naïve, but, nevertheless, present RAMs in 63.5% of the cases, suggesting transmitted drug resistance, and display more frequently advanced liver fibrosis (36.1% vs. 12.3%; p = 0.033). The most frequently encountered RAMs are M204V/I: 48.8%, L180M: 33.3%, L80V: 28.8%, and V173L: 42.2%. There are no significant differences in the distribution of RAMs in patients infected with different HBV genotypes, except for the L80V and N236T mutations, which were more frequently found in HBV genotype A infections (p = 0.032 and p = 0.004, respectively). Conclusions: HBV genotypes A and D are the only genotypes present in HIV−HBV co-infected patients from Romania, with different distributions according to the infection route, and are frequently associated with multiple RAMs, conferring extensive resistance to LAM.
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Affiliation(s)
- Camelia Sultana
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.C.); (C.O.); (S.R.)
- Emergent Diseases Department, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (C.G.); (D.C.)
| | - Mihnea Casian
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.C.); (C.O.); (S.R.)
- Cardiology Department II, Dr Carol Davila Central Military Emergency Hospital, 010825 Bucharest, Romania
| | - Cristiana Oprea
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.C.); (C.O.); (S.R.)
- HIV/SIDA Department I, Dr Victor Babes Hospital of Infectious and Tropical Diseases, 030303 Bucharest, Romania;
| | - Irina Ianache
- HIV/SIDA Department I, Dr Victor Babes Hospital of Infectious and Tropical Diseases, 030303 Bucharest, Romania;
| | - Camelia Grancea
- Emergent Diseases Department, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (C.G.); (D.C.)
| | - Daniela Chiriac
- Emergent Diseases Department, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (C.G.); (D.C.)
| | - Simona Ruta
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.C.); (C.O.); (S.R.)
- Emergent Diseases Department, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (C.G.); (D.C.)
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Zhou K, Terrault NA. Treatment of HCV, HDV, or HIV Coinfections. HEPATITIS B VIRUS AND LIVER DISEASE 2021:339-373. [DOI: 10.1007/978-981-16-3615-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Abstract
INTRODUCTION Occult hepatitis B virus (HBV) infection, so-called occult B infection (OBI), is defined by the recognition of HBV-DNA in the absence of serum hepatitis B surface antigen (HBsAg). The HBV-DNA genome in OBI is fully replication competent and produced in the liver, characteristically with low-level HBV-DNA fluctuations in the bloodstream. The OBI status remains between chronic (HBsAg +) and resolved (anti-HBs +) phases in the natural history of HBV infection. METHODS The clinical interest in OBI has increased because of its potential for overt HBV reactivation under immunosuppression as well as for HBV transmission, well established in recipients of blood transfusions and/or organ transplants. RESULTS Given the shared transmission routes for HIV and HBV, earlier reports claimed that OBI was more frequent in AIDS patients. By contrast, the current scenario shows that OBI is negligible in the HIV population. One explanation is that HBV immunization and recall vaccination campaigns have been very active in this group. A second and most important reason points to the wide use of antiretroviral regimens that include anti-HBV active agents, that is, tenofovir, lamivudine, and/or emtricitabine. They are recommended either as treatment for all HIV carriers or as pre-exposure prophylaxis for uninfected individuals at risk. The consequences are that HBV reactivations associated with HIV-related immunodeficiency have become very rare. Furthermore, HBV suppression with these antivirals has markedly reduced the likelihood of transmission from OBI carriers and/or acquisition by uninfected exposed individuals. CONCLUSION Enthusiasm unabated, however, new tenofovir-sparing antiretroviral regimens are becoming popular and might account for a resurgence of OBI in the HIV setting.
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Coffin CS, Terrault NA. Treatment of HCV, HDV, or HIV Coinfection. HEPATITIS B VIRUS AND LIVER DISEASE 2018:239-262. [DOI: 10.1007/978-981-10-4843-2_13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Boyd A, Lacombe K, Lavocat F, Miailhes P, Lascoux-Combe C, Girard PM, Zoulim F. Low incidence of precore W28* mutant variants in treated hepatitis B virus and human immunodeficiency virus co-infected patients. Antiviral Res 2017; 149:174-178. [PMID: 29169914 DOI: 10.1016/j.antiviral.2017.11.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 11/15/2017] [Accepted: 11/16/2017] [Indexed: 12/23/2022]
Abstract
The precore (pc) W28* mutation arises from immune-selective pressures during the hepatitis B "e" antigen (HBeAg)-positive phase of chronic hepatitis B virus (HBV) infection and has been linked to severe liver-related morbidity. Here, we examined the determinants of harboring this mutation and its rate of emergence in treated patients co-infected with human immunodeficiency virus (HIV) and HBV. In a three-year prospective cohort of 165 HIV-HBV co-infected patients, pcW28* mutation was determined via DNA-chip during yearly sampling. In a subgroup with liver biopsies, HBV covalently-closed circular (ccc)-DNA and total intrahepatic (IH)-DNA were quantified by real-time PCR. From respective inclusion to year-3 visits, median HBV-DNA levels decreased (5.88 log10 IU/mL to <1.78 log10 IU/mL, p < 0.001) and tenofovir-use increased (15.8%-71.4%, p < 0.001). At baseline, 47 of 162 (29.0%) patients had the pcW28* mutation and were more frequently HBeAg-negative (adjusted-OR = 4.37, 95%CI = 1.76-10.86) and had non-A HBV genotypes (adjusted-OR = 9.14, 95%CI = 4.05-20.66). No association with HIV-related factors was observed. In 114 patients without baseline mutation and available data, four developed incident pcW28* mutation by the end of follow-up (cumulative 3.5%, 95%CI = 1.3-9.1%). In the 32 patients with liver biopsies, 10 (31.3%) patients harboring the pcW28* mutation had significantly lower adjusted mean cccDNA (0.05 versus without = 0.43 copies/cell, p < 0.001) and total IH-DNA levels (2.31 versus without = 18.59 copies/cell, p = 0.006). In conclusion, the pcW28* mutation infrequently appeared in this co-infected study population with increased use of potent antivirals and suppressed levels of circulating virus.
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Affiliation(s)
- Anders Boyd
- INSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F75012, Paris, France
| | - Karine Lacombe
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), F75012, Paris, France; Service des maladies infectieuses et tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Fabien Lavocat
- Cancer Research Center of Lyon, INSERM, Unité 1052, CNRS, UMR 5286, Université de Lyon, Lyon, France
| | - Patrick Miailhes
- Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France
| | - Caroline Lascoux-Combe
- Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, APHP, Paris, France
| | - Pierre-Maire Girard
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), F75012, Paris, France; Service des maladies infectieuses et tropicales, Hôpital Saint-Antoine, AP-HP, Paris, France
| | - Fabien Zoulim
- Cancer Research Center of Lyon, INSERM, Unité 1052, CNRS, UMR 5286, Université de Lyon, Lyon, France; Hepatology Department, Hospices Civils de Lyon, Lyon, France.
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Bihl F, Martinetti G, Wandeler G, Weber R, Ledergeber B, Calmy A, Battegay M, Cavassini M, Vernazza P, Caminada AP, Rickenbach M, Bernasconi E. HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons. BMC Gastroenterol 2015; 15:79. [PMID: 26152237 PMCID: PMC4495698 DOI: 10.1186/s12876-015-0308-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Accepted: 06/24/2015] [Indexed: 12/24/2022] Open
Abstract
Background Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. Methods HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA <20 IU/mL) and the influence of HBV genotypes were determined. Results 143 HIV/HBV-coinfected participants with detectable HBV DNA were identified. The predominant HBV genotypes were A (82 patients, 57 %); and D (35 patients, 24 %); 20 patients (14 %) were infected with multiple genotypes (3 % A + D and 11 % A + G); and genotypes B, C and E were each present in two patients (1 %). TDF completely suppressed HBV DNA in 131 patients (92 %) within 6 months; and in 12 patients (8 %), HBV DNA suppression was delayed. No HBV resistance mutations to TDF were found in patients with delayed response, but all were infected with HBV genotype A (among these, 5 patients with genotype A + G), and all had previously been exposed to lamivudine. Conclusion In HIV/HBV-coinfected patients, infection with multiple HBV genotypes was more frequent than previously reported. The large majority of patients had an undetectable HBV viral load at six months of TDF-containing ART. In patients without viral suppression, no TDF-related resistance mutations were found. The role of specific genotypes and prior lamivudine treatment in the delayed response to TDF warrant further investigation.
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Affiliation(s)
- Florian Bihl
- Cantonal Hepatobiliary Unit, Ente Ospedaliera Cantonale, Ospedale San Giovanni Bellinzona,Switzerland and Gastroenterology and Hepatology Service, University Hospital of Geneva, Geneva, Switzerland.
| | - Gladys Martinetti
- Institute of Microbiology, Ente Ospedaliera Cantonale, Bellinzona, Switzerland.
| | - Gilles Wandeler
- Department of Infectious Diseases, University Hospital of Bern, and Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
| | - Rainer Weber
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
| | - Bruno Ledergeber
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
| | - Alexandra Calmy
- Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland.
| | - Manuel Battegay
- Division of Infectious Diseases, University Hospital of Basel, Basel, Switzerland.
| | - Matthias Cavassini
- Division of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland.
| | - Pietro Vernazza
- Division of Infectious Diseases, Cantonal Hospital of S. Gallen, St. Gallen, Switzerland.
| | - Anna-Paola Caminada
- Institute of Microbiology, Ente Ospedaliera Cantonale, Bellinzona, Switzerland.
| | | | - Enos Bernasconi
- Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland.
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Pal A, Sarkar N, Saha D, Guha SK, Saha B, Chakrabarti S, Chakravarty R. High incidence of lamivudine-resistance-associated vaccine-escape HBV mutants among HIV-coinfected patients on prolonged antiretroviral therapy. Antivir Ther 2015; 20:545-54. [PMID: 25654813 DOI: 10.3851/imp2942] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/29/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Worldwide, frequent emergence of lamivudine (3TC)-resistant HBV mutants has been reported in HIV-HBV-coinfected patients during long-term antiretroviral therapy (ART) that contains 3TC as the sole anti-HBV drug. Three major patterns of mutations in HBV polymerase gene, namely single (rtM204V), double (rtL180M+rtM204V) and triple (rtV173L+rtL180M+rtM204V) mutations, are associated with 3TC-resistance; additionally, the triple mutation has vaccine-escape potential due to a corresponding change in overlapping surface gene. Data from India, a major reservoir for HIV and HBV infection, is lacking. Here we investigated the effect of long-term 3TC treatment on virological response for HBV and characterized the 3TC-resistant HBV mutations in a cohort of HIV-HBV-coinfected patients from eastern India. METHODS A cross-sectional study was performed in HIV-infected patients (n=563) receiving 3TC-containing ART for ≥6 months from the major ART centre of eastern India during 2011-2012. The hepatitis B surface antigen-positive HIV-infected patients (n=62) were categorized into four groups with comparable sample size according to the 3TC exposure for ≥6-<12 months (group I; n=15), ≥12-<24 months (group II; n=20), ≥24-<48 months (group III; n=13) and ≥48 months (group IV; n=14). Patients' plasma samples were examined for hepatitis B e antigen (HBeAg), HBV DNA, viral load and covalently closed circular DNA (cccDNA). HBV reverse transcriptase region was sequenced. RESULTS With a longer period of 3TC exposure, the frequency of HIV-HBV-coinfected patients having HBV DNA suppression decreased. The prevalence of HBeAg-positivity, serum HBV DNA load >2,000 IU/ml and 3TC-resistant mutations simultaneously increased. Remarkably, the 3TC-resistant triple mutation predominated over the double mutation in this cohort (32.26% versus 19.34%) and prevailed in significantly higher frequency among HBV viraemic patients experiencing 3TC for ≥48 months (60% versus 10%; P=0.03). Patients with 3TC-resistant triple mutants had HBV genotype-D, high serum HBV DNA load and elevated alanine aminotransferase level, and presence of cccDNA in their serum. CONCLUSIONS Considering this alarmingly high incidence of 3TC-resistant triple mutation and its possible clinical/public health implications, proper management of 3TC-resistance among HIV-HBV-coinfected patients is an urgent necessity in India.
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Affiliation(s)
- Ananya Pal
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, India
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Aoudjane S, Chaponda M, González del Castillo AA, O'Connor J, Noguera M, Beloukas A, Hopkins M, Khoo S, van Oosterhout JJ, Geretti AM. Hepatitis B virus sub-genotype A1 infection is characterized by high replication levels and rapid emergence of drug resistance in HIV-positive adults receiving first-line antiretroviral therapy in Malawi. Clin Infect Dis 2014; 59:1618-26. [PMID: 25100867 PMCID: PMC4650769 DOI: 10.1093/cid/ciu630] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 07/30/2014] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND It has been proposed that hepatitis B virus (HBV) sub-genotype A1 infections have mild outcomes and a low risk of drug-resistance among patients infected with human immunodeficiency virus (HIV) receiving lamivudine-containing antiretroviral therapy (ART) without tenofovir in Africa. METHODS The virologic expression of HBV sub-genotype A1 coinfection was studied over 12 months in HIV-positive adults starting stavudine/lamivudine/nevirapine in Malawi, using Sanger, deep, clonal, and single full-genome sequencing for the sensitive characterization of HBV resistance-associated mutations (RAMs). RESULTS Among 1117 subjects, 133 (12%) tested HBsAg-positive. After starting ART, retention rates were 96/133 (72%) at 6 months and 54/133 (41%) at 12 months. Based upon the last available follow-up, 92/96 (96%) subjects achieved HIV-1 RNA <40 copies/mL, 48/96 (50%) showed HBV DNA <14 IU/mL, and 24/96 (25%) acquired HBV RAMs. At 6 months, M204I was detected in 8/46 (17%) and 16/17 (94%) subjects using Sanger and deep sequencing, respectively. At 12 months, all viremic patients had multiple resistance and compensatory mutations coexisting on the same HBV genomes. Comparing HBeA-positive (67/133, 50%) with HBeAg-negative subjects, 64/67 (96%) vs 35/66 (55%) showed baseline HBV DNA >2000 IU/mL (P = .0006), 39/47 (17%) vs 9/49 (82%) had persistent HBV DNA detection during follow-up (P < .0001), and 23/47 (49%) vs 2/49 (4%) acquired HBV RAMs (P < .0001). Baseline HBV DNA levels were median 8.1 vs 5.3 log10 IU/mL in subjects with vs those without treatment-emergent RAMs (P < .0001). CONCLUSIONS HBV sub-genotype A1 infections showed a severe virologic expression in HIV-positive Malawians. The findings strengthen the urgency of interventions to improve ascertainment and management of chronic hepatitis B in the region.
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Affiliation(s)
- Samir Aoudjane
- Division of Infection & Immunity and London Centre for Nanotechnology
| | - Mas Chaponda
- Department of Infectious Diseases, University of Liverpool/Malawi Liverpool Wellcome Trust, United Kingdom
| | | | - Jemma O'Connor
- Department of Infection & Population Health, University College London
| | - Marc Noguera
- IrsiCaixa & AIDS Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | | | | | - Saye Khoo
- Institute of Translational Medicine, University of Liverpool, United Kingdom
| | - Joep J. van Oosterhout
- College of Medicine, University of Malawi, Blantyre
- Dignitas International, Zomba, Malawi
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Matthews PC, Geretti AM, Goulder PJR, Klenerman P. Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in Sub-Saharan Africa. J Clin Virol 2014; 61:20-33. [PMID: 24973812 DOI: 10.1016/j.jcv.2014.05.018] [Citation(s) in RCA: 111] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2014] [Revised: 05/22/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023]
Abstract
Human immunodeficiency virus (HIV), Hepatitis B (HBV) and Hepatitis C (HCV) are blood-borne viruses with potentially shared routes of transmission. In high-income settings, the impact of antiretroviral therapy (ART) on survival has unmasked chronic liver disease from viral hepatitis B or hepatitis C as a leading cause of morbidity and mortality in individuals with HIV infection. It is now feared that progressive liver disease may threaten the success of ART programmes in developing countries, where HCV or HBV testing and monitoring are not yet systematic among HIV-infected patients and ART use is generally blind to these co-infections. We set out to review recent data from Sub-Saharan Africa, in order to build a detailed and up-to-date picture of the epidemiology and emerging impact of HBV and HCV coinfection in countries at the heart of the HIV pandemic. There is a preponderance of HIV/HBV coinfection compared to HIV/HCV in this region, and significant caveats exist regarding the accuracy of published HCV seroprevalence surveys. Morbidity and mortality of coinfection is significant, and may be further enhanced in African populations due to the influence of host, viral and environmental factors. Careful scrutiny of the coinfection problem is vital to inform an approach to directing resources, planning public health initiatives, providing clinical care, and guiding future research.
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Affiliation(s)
- Philippa C Matthews
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
| | - Anna Maria Geretti
- Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool L69 7BE, UK
| | - Philip J R Goulder
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Department of Paediatrics, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
| | - Paul Klenerman
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK; NIHR Biomedical Research Centre, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK
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[Consensus Statement by GeSIDA/National AIDS Plan Secretariat on antiretroviral treatment in adults infected by the human immunodeficiency virus (Updated January 2013)]. Enferm Infecc Microbiol Clin 2013; 31:602.e1-602.e98. [PMID: 24161378 DOI: 10.1016/j.eimc.2013.04.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2013] [Accepted: 04/08/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVE This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. METHODS To formulate these recommendations a panel composed of members of the GeSIDA/National AIDS Plan Secretariat (Grupo de Estudio de Sida and the Secretaría del Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations and the evidence which support them are based on a modification of the criteria of Infectious Diseases Society of America. RESULTS cART is recommended in patients with symptoms of HIV infection, in pregnant women, in serodiscordant couples with high risk of transmission, in hepatitisB co-infection requiring treatment, and in HIV nephropathy. cART is recommended in asymptomatic patients if CD4 is <500cells/μl. If CD4 are >500cells/μl cART should be considered in the case of chronic hepatitisC, cirrhosis, high cardiovascular risk, plasma viral load >100.000 copies/ml, proportion of CD4 cells <14%, neurocognitive deficits, and in people aged >55years. The objective of cART is to achieve an undetectable viral load. The first cART should include 2 reverse transcriptase inhibitors (RTI) nucleoside analogs and a third drug (a non-analog RTI, a ritonavir boosted protease inhibitor, or an integrase inhibitor). The panel has consensually selected some drug combinations, for the first cART and specific criteria for cART in acute HIV infection, in tuberculosis and other HIV related opportunistic infections, for the women and in pregnancy, in hepatitisB or C co-infection, in HIV-2 infection, and in post-exposure prophylaxis. CONCLUSIONS These new guidelines update previous recommendations related to first cART (when to begin and what drugs should be used), how to monitor, and what to do in case of viral failure or adverse drug reactions. cART specific criteria in comorbid patients and special situations are similarly updated.
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Roman S, Panduro A. HBV endemicity in Mexico is associated with HBV genotypes H and G. World J Gastroenterol 2013; 19:5446-5453. [PMID: 24023487 PMCID: PMC3761097 DOI: 10.3748/wjg.v19.i33.5446] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 06/15/2013] [Accepted: 07/18/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics, progression, severity of disease and antiviral response. Herein, we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico. HBV genotype H is predominant among the Mexican population, but not in Central America. Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence, apparently due to a rapid resolution of the infection, low viral loads and a high prevalence of occult B infection. During chronic infections, genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities, such as obesity, alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus. Hepatocellular carcinoma prevalence is low. Thus, antiviral therapy may differ significantly from the standard guidelines established worldwide. The high prevalence of HBV genotype G in the Americas, especially among the Mexican population, raises new questions regarding its geographic origin that will require further investigation.
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Lacombe K, Boyd A, Lavocat F, Pichoud C, Gozlan J, Miailhes P, Lascoux-Combe C, Vernet G, Girard PM, Zoulim F. High incidence of treatment-induced and vaccine-escape hepatitis B virus mutants among human immunodeficiency virus/hepatitis B-infected patients. Hepatology 2013; 58:912-22. [PMID: 23468093 DOI: 10.1002/hep.26374] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Accepted: 02/28/2013] [Indexed: 12/12/2022]
Abstract
UNLABELLED Anti-hepatitis B virus (HBV) nucleos(t)ides analogs (NA) exert selective pressures on polymerase (pol) and surface (S) genes, inducing treatment resistance and increasing the risk of vaccine escape mutants. The rate of emergence for these mutations is largely unknown in patients coinfected with human immunodeficiency virus (HIV) and HBV undergoing dual-active therapy. In a 3-year, repeat-sampling, prospective cohort study, HBV viral genome sequences of 171 HIV-HBV coinfected patients, presenting with HBV viremia for at least one visit, were analyzed every 12 months via DNA chip. Logistic and Cox proportional hazard models were used to determine risk factors specifically for S gene mutations at baseline and during follow-up, respectively. HBV-DNA levels >190 IU/mL substantially decreased from 91.8% at inclusion to 40.3% at month 36 (P < 0.001), while lamivudine (LAM) or emtricitabine (FTC) use remained steady (71.9%) and tenofovir (TDF) use expanded (month 0, 17.5%; month 36, 66.7%; P < 0.001). The largest increase of any mutation class was observed in l-nucleoside-associated pol gene/antiviral-associated S gene mutations (cumulative incidence at the end of follow-up, 17.5%) followed by alkyl phosphonate-associated pol-gene (7.4%), immune-associated S gene (specifically any amino acid change at positions s120/s145, 6.4%), and d-cyclopentane-associated pol-gene mutations (2.4%). Incidence of l-nucleoside-associated pol-gene/antiviral-associated S gene mutations was significantly associated with concomitant LAM therapy (adjusted hazard ratio [HR], 4.61; 95% confidence interval [CI], 1.36-15.56), but inversely associated with TDF use (adjusted HR/month, 0.94; 95% CI,0.89-0.98). Cumulative duration of TDF was significantly associated with a reduction in the occurrence of immune-associated S gene mutations (HR/month, 0.88; 95% CI, 0.79-0.98). No major liver-related complications (e.g., fulminant hepatitis, decompensated liver, and hepatocellular carcinoma) were observed in patients with incident mutations. CONCLUSION Vaccine escape mutants selected by NA exposure were frequent and steadily increasing during follow-up. Although the high antiviral potency of TDF can mitigate incident mutations, other antiviral options are limited in this respect. The public health implications of their transmission need to be addressed.
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Chen X, He JM, Ding LS, Zhang GQ, Zou XB, Zheng J. Prevalence of hepatitis B virus and hepatitis C virus in patients with human immunodeficiency virus infection in Central China. Arch Virol 2013; 158:1889-94. [PMID: 23553454 DOI: 10.1007/s00705-013-1681-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2012] [Accepted: 02/19/2013] [Indexed: 12/18/2022]
Abstract
Co-infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has an adverse effect on liver disease progression. This study investigated the prevalence of HBV and/or HCV co-infection in HIV-infected patients in Central China. A total of 978 HIV-infected patients from Hunan Province were enrolled. HBV serum markers, anti-hepatitis-C-virus antibody (anti-HCV), HBV DNA, and HBV genotypes were analyzed. The prevalence of hepatitis B surface antigen (HBsAg) and anti-HCV in HIV-infected patients was 19.4 % and 62.4 %, respectively. The prevalence of anti-HCV in HIV-positive intravenous drug users was 93.6 %. Among HBsAg-positive patients, 88.1 % were found to have at least one HBV serum marker. The rates of HIV mono-infection, HBV/HIV dual infection, HCV/HIV dual infection, and HBV/HCV/HIV triple infection were 30.4 %, 7.2 %, 50.2 %, and 12.2 %, respectively. Antibody to HBsAg (Anti-HBs) was more common in anti-HCV-positive than anti-HCV-negative patients (53.3 % vs 40.2 %, P = 0.000), but isolated hepatitis B core antibody (anti-HBc) was more common in anti-HCV-negative than anti-HCV-positive patients (24.2 % vs 12.3 %, P = 0.000). Hepatitis B e antigen (HBeAg) and sexual transmission were independent risk factors for active HBV replication. Intravenous drug use and male sex were independent risk factors, but old age and presence of HBeAg were independent protective factors for anti-HCV. Co-infection of HBV and/or HCV with HIV infection is common in central China. HCV status is associated with anti-HBs and isolated anti-HBc in co-infected patients.
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Affiliation(s)
- Xi Chen
- Hunan Provincial Center for Diseases Control and Prevention, 450 Furongzhong Rd. sec 1, Changsha 410005, China.
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Day SL, Odem-Davis K, Mandaliya KN, Jerome KR, Cook L, Masese LN, Scott J, Kim HN, Graham SM, McClelland RS. Prevalence, clinical and virologic outcomes of hepatitis B virus co-infection in HIV-1 positive Kenyan women on antiretroviral therapy. PLoS One 2013; 8:e59346. [PMID: 23527168 PMCID: PMC3601052 DOI: 10.1371/journal.pone.0059346] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 02/13/2013] [Indexed: 12/17/2022] Open
Abstract
Background Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART. Methods In this prospective cohort study, HIV-1 seropositive women initiated three-drug ART regimens that included lamivudine as the single drug active against HBV. Archived samples were tested for HBsAg, with further testing to determine HBeAg seroprevalence, HBV DNA suppression, and lamivudine resistance. We estimated the prevalence of chronic HBV and examined associations between HBV co-infection and clinical and virologic outcomes with chi-square tests, logistic regression, Kaplan-Meier and Cox regression. Results In a cohort of 159 women followed for a median of 3.4 years (interquartile range 1.4–4.5), 11 (6.9%; 95% CI 3.1–10.7) had chronic HBV infection. Of these, 9 (82%) achieved undetectable plasma HBV DNA levels. One woman developed lamivudine resistance, for an incidence of 3 per 100 person-years. The HBV co-infected women were at greater risk for abnormal ALT elevations compared to HIV-1 mono-infected women (HR 2.37; 95% CI 1.1–5.3). There were no differences between HBV-infected and uninfected women in mortality, CD4 count, or HIV-1 RNA suppression. Conclusion The prevalence of chronic HBV in this cohort was similar to recent studies from other African populations. Given our long-term follow-up, lamivudine resistance was lower than expected for HIV-1/HBV co-infected patients. Improved screening for HBV and extended follow-up of HIV-1/HBV co-infected individuals are needed to better understand the impact of different ART regimens on clinical outcomes in this population.
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Affiliation(s)
- Summer L. Day
- Department of Medicine, University of Washington, Seattle, Washington, United States of America
| | - Katherine Odem-Davis
- Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
- Fred Hutchison Cancer Research Center, Seattle, Washington, United States of America
| | | | - Keith R. Jerome
- Fred Hutchison Cancer Research Center, Seattle, Washington, United States of America
- Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America
| | - Linda Cook
- Fred Hutchison Cancer Research Center, Seattle, Washington, United States of America
- Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America
| | - Linnet N. Masese
- Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
| | - John Scott
- Department of Medicine, University of Washington, Seattle, Washington, United States of America
| | - H. Nina Kim
- Department of Medicine, University of Washington, Seattle, Washington, United States of America
| | - Susan M. Graham
- Department of Medicine, University of Washington, Seattle, Washington, United States of America
- Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya
| | - R. Scott McClelland
- Department of Medicine, University of Washington, Seattle, Washington, United States of America
- Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
- Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya
- Department of Global Health, University of Washington, Seattle, Washington, United States of America
- * E-mail:
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Coffin CS, Osiowy C, Myers RP, Gill MJ. Virology and clinical sequelae of long-term antiviral therapy in a North American cohort of hepatitis B virus (HBV)/human immunodeficiency virus type 1 (HIV-1) co-infected patients. J Clin Virol 2013; 57:103-8. [PMID: 23465393 DOI: 10.1016/j.jcv.2013.02.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Revised: 02/01/2013] [Accepted: 02/05/2013] [Indexed: 02/07/2023]
Abstract
UNLABELLED There are limited recent data worldwide on clinical and virological outcomes in hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfected patients on dual active antiretroviral therapy (ART). METHODS We completed a retrospective review of 53 coinfected patients. HBV DNA in plasma was tested by PCR (sensitivity <20-<55 IU/ml or ∼100-300 copies/ml, Roche Diagnostics). Quantitative hepatitis B surface antigen (qHBsAg) was measured by an in-house assay (calibration range 0.24-62.5 IU/ml). HBV genotyping was done by line probe assay, and HBV variants determined by sequencing the HBV polymerase (P)/overlapping surface (S) gene. RESULTS There were 7% (4/53) non-liver related deaths, ∼11% (6/53) had >F2 fibrosis, including 3 with cirrhosis. The median CD4+ T cell count was 415 cells/mm(3) (range 60-1310). 54% (28/51) were HBeAg-positive, and 81% (43/53) on ART had undetectable HBV DNA but only 5% (3/51) lost HBeAg. In 11/53 with HBV sequencing, 90% (10/11) were found to have HBV genotype A (HBV-A) and/or 27% (3/11) had a mixed A/G infection. Anti-HBV drug resistant mutations were detected in 54% (6/11) (i.e., any combination of rtV173L, rtL180M, M204V) and 45% (5/11) had an immune escape mutation (sP120S). In 12 with qHBsAg testing, the majority (9/12) had low-level qHBsAg ∼1-3 log(10) IU/ml. SUMMARY Liver disease occurs in ∼10% of coinfected patients on ART and many have low-level HBV DNA and qHBsAg. In those sequenced most were HBV-A or mixed A/G genotype, and several carry P and S mutants highlighting the complex molecular virology of HBV during HIV coinfection.
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Affiliation(s)
- C S Coffin
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, 3280 Hospital Drive NW, University of Calgary, Calgary, AB T2N 4Z6, Canada.
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Galluzzo C, Liotta G, Andreotti M, Luhanga R, Jere H, Mancinelli S, Maulidi M, Sagno JB, Pirillo M, Erba F, Amici R, Ceffa S, Marazzi MC, Vella S, Palombi L, Giuliano M. Emergence of lamivudine resistance hepatitis B virus mutations in pregnant women infected with HBV and HIV receiving antiretroviral prophylaxis for the prevention of mother-to-infant transmission in Malawi. J Med Virol 2013; 84:1553-7. [PMID: 22930502 DOI: 10.1002/jmv.23365] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
HIV/HBV co-infection is highly prevalent in sub-Saharan Africa. The aim of this study was to determine if the use of triple combination lamivudine-containing prophylaxis for the prevention of mother-to-infant HIV transmission was associated with the emergence of lamivudine HBV mutations. The study included 21 pregnant co-infected women in Malawi who received either zidovudine or stavudine plus lamivudine and nevirapine from week 25 of gestation until 6 months after delivery or indefinitely if they met the criteria for treatment (CD4+ <350/mm(3)). HBV-DNA was determined using the Roche COBAS assay. Resistance mutations were assessed by the Trugene assay (Siemens Diagnostics). At baseline 33% of the women were HBeAg positive and had HBV-DNA > 10(4) IU/ml. Median CD4 count was 237 cells/mm(3) and median HIV-RNA was 3.8 log(10) copies/ml. After a median of 259 days of treatment, HBV-DNA was detectable in 9 out of 21 patients (42.8%). In three cases the HBV-DNA level was >10(4) IU/ml. Resistance mutations (M204I in five cases and L180M + M204I/V in one case) were present in 6 (28.6%) patients. Women with a resistant virus had significantly higher baseline HBV-DNA levels than those not developing resistance (1.1 × 10(7) IU/ml vs. 20.8 IU/ml, P = 0.022). Levels of ALT and AST were higher in women with resistant viruses compared to those retaining a wild-type virus. A high rate of lamivudine resistance was seen in this cohort of pregnant women. Follow-up of these patients will clarify if the presence of resistance has a significant impact on liver disease.
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Affiliation(s)
- Clementina Galluzzo
- Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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18
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Anggorowati N, Yano Y, Heriyanto DS, Rinonce HT, Utsumi T, Mulya DP, Subronto YW, Hayashi Y. Clinical and virological characteristics of hepatitis B or C virus co-infection with HIV in Indonesian patients. J Med Virol 2012; 84:857-65. [PMID: 22499006 DOI: 10.1002/jmv.23293] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hepatitis virus-related liver disease increases substantially the mortality rate of patients with HIV on highly active antiretroviral therapy (HAART). Therefore, early diagnosis of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important. However, the prevalence of HBV and HCV infection in Indonesian patients infected with HIV is unknown. Therefore, this study examined the molecular and clinical characteristics of HBV and HCV in 126 patients infected with HIV, mostly on HAART, at Dr. Sardjito Hospital, Yogyakarta, Indonesia. The rates of triple infection, HIV/HCV co-infection, HIV/HBV co-infection, and mono-infection were 4.8%, 34.1%, 3.2%, and 57.9%, respectively. Seven HCV genotypes were detected, with genotypes 1a, 1b, 1c, 3a, 3k, 4a, and 6n found in 23 (52%), 1 (2%), 4 (9%), 5 (11%), 7 (16%), 3 (6%), and 1 (2%) patients, respectively, indicating multiple modes of transmission. HBV-DNA was detected in 2/10 patients with hepatitis B surface antigen; both patients were HAART naive. Univariate analysis revealed that male sex, higher education level, injection drug use, sexual contact, alanine aminotransferase ≥40 IU/L, and aspartate aminotransferase-to-platelet ratio index > 0.5 were associated with HCV co-infection. In multivariate analysis, injection drug use (OR: 26.52; 95% CI: 3.52-199.54) and alanine aminotransferase ≥40 IU/L (OR: 6.36; 95% CI: 1.23-32.89) were independently associated with HCV co-infection. HCV co-infection was common among Indonesian patients infected with HIV, particularly among injecting drug users, and was a risk factor for disease progression of HIV.
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Affiliation(s)
- Nungki Anggorowati
- Center for Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe, Japan
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[Consensus document of Gesida and Spanish Secretariat for the National Plan on AIDS (SPNS) regarding combined antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2012)]. Enferm Infecc Microbiol Clin 2012; 30:e1-89. [PMID: 22633764 DOI: 10.1016/j.eimc.2012.03.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Accepted: 03/19/2012] [Indexed: 11/20/2022]
Abstract
This consensus document has been prepared by a panel consisting of members of the AIDS Study Group (Gesida) and the Spanish Secretariat for the National Plan on AIDS (SPNS) after reviewing the efficacy and safety results of clinical trials, cohort and pharmacokinetic studies published in medical journals, or presented in medical scientific meetings. Gesida has prepared an objective and structured method to prioritise combined antiretroviral treatment (cART) in naïve patients. Recommendations strength (A, B, C) and the evidence which supports them (I, II, III) are based on a modification of the Infectious Diseases Society of America criteria. The current antiretroviral treatment (ART) of choice for chronic HIV infection is the combination of three drugs. ART is recommended in patients with symptomatic HIV infection, in pregnancy, in serodiscordant couples with high transmission risk, hepatitis B fulfilling treatment criteria, and HIV nephropathy. Guidelines on ART treatment in patients with concurrent diagnosis of HIV infection and an opportunistic type C infection are included. In asymptomatic patients ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: 1) therapy should be started in patients with CD4 counts <350 cells/μL; 2) when CD4 counts are between 350 and 500 cells/μL, therapy will be recommended and only delayed if patient is reluctant to take it, the CD4 are stabilised, and the plasma viral load is low; 3) therapy could be deferred when CD4 counts are above 500 cells/μL, but should be considered in cases of cirrhosis, chronic hepatitis C, high cardiovascular risk, plasma viral load >10(5) copies/mL, proportion of CD4 cells <14%, and in people aged >55 years. ART should include 2 reverse transcriptase inhibitors nucleoside analogues and a third drug (non-analogue reverse transcriptase inhibitor, ritonavir boosted protease inhibitor or integrase inhibitor). The panel has consensually selected and given priority to using the Gesida score for some drug combinations, some of them co-formulated. The objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining antiviral response. Therapeutic options are limited after ART failures, but an undetectable viral load may be possible nowadays. Adverse events are a fading problem of ART. Guidelines in acute HIV infection, in women, in pregnancy, and to prevent mother-to-child transmission and pre- and post-exposition prophylaxis are commented upon. Management of hepatitis B or C co-infection, other co-morbidities, and the characteristics of ART in HIV-2 infection are included.
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Pourkarim MR, Lemey P, Amini-Bavil-Olyaee S, Houspie L, Verbeeck J, Rahman M, Maes P, Vanwijngaerden E, Nevens F, Van Ranst M. Molecular characterization of hepatitis B virus strains circulating in Belgian patients co-infected with HIV and HBV: overt and occult infection. J Med Virol 2012; 83:1876-84. [PMID: 21915860 DOI: 10.1002/jmv.22174] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) have similar transmission routes, implying that patients infected with HIV are at particular risk for HBV infection. Patients who are co-infected with HIV and HBV progress more rapidly to end-stage liver disease and different HBV genotypes may have a distinct impact on disease progression. One hundred ninety-one anti-HBc-positive sera from Belgian patients co-infected with HIV and HBV were collected during 1998-2008. Full-length HBV genomes as well as large S or partial S genes were amplified and their molecular evolutionary history was analyzed. Clinically, 30 (65.8%) patients were categorized as "overt infection" and 16 (34.7%) cases were categorized as "occult infection." Five distinct HBV genotypes comprising A (69.6%), E (19.6%), followed by D, C, and G were detected. HBV genotype A was observed in all clinical groups and in patients with varying ethnical background. HBV genotype E could be detected in African patients who were mostly infected by heterosexual contacts. Several clinically important mutations at the HBs major hydrophilic region were detected in the new isolates but with no significant difference between occult and overt infection. The high prevalence of HBV genotype A in overt and occult cases, and in particular the detection of certain HBV subgenotypes in patients co-infected with HIV and HBV that carry diagnostic escape mutations, may provide useful information for national guidelines for prophylaxis and treatment.
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Affiliation(s)
- Mahmoud Reza Pourkarim
- Laboratory of Clinical Virology, Rega Institute for Medical Research, Katholieke Universiteit, Leuven, Belgium
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Sheng WH, Hung CC, Chang SY, Liu CJ, Chen MY, Hsieh SM, Kao JH, Chen PJ, Chang SC. Differential clinical and virologic impact of hepatitis B virus genotypes B and C on HIV-coinfected patients receiving lamivudine-containing highly active antiretroviral therapy. Clin Infect Dis 2011; 54:548-55. [PMID: 22156858 DOI: 10.1093/cid/cir851] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The impact of hepatitis B virus (HBV) genotypes B and C on the clinical, immunologic, and virologic outcomes of human immunodeficiency virus (HIV)-infected patients with chronic HBV infection remains largely unknown. METHODS Between January 1997 and December 2008, we enrolled 96 HIV-infected patients with HBV genotype B coinfection and 49 with genotype C coinfection; the patients were followed prospectively until December 2010. Clinical and immunologic outcomes in the context of HBV genotypes as well as the emergence of HBV DNA mutations conferring lamivudine resistance (rtM204I/V) were determined. RESULTS The median duration of lamivudine-containing highly active antiretroviral therapy (HAART) was 2.80 years (interquartile range, 1.73-5.92 years). The 2 groups of HIV-infected patients were comparable in age, sex, baseline HIV profiles, and liver function profiles. Compared with HIV-infected patients with HBV genotype C coinfection, those with genotype B coinfection had a higher risk of hepatitis flares (43.8% vs 26.5%; P = .04), liver disease-related death (9.4% vs 0%; P = .03), hepatitis B e antigen (HBeAg) seroconversion (61.5% vs 25.0%, P = .03), and development of lamivudine resistance (31.3% vs 12.2%; P < .0001). No differences were observed between the 2 groups in terms of the development of hyperbilirubinemia, cirrhosis, or virologic and immunologic responses to HAART. CONCLUSIONS Although therapeutic responses to long-term lamivudine-containing HAART were comparable between HIV-infected patients with HBV genotypes B and C coinfection, patients with genotype B coinfection were more likely to experience acute exacerbations of hepatitis, HBeAg seroconversion, lamivudine resistance, and liver disease-related death than those with genotype C coinfection.
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Affiliation(s)
- Wang-Huei Sheng
- Department of Internal Medicine, Ntional Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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Kouanfack C, Aghokeng AF, Mondain AM, Bourgeois A, Kenfack A, Mpoudi-Ngolé E, Ducos J, Delaporte E, Laurent C. Lamivudine-resistant HBV infection in HIV-positive patients receiving antiretroviral therapy in a public routine clinic in Cameroon. Antivir Ther 2011; 17:321-6. [PMID: 22290198 DOI: 10.3851/imp1911] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND In Africa, most HIV-HBV-coinfected patients on antiretroviral therapy (ART) receive an anti-HBV lamivudine monotherapy that has been shown in northern countries to lead to frequent emergence of drug resistance. We assessed the HBV prevalence and the rate and pattern of lamivudine-resistant HBV mutations in Cameroonian HIV-infected, ART-treated patients. METHODS A cross-sectional survey was performed in 2006-2007 at the HIV/AIDS outpatient clinic of the Central Hospital in Yaoundé, Cameroon. Plasma samples were tested as appropriate for hepatitis B surface antigens, antibodies to hepatitis B core, HBV DNA, genotypes and lamivudine-resistant polymerase mutations. RESULTS Of 552 adult patients (71% women, median age 38 years), 290 had received lamivudine-based ART for 12 months and 262 for 24 months. No patient had received tenofovir. The prevalence of hepatitis B surface antigen was 9.8%. Overall, 26% of seropositive patients had an HBV DNA level >40 IU/ml. Genotypes A and E were identified. Polymerase resistance mutations were detected in 14% and 60% of patients at months 12 and 24, respectively. CONCLUSIONS This study supports both WHO recommendations of screening for HBV before initiation of ART and of using ART containing tenofovir and either lamivudine or emtricitabine in HIV-HBV-coinfected patients in Africa.
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Martin CM, Welge JA, Blackard JT. Hepatitis B virus (HBV) X gene diversity and evidence of recombination in HBV/HIV co-infected persons. J Med Virol 2011; 83:1142-50. [PMID: 21520141 DOI: 10.1002/jmv.22090] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2011] [Indexed: 12/17/2022]
Abstract
The high frequency of mutation during hepatitis B virus (HBV) infection has resulted in 8 genotypes (A-H) with varying effects on disease severity and treatment efficacy. However, analysis of intrapatient HBV diversity is limited, especially during HIV co-infection. Therefore, a preliminary study was performed to analyze HBV X gene diversity in 17 HBV/HIV co-infected individuals. Phylogenetic analysis revealed HBV genotype A in 13 individuals (76.5%) or genotype E in 1 individual (5.9%). Additionally, 3 individuals were dually infected with HBV genotypes A and G (17.6%). Overall, higher genetic distance and entropy were observed in the X region and overlapping polymerase (Pol(X)) regions when compared to the PreS, S, and overlapping polymerase (Pol(PS) and Pol(S)) regions analyzed in the same patients as part of a previous study. In addition, multiple viral variants from 2 individuals with dual HBV infection did not group with either genotype A or G by phylogenetic analysis, indicating possible recombination. SimPlot bootscan analysis confirmed recombination breakpoints within the X gene in both individuals. Recombination between HBV genotypes may represent an important evolutionary strategy that enhances overall pathogenic potential and/or alters the downstream effects of the HBV X protein.
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Affiliation(s)
- Christina M Martin
- Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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Reuter S, Oette M, Wilhelm FC, Beggel B, Kaiser R, Balduin M, Schweitzer F, Verheyen J, Adams O, Lengauer T, Fätkenheuer G, Pfister H, Häussinger D. Prevalence and characteristics of hepatitis B and C virus infections in treatment-naïve HIV-infected patients. Med Microbiol Immunol 2010; 200:39-49. [PMID: 20853118 DOI: 10.1007/s00430-010-0172-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2010] [Indexed: 02/07/2023]
Abstract
In HIV-infected treatment-naïve patients, we analyzed risk factors for either chronic hepatitis B (HBV) infection, occult HBV infection (OHBV) or a positive hepatitis C (HCV) serostatus. A total of 918 patients of the RESINA-cohort in Germany were included in this study. Before initiating antiretroviral therapy, clinical parameters were collected and blood samples were analyzed for antibodies against HIV, HBV and HCV, HBs antigen and viral nucleic acids for HIV and HBV. Present or past HBV infection (i.e. HBsAg and/or anti-HBc) was found in 43.4% of patients. HBsAg was detected in 4.5% (41/918) and HBV DNA in 6.1% (34/554), resulting in OHBV infection in 2.9% (16/554) of patients. OHBV infection could not be ruled out by the presence of anti-HBs (50.1%) or the absence of all HBV seromarkers (25%). A HCV-positive serostatus was associated with the IVDU transmission route, non-African ethnicity, elevated liver parameters (ASL or GGT) and low HIV viral load. Replicative HBV infection and HCV-positive serostatus both correlated with HIV resistance mutations (P = 0.001 and P = 0.028). HBV and HCV infection are frequent co-infections in HIV treatment-naive patients. These co-infections influence viral evolution, clinical parameters and serological markers. Consequently, HIV patients should routinely be tested for HBV and HCV infection before initiating HIV treatment. OHBV infection constituted almost half of all HBV infections with detectable HBV DNA. Due to a lack of risk factors indicating OHBV infection, HBV diagnosis should not only include serological markers but also the detection of HBV DNA.
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Affiliation(s)
- Stefan Reuter
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Moorenstr. 5, 40225 Duesseldorf, Germany.
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Arankalle VA, Gandhe SS, Borkakoty BJ, Walimbe AM, Biswas D, Mahanta J. A novel HBV recombinant (genotype I) similar to Vietnam/Laos in a primitive tribe in eastern India. J Viral Hepat 2010; 17:501-10. [PMID: 20059669 DOI: 10.1111/j.1365-2893.2009.01206.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Genotyping of 20 strains of Hepatitis B virus (HBV) from the Idu Mishmi primitive tribe of northeast India identified multiple genotypes and the presence of a unique cluster grouping with strains from Vietnam and Laos identified as novel recombinants/genotype I. Sequence analysis (similarity and bootscan plots) of three complete HBV genomes from the tribe provided evidence of recombination. Phylogenetic analyses supported recombination between genotypes A, G and C. The Pre-S gene between nt 2943 and 397 was clearly of genotype A origin, whereas nt 397-1397 represented genotype G and nt 1397-2943 represented genotype C. Percentage divergence from genotypes B, D, E, F, G and H varied from 9.2 +/- 0.45% to 13.8 +/- 0.53%, whereas genotype A and C differed by 7.9 +/- 0.42% and 7.4 +/- 0.39% respectively. The identification of similar recombinant viruses in three countries, especially in a primitive tribe with no contact with the outside world suggests that these viruses do not represent recent recombination events, but circulation of closely related viruses highly divergent from known HBV genotypes and should be classified as members of genotype 'I'.
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Affiliation(s)
- V A Arankalle
- Hepatitis Group, National Institute of Virology (Indian Council of Medical Research), Pashan, Pune, Italy.
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[AIDS Study Group/Spanish AIDS Plan consensus document on antiretroviral therapy in adults with human immunodeficiency virus infection (updated January 2010)]. Enferm Infecc Microbiol Clin 2010; 28:362.e1-91. [PMID: 20554079 DOI: 10.1016/j.eimc.2010.03.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2010] [Accepted: 03/14/2010] [Indexed: 12/29/2022]
Abstract
OBJECTIVE This consensus document is an update of antiretroviral therapy recommendations for adult patients with human immunodeficiency virus infection. METHODS To formulate these recommendations a panel made up of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) reviewed the advances in the current understanding of the pathophysiology of human immunodeficiency virus (HIV) infection, the efficacy and safety of clinical trials, and cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend ART was established in each situation. RESULTS Currently, the treatment of choice for chronic HIV infection is the combination of three drugs of two different classes, including 2 nucleosides or nucleotide analogs (NRTI) plus 1 non-nucleoside (NNRTI) or 1 boosted protease inhibitor (PI/r), but other combinations are possible. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: 1) therapy should be started in patients with CD4 counts below 350 cells/microl; 2) When CD4 counts are between 350 and 500 cells/microl, therapy should be started in case of cirrhosis, chronic hepatitis C, high cardiovascular risk, HIV nephropathy, HIV viral load above 100,000 copies/ml, proportion of CD4 cells under 14%, and in people aged over 55; 3) Therapy should be deferred when CD4 are above 500 cells/microl, but could be considered if any of previous considerations concurs. Treatment should be initiated in case of hepatitis B requiring treatment and should be considered for reduce sexual transmission. The objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining antiviral response. Therapeutic options are limited after ART failures but undetectable viral loads maybe possible with the new drugs even in highly drug experienced patients. Genotype studies are useful in these situations. Drug toxicity of ART therapy is losing importance as benefits exceed adverse effects. Criteria for antiretroviral treatment in acute infection, pregnancy and post-exposure prophylaxis are mentioned as well as the management of HIV co-infection with hepatitis B or C. CONCLUSIONS CD4 cells counts, viral load and patient co-morbidities are the most important reference factors to consider when initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the ability to determine viral resistance is leading to a more individualized therapy approach in order to achieve undetectable viral load under any circumstances.
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Hayashi K, Katano Y, Ishigami M, Itoh A, Hirooka Y, Nakano I, Yoshioka K, Yano M, Toyoda H, Kumada T, Goto H. Prevalence and clinical characterization of patients with acute hepatitis B induced by lamivudine-resistant strains. J Gastroenterol Hepatol 2010; 25:745-749. [PMID: 20074155 DOI: 10.1111/j.1440-1746.2009.06118.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Acute hepatitis caused by lamivudine (LMV)-resistant strains has not been reported, and the clinical impact of LMV-resistant strains on acute hepatitis is not known. The aim of this study was to investigate the molecular and clinical characteristics of patients with acute hepatitis B caused by LMV-resistant strains. METHODS Forty-five patients with acute hepatitis B were studied. Hepatitis B virus (HBV) subgenotypes and LMV-resistance mutations were determined by direct sequencing of the preS and polymerase regions, respectively. RESULTS HBV subgenotypes A2 (n = 18), B1 (n = 1), B2 (n = 3), B3 (n = 2), C1 (n = 1), C2 (n = 19) and C6 (n = 1) were detected in patients with acute hepatitis. LMV-resistance mutations were detected in two patients. LMV-resistance mutations (L180M, M204I) were detected in a patient with subgenotype C2 who had acute self-limited hepatitis. The other patient with LMV-resistance mutations (L180M, M204V) was infected with subgenotype A2 and had severe hepatitis. CONCLUSION LMV-resistant strains are rare, but they are starting to be found in patients with acute hepatitis B. Surveillance for detecting drug-resistant HBV strains would be important for clinical practice.
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Affiliation(s)
- Kazuhiko Hayashi
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Wongprasit P, Manosuthi W, Kiertiburanakul S, Sungkanuparph S. Hepatitis B virus drug resistance in HIV-1-infected patients taking lamivudine-containing antiretroviral therapy. AIDS Patient Care STDS 2010; 24:205-9. [PMID: 20377434 DOI: 10.1089/apc.2009.0322] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A cross-sectional study was conducted in HIV-1-infected patients receiving lamivudine-containing antiretroviral therapy (ART) to determine the prevalence and risk factors of hepatitis B virus drug resistance (HBV-DR). HBV DNA and HBV genotypic resistance test were performed. Patients were categorized into two groups: with and without HBV-DR. There were 84 patients with a mean age (standard deviation [SD]) of 42.2 (10.2) years and 77% were males. Median (range) duration of ART and lamivudine use was 46 (3-177) and 40 (3-140) months, respectively. Median (range) CD4 cell count was 352 (49-790) cells/mm(3). Of all, 19 (23%) had HBV-DR with a median (range) HBV DNA of 2.56 x 10(7) (2.54 x 10(3)-11 x 10(7)) IU/mL. In univariate analysis, there were no differences in age, gender, ART regimen, liver function test, anti-HBc antibody, anti-HCV antibody between the two groups. Patients with HBV-DR had a higher proportion of positive HBeAg (68.4% versus 3.8%, p < 0.001). In multivariate analysis, positive HBeAg (odds ratio [OR) 16.64; 95% confidence interval [CI], 3.31-83.60] and duration of lamivudine use [per 6-month increment, OR 1.24; 95% CI, 1.06-1.36] were significant risk factors for HBV-DR. All 19 patients with HBV-DR had lamivudine resistance with the mutations as follows: M204V/I (95%), L180M/A181T (95%), L80V/I (47%), V173L (32%), and N236T (21%). Of these, 95%, 84%, 84%, and 0% of patients had HBV-DR to telbivudine, entecavir, adefovir, and tenofovir, respectively. HBV-DR is common in HBV/HIV-1 coinfected patients receiving lamivudine-containing ART without tenofovir. Positive HBeAg and longer duration of lamivudine use are risk factors for HBV-DR. In addition to lamivudine resistance, cross-resistance to other anti-HBV drugs is also frequently observed.
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Affiliation(s)
- Pawinee Wongprasit
- Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Weerawat Manosuthi
- Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand
| | - Sasisopin Kiertiburanakul
- Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Somnuek Sungkanuparph
- Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Soriano V, Mocroft A, Peters L, Rockstroh J, Antunes F, Kirkby N, de Wit S, Monforte AD, Flisiak R, Lundgren J, on behalf of EuroSIDA. Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe. J Antimicrob Chemother 2010; 65:548-555. [DOI: 10.1093/jac/dkp479] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Abstract
Hepatitis B virus (HBV) is one of the most widely distributed viruses that infect humankind. Distinct clinical and virological characteristics of the HBV-infection have been reported in different geographical parts of the world and are increasingly associated with genetic diversity of the infecting virus. HBV is classified into genotypes and subgenotypes that are associated with ethnicity and geography. The genetic diversity of HBV in its various aspects has been the subject of extensive investigations during the last few decades. Since molecular epidemiology research tools have become widely available, the number of new publications in this field has grown exponentially. This review summarises the recent publications on the geographical distribution of genetic variants of HBV, and proposes updated criteria for the identification of new genotypes and subgenotypes of the virus.
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Affiliation(s)
- Fuat Kurbanov
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya
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Cassino L, Laufer N, Salomon H, Campos R, Quarleri J. Hepatitis B precore/core promoter mutations in isolates from HBV-monoinfected and HBV-HIV coinfected patients: a 3-yr prospective study. J Clin Virol 2009; 46:354-359. [PMID: 19800842 DOI: 10.1016/j.jcv.2009.09.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2009] [Accepted: 09/09/2009] [Indexed: 01/12/2023]
Abstract
BACKGROUND The course of chronic HBV infection is modified by HIV-coexistence. OBJECTIVE To analyze the role of HBV genomic heterogeneity in basal core promoter (BCP) and precore (Pc) genomic regions. STUDY DESIGN In a 3-yr prospective study, 39 HBV infected patients (20 monoinfected and 19 HIV-coinfected) were included. Eighty-two HBV isolates were studied at quasispecies level in the BCP/Pc genomic region. Clinical records obtained include data on lamivudine therapy and resistance mutations, HBV and HIV-viral load. RESULTS HBV isolates were predominantly ascribed to genotype (Gt) A2 among HBV-monoinfected and HIV-coinfected patients. BCP mutations in isolates from monoinfected patients were significantly more frequent than in those from coinfected ones, irrespective of the HBe expression pattern (p<0.0001). Regardless of the HIV-coexistence, the Pc mutation at G1896A only barely appeared among clone-derived sequences of GtF1 isolates, mainly from HBe(-) HBV-monoinfected patients. CONCLUSIONS HBV isolates characterized from HIV-coinfected patients seem to be more prone to exhibit a wild type genomic pattern at BCP regulatory region with respect to those from HBV-monoinfected ones. Besides, mutations at Pc region might be genotype-dependent in their frequency but not on HIV co-presence related.
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Affiliation(s)
- Lucila Cassino
- Centro Nacional de Referencia para el SIDA, Dto. Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina
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Soriano V, Vispo E, Labarga P, Medrano J, Barreiro P. Viral hepatitis and HIV co-infection. Antiviral Res 2009; 85:303-15. [PMID: 19887087 DOI: 10.1016/j.antiviral.2009.10.021] [Citation(s) in RCA: 147] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2009] [Revised: 10/20/2009] [Accepted: 10/23/2009] [Indexed: 12/13/2022]
Abstract
Chronic hepatitis B virus (HBV) infection is overall recognised in 10% of HIV+ persons worldwide, with large differences according to geographical region. Chronic hepatitis C virus (HCV) infection affects 25% of HIV+ individuals, with greater rates ( approximately 75%) in intravenous drug users and persons infected through contaminated blood or blood products. HIV-hepatitis co-infected individuals show an accelerated course of liver disease, with faster progression to cirrhosis. The number of anti-HBV drugs has increased in the last few years, and some agents (e.g. lamivudine, emtricitabine, tenofovir) also exert significant activity against HIV. Emergence of drug resistance challenges the long-term benefit of anti-HBV monotherapy, mainly with lamivudine. The results using new more potent anti-HBV drugs (e.g. tenofovir) are very promising, with prospects for stopping or even revert HBV-related liver damage in most cases. With respect to chronic hepatitis C, the combination of pegylated interferon plus ribavirin given for 1 year permits to achieve sustained HCV clearance in no more than 40% of HIV-HCV co-infected patients. Thus, new direct anti-HCV drugs are eagerly awaited for this population. Although being a minority, HIV+ patients with delta hepatitis and those with multiple hepatitis show the worst prognosis. Appropriate diagnosis and monitoring of chronic viral hepatitis, including the use of non-invasive tools for assessing liver fibrosis and measurement of viral load, may allow to confront adequately chronic viral hepatitis in HIV+ patients, preventing the development of end-stage liver disease, for which the only option available is liver transplantation. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.
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Affiliation(s)
- Vincent Soriano
- Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
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Iacomi F, Vincenti D, Vairo F, Solmone M, Mariano A, Piselli P, Puro V, Capobianchi MR, Antonucci G. Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B. J Med Virol 2009; 81:1151-6. [PMID: 19475624 DOI: 10.1002/jmv.21505] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125-213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L + rtL180M + rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0-61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5-34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat.
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Affiliation(s)
- Fabio Iacomi
- Clinical Department of Infectious Diseases, National Institute for Infectious Disease, L. Spallanzani, Rome, Italy
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Svicher V, Gori C, Trignetti M, Visca M, Micheli V, Bernassola M, Salpini R, Gubertini G, Longo R, Niero F, Ceccherini-Silberstein F, De Sanctis GM, Spanò A, Cappiello G, Perno CF. The profile of mutational clusters associated with lamivudine resistance can be constrained by HBV genotypes. J Hepatol 2009; 50:461-70. [PMID: 19041149 DOI: 10.1016/j.jhep.2008.07.038] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2008] [Revised: 07/28/2008] [Accepted: 07/28/2008] [Indexed: 01/12/2023]
Abstract
BACKGROUND/AIMS To investigate the different clusters of mutations associated with lamivudine resistance in HBV genotypes D and A. METHODS HBV reverse transcriptase sequences of 89 HBV-infected patients failing lamivudine treatment were analyzed. The association of mutations with HBV genotypes was assessed by Chi-Squared test and multivariate logistic regression analysis. Covariate analysis was based on hierarchical clustering. RESULTS In genotype A, the rtM204V (prevalence: 68.2%) was the main sign of lamivudine failure. Multivariate analysis confirmed that genotype A is the only predictor for rtM204V emergence (OR: 14.5 [95% CI: 1.3-158], P=0.02). Covariate analysis showed that rtM204V clusters with rtL180M, rtL229V (corresponding to sF220L in the HBsAg), and, interestingly, with HBsAg mutation sS207N (bootstrap=0.95). Both sF220L and sS207N co-localized in the fourth transmembrane HBsAg domain. In contrast, in genotype D the primary mutations rtM204V and rtM204I occurred with similar prevalence (39.1% versus 45.3%, P=0.47), and showed a distinct pattern of compensatory mutations. rtM204V clusters with mutations localized in the RT-B domain (rtV173L, rtL180M, and rtT184A/S) (bootstrap=0.94), while rtM204I clusters with mutations localized in the RT-A domain (rtS53N, rtT54Y, and rtL80I/V) (bootstrap=0.96) (without associations with HBsAg specific mutations). CONCLUSIONS HBV genotype plays an important role in driving RT evolution under lamivudine treatment, and thus can be relevant for therapeutic sequencing, immunological response and disease progression.
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Affiliation(s)
- Valentina Svicher
- Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
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Marugán RB, Garzón SG. DNA-guided hepatitis B treatment, viral load is essential, but not sufficient. World J Gastroenterol 2009; 15:423-30. [PMID: 19152446 PMCID: PMC2653363 DOI: 10.3748/wjg.15.423] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2008] [Revised: 12/17/2008] [Accepted: 12/24/2008] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B (CHB) are at increased risk of developing liver cirrhosis, hepatic de-compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CHB who are hepatitis B e antigen (HBeAg)-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAg-negative CHB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CHB.
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Soriano V, Rivas P, Nuñez M. Editorial Commentary:Risks and Benefits of Using Antiretroviral Therapy in HIV‐Infected Patients with Chronic Hepatitis B in Developing Regions. Clin Infect Dis 2008; 47:1486-9. [DOI: 10.1086/593105] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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Trinks J, Cuestas ML, Tanaka Y, Mathet VL, Minassian ML, Rivero CW, Benetucci JA, Gímenez ED, Segura M, Bobillo MC, Corach D, Ghiringhelli PD, Sánchez DO, Avila MM, Peralta LAM, Kurbanov F, Weissenbacher MC, Simmonds P, Mizokami M, Oubiña JR. Two simultaneous hepatitis B virus epidemics among injecting drug users and men who have sex with men in Buenos Aires, Argentina: characterization of the first D/A recombinant from the American continent. J Viral Hepat 2008; 15:827-838. [PMID: 18507755 DOI: 10.1111/j.1365-2893.2008.00997.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Previous studies have revealed that hepatitis B virus (HBV)/D and HBV/F predominate among blood donors from Buenos Aires, Argentina. In the present study, blood samples from two high-risk groups were analysed: 160 corresponding to street- and hospital-recruited injecting drug users [81.2% showing the 'anti-hepatitis B core antigen (anti-HBc) only' serological pattern] and 20 to hepatitis B surface antigen (HBsAg)(+)/anti-HBc(+) men who have sex with men. HBV genotypes were assigned by polymerase chain reaction amplification followed by restriction fragment length polymorphism and confirmed by nucleotide sequencing of two different coding regions. HBV DNA was detected in 27 injecting drug users (16.9%, occult infection prevalence: 7.7%), and 14 men who have sex with men (70%). HBV/A prevailed among injecting drug users (81.8%) while HBV/F was predominant among men who have sex with men (57.1%). The high predominance of HBV/A among injecting drug users is in sharp contrast to its low prevalence among blood donors (P = 0.0006) and men who have sex with men (P = 0.0137). Interestingly, all HBV/A S gene sequences obtained from street-recruited injecting drug users encoded the rare serotype ayw1 and failed to cluster within any of the known A subgenotypes. Moreover, one of the HBV strains from a hospital-recruited injecting drug user was fully sequenced and found to be the first completely characterized D/A recombinant genome from the American continent. Data suggest that two simultaneous and independent HBV epidemics took place in Buenos Aires: one spreading among injecting drug users and another one sexually transmitted among the homosexual and heterosexual population.
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Affiliation(s)
- J Trinks
- Centro para el Estudio de Hepatitis Virales, Depto. de Microbiología, Fac. de Medicina, Universidad de Buenos Aires (UBA), Buenos Acres, Argentina
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Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. AIDS 2008; 22:1399-410. [PMID: 18614862 DOI: 10.1097/qad.0b013e3282f8b46f] [Citation(s) in RCA: 113] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nearly 10% of the estimated 36 million people having HIV worldwide suffer from chronic hepatitis B virus (HBV) infection. The advent of new antiviral agents against HBV and the recent availability of improved molecular diagnostic tools have revolutioned the management of HIV/HBV coinfected patients. The present study represents an update of the current knowledge about HBV/HIV coinfection and an intent to provide practical advise about how to give the best care to HIV-infected persons with chronic hepatitis B.
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Management of hepatitis B virus co-infection on and off antiretroviral therapy. Curr HIV/AIDS Rep 2008; 5:86-93. [DOI: 10.1007/s11904-008-0014-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Lessells RJ, Main J, Cooke GS. HIV and hepatitis B co-infection in Africa. THE LANCET. INFECTIOUS DISEASES 2008; 8:210-1. [DOI: 10.1016/s1473-3099(08)70047-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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The implications of antiviral drugs with activity against hepatitis B virus and HIV. Curr Opin Infect Dis 2008; 20:621-8. [PMID: 17975413 DOI: 10.1097/qco.0b013e3282f1e022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE OF REVIEW Around 10% of individuals infected with HIV suffer from chronic hepatitis B virus infection. This represents at least 4 million people worldwide. HIV infection modifies the course of hepatitis B virus associated liver disease with faster progression to cirrhosis. The number of anti-hepatitis B virus drugs has increased within the last few years, and some of them also exert activity against HIV-1. The aim of this article is to update the current knowledge on antiviral therapy for chronic hepatitis B in HIV-infected patients. RECENT FINDINGS In the absence of successful anti-hepatitis B virus therapy, morbidity and mortality associated with liver disease are increased in hepatitis B virus/HIV coinfected individuals. Data derived from studies using new more potent anti-hepatitis B virus drugs are very promising, and strategies to use these antivirals sequentially and/or in combination are being developed. Hopefully, this success will help bring a halt to liver-related complications and death in the hepatitis B virus/HIV coinfected population. SUMMARY Appropriate diagnosis and monitoring of chronic hepatitis B, including the use of noninvasive tools for assessing liver fibrosis, measurement of serum hepatitis B virus-DNA, and drug resistance testing, along with wise use of antivirals may convert hepatitis B virus/HIV coinfection into a manageable disease.
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