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 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.
Albrecht
M A
MA
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Hughes
M D
MD
Liou
S H
SH
Katzenstein
D A
DA
Murphy
R
R
Balfour
H H
HH
Para
M F
MF
Valdez
H
H
Hammer
S M
SM
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D016047:Zalcitabine / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine