Long-term hepatitis B virus (HBV) response to lamivudine-containing highly active antiretroviral therapy in HIV-HBV co-infected patients in Thailand

PLoS One. 2012;7(7):e42184. doi: 10.1371/journal.pone.0042184. Epub 2012 Jul 31.

Abstract

Background: Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known.

Methodology/principal finding: HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log(10) IU/mL and 4.47 log(10) copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L.

Conclusions: All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes
  • Drug Resistance, Viral / genetics
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Hepatitis B / complications
  • Hepatitis B / drug therapy*
  • Hepatitis B virus / physiology
  • Humans
  • Lamivudine / pharmacology
  • Lamivudine / therapeutic use*
  • Male
  • Mutation
  • Thailand
  • Viral Load
  • Virus Replication / drug effects

Substances

  • Lamivudine
  • Alanine Transaminase

Associated data

  • ClinicalTrials.gov/NCT00433030

Grants and funding

This work was supported by Agence Nationale de Recherches sur le Sida et les hépatites virales (grant number ANRS 12-179); the Global Fund to fight AIDS, TB and Malaria; the Institut de Recherche pour le Développement (IRD), France; and Thailand International Development Cooperation Agency (TICA), Thai Ministry of Foreign Affairs. WK received scholarships from the IRD, the Franco-Thai cooperation program in Higher Education and Research, the Faculty of Associated Medical Sciences, Chiang Mai University, and the French Ministry of Foreign Affairs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.