Evolution of lamivudine-resistant hepatitis B virus and HIV-1 in co-infected individuals: an analysis of the CAESAR study

Objectives: Lamivudine has potent activity against HIV-1 and hepatitis B vi rus (HBV). Go-infection with these two viruses is common, and this may ther efore influence the choice of antiretroviral therapies; A cohort of co-infe cted patients treated with lamivudine were studied in order to evaluate the differential effects of lamivudine on the two viral populations within the same individual after 44-52 weeks of therapy. Design and methods: Retrospective virological analysis of an HIV-1/HBV co-i nfected lamivudine cohort derived from a randomized, placebo-controlled stu dy of lamivudine in HIV infection, the CAESAR study. Results: Five of thirteen patients with HBV viral load > 10 000 copies/mt a fter 44-52 weeks of lamivudine therapy had genotypic drug resistance. Four of these five had a rebound of viral replication over the period of study a nd in one case this was associated with an alanine transaminase serum eleva tion. Ten of the thirteen patients had a 44-52 week HIV viral load > 1000 c opies/ml, all of whom also had HIV reverse transcriptase M184V or M1841 mut ations. Conclusions: Extrapolating these results to the population yields an estima ted 1-year incidence of drug-resistant HBV of at least 14% in lamivudine-tr eated HIV-1/HBV coinfected patients. The clinical and virological benefit o f HBV lamivudine monotherapy in co-infected patients should be balanced aga inst the potential for emergence of drug resistance. Further, these data su ggest that the determinants of HIV and HBV drug resistance are different an d that parallel evolution, rather than cc-evolution of HBV and HIV-1 in co- infected individuals occurs. (C) 2000 Lippincott Williams & Wilkins.