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

• Published in: Clinical infectious diseases Vol. 59; no. 11; pp. 1618 - 1626
• Main Authors: Aoudjane, Samir, Chaponda, Mas, del Castillo, Antonio Adrián González, O'Connor, Jemma, Noguera, Marc, Beloukas, Apostolos, Hopkins, Mark, Khoo, Saye, van Oosterhout, Joep J., Geretti, Anna Maria
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.2014
• Series: Editor's choice
• Subjects: Adult; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretrovirals; Antiviral agents; Biological and medical sciences; DNA sequence analysis; DNA, Viral - genetics; Drug resistance; Drug Resistance, Viral; Female; Genomes; Genotype & phenotype; Hepatitis; Hepatitis antigens; Hepatitis B; Hepatitis B - drug therapy; Hepatitis B - virology; Hepatitis B virus; Hepatitis B virus - classification; Hepatitis B virus - genetics; Hepatitis B virus - physiology; High throughput nucleotide sequencing; HIV; HIV 1; HIV infections; HIV Infections - drug therapy; HIV Infections - virology; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Lamivudine - adverse effects; Lamivudine - therapeutic use; Malawi; Male; Medical sciences; Nevirapine - adverse effects; Nevirapine - therapeutic use; Pharmacology. Drug treatments; Phylogeny; Retrospective Studies; Sequence Analysis, DNA; Stavudine - adverse effects; Stavudine - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral hepatitis; Viral Load - drug effects; Virus Replication - drug effects; Viruses; Malawi; Africa; Human; Immunopathology; Antiretroviral agent; Treatment resistance; Typing; Orthohepadnavirus; Hepatic disease; Genotype; AIDS; Immune deficiency; Epidemiology; Infection; Virus; Viral hepatitis B; Chemotherapy; Microbiological investigation; Treatment; Hepadnaviridae; Viral disease; Digestive diseases; Adult; Antiviral; Replication; Hepatitis B virus; viral load; sub-genotype A1; resistance; Africa; lamivudine
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciu630

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.