325   Low Two-Year Risk of Virologic Failure with First Regimen HAART.

R. Levy*, D. Labriola, and N. Ruiz.
DuPont Pharmaceuticals Co., Wilmington, DE.

Background:Concerns that virologic response to HAART may be of relatively short duration have led to consideration of delayed initiation of therapy. Current definitions of treatment failure often include discontinuation of therapy in patients with viral loads below limits of detection. However, only patients with virologic failure have lost therapeutic options since initiation of therapy.

Methods:DPC 006 is a multicenter, open-label, randomized study comparing efavirenz (EFV) + ZDV + 3TC, indinavir (IDV) + ZDV + 3TC and EFV + IDV in HIV-infected patients receiving their first HAART regimen. We compare the time to virologic failure, based on Kaplan-Meier estimates, by censoring discontinuations and CDC Category C events and only including confirmed viral loads >50 copies/mL (cpm) as virologic failure.

Results:1266 patients were enrolled (mean age 36.5 years, mean baseline viral load 60,250 cpm, mean baseline CD4 341 cells/mm³). Among the 422 patients randomized to EFV + ZDV + 3TC, 5% never achieved viral loads <50 cpm; 8% had a confirmed rebound to >50 cpm during the first 48 weeks and an additional 7% rebounded to >50 cpm between weeks 49 and 96. After 2 years of therapy, 80% of patients maintained virologic response. Among the 415 patients randomized to IDV + ZDV + 3TC, 12% never achieved viral loads <50 cpm; 15% had a confirmed rebound to >50 cpm during the first 48 weeks and an additional 8% rebounded to >50 cpm between weeks 49 and 96. After 2 years of therapy, 65% of patients maintained virologic response. Among the 429 patients randomized to EFV + IDV, 14% never achieved viral loads <50 cpm; 19% had a confirmed rebound to >50 cpm during the first 48 weeks and an additional 7% rebounded to >50 cpm between weeks 49 and 96. After 2 years of therapy, 60% of patients maintained virologic response.

Conclusion:First regimen HAART, particularly a regimen of EFV + 2 NRTIs, leads to long-term virologic success. Second year results show no acceleration of the risk of virologic failure. If trends continue, the median duration of virologic success with the EFV + ZDV + 3TC regimen will exceed 6 years.