Impact of lamivudine on HIV and hepatitis B virus-related outcomes in HIV/hepatitis B virus individuals in a randomized clinical trial of antiretroviral therapy in southern Africa

AIDS. 2011 Sep 10;25(14):1727-35. doi: 10.1097/QAD.0b013e328349bbf3.

Abstract

Objective: To examine HIV and hepatitis B virus (HBV)-related outcomes in HIV/HBV-coinfected participants in the PHIDISA II study by use of HBV-active vs. non-HBV-active antiretroviral therapy (ART).

Design and methods: PHIDISA II was a randomized study of ART therapy in HIV-infected adults employing zidovudine along with didanosine, or lamivudine along with stavudine in a factorial 2x2 design. HIV/HBV-coinfected participants by randomization received HBV-active or non-HBV-active ART. The following outcomes of interest were examined: immunological recovery and HIV RNA suppression; hepatic flare; HBV DNA suppression; and mortality.

Results: HIV/HBV coinfection was present in 106 of 1771 (6%) of participants. Participants with HIV/HBV coinfection were more likely to be men, and have higher baseline alanine aminotransferase, lower albumin, and lower platelets than those with HIV monoinfection. Median CD4 cell gain and HIV RNA suppression was similar across all groups. Hepatic flare was observed in 9.4% of coinfected and 0.02% monoinfected participants. HBV DNA suppression (<55 IU/ml) at week 48 was observed in only 33% of those on lamivudine vs. 13% in those on no HBV-active drugs (P = 0.13). Mortality over follow-up was significantly greater in coinfected (17%) than monoinfected (11%) participants (P = 0.04).

Conclusion: In summary, the use of lamivudine-containing ART in HIV/HBV participants in PHIDISA II resulted in little additional benefit over that of ART itself and failed to impact on the greater mortality in this group. These data provide strong support for recent guidelines advocating the use of tenofovir in all HIV-HBV-coinfected individuals initiating ART.

Trial registration: ClinicalTrials.gov NCT00342355.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / mortality
  • AIDS-Related Opportunistic Infections / physiopathology
  • Adult
  • Africa, Southern
  • Anti-Retroviral Agents / administration & dosage
  • Anti-Retroviral Agents / pharmacology*
  • CD4 Lymphocyte Count
  • Didanosine / administration & dosage
  • Didanosine / pharmacology*
  • Female
  • HIV-1 / drug effects*
  • Hepatitis B virus*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / mortality
  • Hepatitis B, Chronic / physiopathology
  • Humans
  • Kaplan-Meier Estimate
  • Lamivudine / administration & dosage
  • Lamivudine / pharmacology*
  • Male
  • Stavudine / administration & dosage
  • Stavudine / pharmacology*
  • Treatment Outcome

Substances

  • Anti-Retroviral Agents
  • Lamivudine
  • Stavudine
  • Didanosine

Associated data

  • ClinicalTrials.gov/NCT00342355