Dataset Information

Hepatitis B Virus (HBV) Infection and Re-activation During Nucleos(t)ide Reverse Transcriptase Inhibitor-Sparing Antiretroviral Therapy in a High-HBV Endemicity Setting.

ABSTRACT:

Background

We monitored the evolution of markers of hepatitis B virus (HBV) infection in virologically suppressed HIV-positive patients switching to nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapy within a randomized trial in Cameroon.

Methods

HBV surface antigen (HBsAg), HBV DNA, and antibodies against surface (anti-HBs), core (total anti-HBc), and e-antigen (anti-HBe) were measured retrospectively in samples collected at study entry and over 48 weeks after NRTI discontinuation.

Results

Participants (n = 80, 75% females) had a plasma HIV-1 RNA <60 copies/mL, a median CD4 count of 466 cells/mm³, and undetectable HBsAg and HBV DNA at study entry. After NRTI discontinuation, 3/20 (15.0%) anti-HBc-negative patients showed evidence indicative or suggestive of incident HBV infection (163 cases/1000 person-years); 6/60 (10.0%) anti-HBc-positive patients showed evidence indicative or suggestive of HBV reactivation (109 cases/1000 person-years). In one case of reactivation, anti-HBs increased from 14 to >1000 IU/L; sequencing showed HBV genotype A3 and 3 escape mutations in surface (Y100C, K122R, Y161FY). Alongside new-onset detection of HBsAg or HBV DNA, 1 patient experienced acute hepatitis and 6 patients experienced mild or marginal increases in serum transaminase levels.

Conclusions

Evolving treatment strategies for sub-Saharan Africa must be accompanied by the formulation and implementation of policy to guide appropriate assessment and management of HBV status.

SUBMITTER: Abdullahi A

PROVIDER: S-EPMC6201150 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Hepatitis B Virus (HBV) Infection and Re-activation During Nucleos(t)ide Reverse Transcriptase Inhibitor-Sparing Antiretroviral Therapy in a High-HBV Endemicity Setting.

Abdullahi Adam A Fopoussi Olga Mafotsing OM Torimiro Judith J Atkins Mark M Kouanfack Charles C Geretti Anna Maria AM

Open forum infectious diseases 20181005 10

<h4>Background</h4>We monitored the evolution of markers of hepatitis B virus (HBV) infection in virologically suppressed HIV-positive patients switching to nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapy within a randomized trial in Cameroon.<h4>Methods</h4><b><i> </i></b> HBV surface antigen (HBsAg), HBV DNA, and antibodies against surface (anti-HBs), core (total anti-HBc), and e-antigen (anti-HBe) were measured retrospectively in samples collected at study ent ...[more]

PMID: 30377627

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Project description:Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS "95-95-95" target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)-M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)-K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTI-based antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana.

Project description:AbstractCo-infection of Hepatitis B (HBV) and Delta viruses (HDV) represent the most severe form of viral hepatitis. While treatment with pegylated Interferon alpha (PEG-IFNα) is well established, therapy with nucleoside or nucleotide analogues (NA) has been a matter of debate. We aimed to investigate the role of NA treatment in a well-defined single centre cohort.In a retrospective approach, we observed 53 HDV RNA positive and/or anti-HDV-positive patients recruited at a German referral centre between 2000 and 2019. Patients were followed for at least 3 months (mean time of follow up: 4.6 years; range: 0.2-14.1 years). Patients who had liver transplantation or hepatocellular carcinoma at the time of presentation were excluded. 43% (n = 23) were treated with NA, 43% (n = 23) received IFNα-based therapies and 13% (n = 7) were untreated.Liver cirrhosis was already present in 53% (28/53) of patients at first presentation. During follow-up, liver-related endpoints developed in 44% of all patients (n = 23). NA-treatment was associated with a significantly worse clinical outcome (P = .01; odds ratio [OR] = 4.92; CI = 1.51-16.01) compared to both, untreated (P = .38; OR = 0.46; CI = 0.80-2.61) and IFNα-based-treated patients (P = .04; OR = 0.29; CI = 0.89-0.94) in univariate logistic regression analysis. HBsAg levels declined by more than 50% during NA-based therapy in only 7 cases (7/23; mean time: 3.6 years; range: 0.8-8.5 years) and during IFNα-based therapy in 14 cases (14/23; mean time: 2.8 years, range 0.7-8.5 years). HDV RNA became undetectable during follow up in 30% of patients receiving NA alone (7/23; mean time: 5.0 years; range: 0.6-13.5 years), in 35% of patients receiving IFNα-based therapy (8/23; mean time: 2.9 years, range: 0.3-7.6 years).The effect of NA in patients with HBV/HDV co-infection is limited. Treatment with NA was associated with a higher likelihood of clinical disease progression. Interferon alpha therapy was beneficial in reducing liver complications and improves long-term outcome.

Dataset Information

Hepatitis B Virus (HBV) Infection and Re-activation During Nucleos(t)ide Reverse Transcriptase Inhibitor-Sparing Antiretroviral Therapy in a High-HBV Endemicity Setting.

Background

Methods

Results

Conclusions

Publications

Hepatitis B Virus (HBV) Infection and Re-activation During Nucleos(t)ide Reverse Transcriptase Inhibitor-Sparing Antiretroviral Therapy in a High-HBV Endemicity Setting.

Similar Datasets

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