AVANTI 2. Randomized, double-blind trial to evaluate the efficacy and safety of zidovudine plus lamivudine versus zidovudine plus lamivudine plus indinavir in HIV-infected antiretroviral-naive patients.
OBJECTIVE
To investigate the effect of combination antiretroviral therapy on plasma HIV-1 RNA as measured by HIV RNA PCR and to assess their safety and tolerability.


METHODS
A randomized, multicentre, double-blind, placebo-controlled trial.


METHODS
Multicentre study in eight European countries, Australia and Canada.


METHODS
Antiretroviral naive patients (n = 103) with CD4 cell counts between 150 and 500 x 10(6)/l.


METHODS
Patients were randomly assigned to zidovudine (ZDV; 200 mg three times per day) plus lamivudine (3TC; 150 mg twice per day) or to ZDV + 3TC + indinavir (IND; 800 mg q8h) for 52 weeks.


METHODS
Degree and duration of reduction of plasma HIV-1 RNA as measured by RNA PCR; Development of drug-related toxicities sufficiently severe to warrant dose modification, interruption or permanent discontinuation.


RESULTS
ZDV + 3TC + IND reduced plasma HIV-1 RNA (P < 0.001) and increased CD4 cell count significantly (P = 0.01) more than ZDV + 3TC. The addition of IND to ZDV + 3TC as initial therapy markedly increased the proportion of patients with plasma HIV-1 RNA values < 500 copies/ml (31/52, 60%) or 20 copies/ml (24/52, 46%) as compared with ZDV + 3TC (9/50, 18% or 2/50, 4% respectively) at week 52 in an intention-to-treat, missing = failure analysis. Assessment of time to virological rebound (> 0.5 log10 copies/ml above nadir) showed that patients who attained a minimum plasma HIV-1 RNA of < or = 20 copies/ml were less likely to rebound than those who did not reach this threshold. The addition of IND to ZDV + 3TC did not result in any significant increase in adverse experiences.


CONCLUSIONS
ZDV + 3TC + IND resulted in a considerable improvement compared with the double combination, in reduction in plasma HIV-1 RNA, increase in CD4 cell count and proportion of patients with HIV RNA below the limit of detection. Despite an average 3 log10 decrease in plasma HIV-1 RNA on triple therapy, however, maximal suppression (< or = 20 copies/ml) was only attained in about one-half of the patients in an intent-to-treat analysis.
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010349:Patient Compliance; D010919:Placebos; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D010919:Placebos; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir