High Incidence of Lamivudine-Resistance-Associated Vaccine-Escape HBV Mutants among HIV-Coinfected Patients on Prolonged Antiretroviral Therapy

Pal, Ananya; Sarkar, Neelakshi; Saha, Debraj; Guha, Subhashish Kamal; Saha, Bibhuti; Chakrabarti, Sekhar; Chakravarty, Runu

doi:10.3851/imp2942

Cited by 18 publications

(19 citation statements)

References 40 publications

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“…This serum marker of active viral replication was accompanied by high serum levels of HBV DNA [22, 40]. We found a similar phenomenon by univariate analysis in our study.…”

Section: Discussionsupporting

confidence: 78%

“…However, this could not be confirmed by multivariate analysis. The median of CD4+ lymphocyte counts was found to be significantly higher in patients with 3TC-resistant mutations than viraemic HBV patients without these mutations [22]. We also obtained similar results by univariate analysis in our study, although again this could not be confirmed on multivariate analysis.…”

Section: Discussionsupporting

confidence: 74%

“…The dominant pattern of resistance (71.4%) among treatment-experienced patients with mutated strains (rtM204V + rtL180M) was higher than that in the European multicenter study (29%) [34] and Ghana (47.6%) [23]. The rtV173LtrtL180MtrtM204V triple change has already been described in patients with HIV and HBV co-infection [35], and resulted in codon changes in the surface open reading frame (ORF; sE164D and sI195M, respectively) [22, 24]. In our study, the triple mutations caused one more codon change in the surface ORF (sW196L) in 2 patients.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of HBV drug-resistant mutations in this special population varies with the antiviral agents and the duration of exposure to the drugs [21]. The prevalence in 3TC monotreatment is about 40–77.8% among those who receive 3TC treatment for 1 year or longer [22, 23]. 3TC resistance may occur in a small proportion of patients during 3TC plus TDF treatment [24, 25].…”

Section: Discussionmentioning

confidence: 99%

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High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

Jia

Chen

et al. 2018

Intervirology

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Objectives: We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China. Methods: Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed. Results: The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3–96.7) was significantly higher than that in group 1 (1.4%, 95% CI –1.4 to 4.2; χ² = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 10⁶ copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations. Conclusion: Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.

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“…This serum marker of active viral replication was accompanied by high serum levels of HBV DNA [22, 40]. We found a similar phenomenon by univariate analysis in our study.…”

Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

Jia

Chen

et al. 2018

Intervirology

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“…Three major patterns of mutations in the HBV polymerase associated with lamivudine resistance were described in HBV/HIV co-infected patients receiving ART with lamivudine as the sole-anti-HBV drug: single rtM204V, double rtL180M+rtM204V and triple rtV173L+rtL180M+rtM204V. This triple mutant is related to a vaccine escape mutant due to the corresponding change in the overlapped S-ORF [61]. Thus, the use of lamivudine as the only active anti-HBV agent is discouraged [62].…”

Section: Current Prevalence Of S-escape Mutantsmentioning

confidence: 99%

Hepatitis B Virus (HBV) and S-Escape Mutants: From the Beginning until Now

Maria¹

2015

JHVRV

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Despite of the progress made in vaccine and antiviral therapy development, hepatitis B virus (HBV) infection remains a major health care problem. More than 240 million people are chronically infected worldwide showing differences in the severity of liver disease, clinical outcome and response to immune-and antiviraltherapy. Parameters associated with the host immune system (HBV specific Tand/or B-cell repertoires, defective antigen presentation and diminished Th1/ Th2 response ratio) and viral factors such as the HBV genotypes and their evolving variants/mutants, have largely contributed to explaining such differences. The unique genomic structure and replication cycle of HBV provide much opportunity for mutations to occur in any of its genes undergoing selection pressures, such as those associated with the host immune system, the hepatitis B vaccine and/ or hepatitis B immune globulin and the antiviral therapy with nucleos(t)ide analogues. Firstly, this review describes the current prevalence of S-escape mutants worldwide. Secondly, the clinical implications of such surface gene variants and the impact of universal hepatitis B vaccination on HBV mutations and genotypes are discussed. Finally, the fact that the immune escape process also extends well beyond HBV is addressed.

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Emerging Challenges in Managing Hepatitis B in HIV Patients

et al. 2015

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Roughly 10 % of HIV-positive individuals worldwide have concomitant chronic hepatitis B virus (HBV) infection, with large differences between geographical regions and/or risk groups. Hepatitis B is a preventable infection with vaccines. However, it cannot be eradicated once acquired, resembling HIV and in contrast with HCV. In developed countries, hepatitis B exhibits particular features in the HIV population. First, HBV infection is less frequently misdiagnosed than in the general population. Second, nucleos(t)ide analogs active against HBV are widely used as part of antiretroviral combinations and are taken by most HIV patients. Lastly, as the HIV population ages given the success of antiretroviral therapy, non-AIDS co-morbidities are becoming a major cause of disease, for which specific drugs are required, increasing the risk of interactions and hepatotoxicity. Furthermore, concern on HBV reactivation is rising as immunosuppressive drug therapies are increasingly been used for cancers and other non-malignant conditions. In this scenario, new challenges are emerging in the management of hepatitis B in HIV-positive individuals. Among them, major interest is focused on failures to suppress HBV replication, HBV breakthroughs and reactivations, the meaning of isolated anti-HBc, screening for liver cancer, and the complexity arising when hepatitis viruses C and/or D are additionally present. This review will focus on these challenges and the major advances in HBV coinfection in HIV.

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High Incidence of Lamivudine-Resistance-Associated Vaccine-Escape HBV Mutants among HIV-Coinfected Patients on Prolonged Antiretroviral Therapy

Abstract: 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.

Cited by 18 publications

References 40 publications

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China

Hepatitis B Virus (HBV) and S-Escape Mutants: From the Beginning until Now

Emerging Challenges in Managing Hepatitis B in HIV Patients

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