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Impact of Lamivudine-Based Antiretroviral Treatment on Hepatitis B Viremia in HIV-Coinfected South Africans.

ABSTRACT: This prospective study investigated the impact of lamivudine-containing antiretroviral therapy (ART) on HIV-positive patients in South Africa with baseline hepatitis B virus (HBV) infection. Follow-up samples from 56 HBV/HIV co-infected patients, 25 with occult HBV infection (OBI) and 31 with chronic HBV infection (CHB), were available for analysis. HBV viral loads were quantified at 6, 12, 18, and 24 months post-ART initiation by the COBAS TaqMan HBV Test 48 assay, and the HBV polymerase gene was amplified with an in-house nested polymerase chain reaction assay. During 24 months of lamivudine-based ART, 6 of 8 (75%) OBI and 4 of 6 (67%) CHB patients achieved undetectable levels of HBV DNA, while 2 patients had persistent HBV DNA levels ? 2 × 105 despite lamivudine-based ART for 24 months. HIV viremia was undetectable in all patients at 12 months, suggesting high adherence to ART. Several lamivudine-associated HBV resistance mutations, including L180M, A181T, M204I, and M204V, were observed. Sequence analysis also revealed a rare genotype G infection. While resource-limited settings may use lamivudine-based ART because of availability and low cost, antivirals with dual therapy against HBV and HIV (e.g., lamivudine and tenofovir) should always be recommended with the regular monitoring of HBV viremia levels.

SUBMITTER: Lukhwareni A

PROVIDER: S-EPMC7354521 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Impact of Lamivudine-Based Antiretroviral Treatment on Hepatitis B Viremia in HIV-Coinfected South Africans.

Lukhwareni Azwidowi A Gededzha Maemu Petronella MP Amponsah-Dacosta Edina E Blackard Jason T JT Burnett Rosemary J RJ Selabe Selokela Gloria SG Kyaw Thanda T Mphahlele M Jeffrey MJ

Viruses 20200611 6

This prospective study investigated the impact of lamivudine-containing antiretroviral therapy (ART) on HIV-positive patients in South Africa with baseline hepatitis B virus (HBV) infection. Follow-up samples from 56 HBV/HIV co-infected patients, 25 with occult HBV infection (OBI) and 31 with chronic HBV infection (CHB), were available for analysis. HBV viral loads were quantified at 6, 12, 18, and 24 months post-ART initiation by the COBAS TaqMan HBV Test 48 assay, and the HBV polymerase gene w ...[more]

PMID: 32545313

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Project description:BACKGROUND: Lamivudine inhibits replication of both human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and is commonly used as part of antiretroviral therapy. The main limitation in the use of lamivudine is resistant mutation selection. Most of these mutations affect the YMDD motif of the HBV DNA polymerase. The resistance occurs through M550V or M550I aminoacid replacements. The M550V variation may be accompanied by L526M mutation, notably in HIV-HBV co-infected patients. The aim of this study was to investigate mutations associated with lamivudine resistance in a hemodialysis patient chronically co-infected with HIV-1 and HBV, who was submitted to several antiretroviral treatments. METHODS: HBV isolates derived from three blood samples collected at different times of antiretroviral therapies with and without lamivudine, were titred and submitted to nucleotide sequencing. RESULTS: HBV isolate derived from a sample collected in 1999 during an antiretroviral treatment with lamivudine showed the lamivudine resistant double mutation (L526M, M550V). However, no mutation associated with lamivudine resistance was observed in the HBV genome derived from the sample collected during a period of treatment without lamivudine (2001). After reinstitution of lamivudine (2002), the predominant HBV population exhibited a rare triple mutation (V519L, L526M, M550V), which has previously been associated with an in vitro reduction of virus antigenicity (escape mutant). HBV DNA was detected at high levels (108-109 copies/ml) in the three blood samples. CONCLUSIONS: Reintroduction of lamivudine as part of antiretroviral treatment in a patient who had developed lamivudine resistant HBV strains favored the predominance of an HBV isolate with reduced antigenicity. The absence of hepatitis acute exacerbation in this patient may be correlated to the absence of significant variations of the viral load, which was independent of the presence of mutations in the HBV DNA polymerase.

Dataset Information

Impact of Lamivudine-Based Antiretroviral Treatment on Hepatitis B Viremia in HIV-Coinfected South Africans.

Publications

Impact of Lamivudine-Based Antiretroviral Treatment on Hepatitis B Viremia in HIV-Coinfected South Africans.

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