Effect of lamivudine in HIV-infected persons with prior exposure to zidovudine/didanosine or zidovudine/zalcitabine

Nucleoside analog-based regimens remain an integral component of combinatio n therapy for use in both antiretroviral treatment-naive and experienced HI V-infected patients. To further define treatment responses to new antiretro viral therapy in patients with long-term experience to dual nucleoside anal og therapy (zidovudine [ZDV] plus didanosine [ddI] or ZDV plus zalcitabine [ddC]), 325 subjects derived from the AIDS Clinical Trials Group (ACTG) 175 trial were randomized to three different combination regimens: (1) continu ation of ZDV + ddI or ZDV + ddC (continuation arm), (2) addition of 3TC to ZDV + ddI or ZDV + ddC (addition arm), or (3) a switch to ZDV + 3TC therapy (switch arm). Both the addition and switch arms sustained significantly gr eater short-term (baseline to week 4) mean CD4(+) cell count increases comp ared with the continuation arm (+36, +28 versus -4 cells/mm(3); p = 0.012) and long-term CD4(+) cell count responses (baseline to weeks 40/48: +32, +1 9 versus -9 cells/mm(3); p = 0.003). Superior short-term (baseline to week 8) mean decreases in plasma HIV RNA (p<0.001) were achieved by both the add ition and switch arms (0.53 log(10) and 0.54 log(10) copies/ml, respectivel y) compared with the continuation arm (0.13 copies/ml) whereas no differenc es in long-term virologic suppression were observed (p = 0.30). At week 48, no differences were observed in the proportions of subjects who had HIV RN A levels below 500 copies/mL: 18% of subjects in each treatment arm (3-way p = 1.0). Overall, the treatments were well tolerated and only nine subject s (3%) died or developed one or more AIDS-defining events. While this study confirms the intrinsic antiretroviral activity of 3TC, only modest marker changes and limited short-term viral suppression are seen with incremental addition of the drug. The current approach of using 3TC in maximally suppre ssive regimens is preferred.