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

Abstract

Nucleoside analog-based regimens remain an integral component of combination therapy for use in both antiretroviral treatment-naive and experienced HIV-infected patients. To further define treatment responses to new antiretroviral therapy in patients with long-term experience to dual nucleoside analog 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) continuation 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 greater short-term (baseline to week 4) mean CD4+ cell count increases compared with the continuation arm (+36, +28 versus -4 cells/mm3; p = 0.012) and long-term CD4+ cell count responses (baseline to weeks 40/48: +32, +19 versus -9 cells/mm3; p = 0.003). Superior short-term (baseline to week 8) mean decreases in plasma HIV RNA (p < 0.001) were achieved by both the addition and switch arms (0.53 log10 and 0.54 log10 copies/ml, respectively) compared with the continuation arm (0.13 copies/ml) whereas no differences 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 RNA 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 subjects (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 suppressive regimens is preferred.

• Authors: M A Albrecht, M D Hughes, S H Liou, D A Katzenstein, R Murphy, H H Balfour, M F Para, H Valdez, S M Hammer, ACTG 303 Study Team
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 16 Issue 14 Pg. 1337-44 (Sep 20 2000) ISSN: 0889-2229 [Print] United States
• PMID: 11018853 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Anti-HIV Agents
• RNA, Viral
• Reverse Transcriptase Inhibitors
• Lamivudine
• Zidovudine
• Zalcitabine
• Didanosine

Topics

• Adult
• Anti-HIV Agents (therapeutic use)
• CD4 Lymphocyte Count
• Didanosine (therapeutic use)
• Drug Therapy, Combination
• Female
• HIV Infections (drug therapy, virology)
• HIV-1 (isolation & purification, physiology)
• Humans
• Lamivudine (therapeutic use)
• Male
• RNA, Viral (blood)
• Reverse Transcriptase Inhibitors (therapeutic use)
• Treatment Outcome
• Zalcitabine (therapeutic use)
• Zidovudine (therapeutic use)