41. A Randomized Trial Comparing 2 4-Drug Antiretroviral Regimens with a 3-Drug Regimen in Advanced HIV Disease

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Session 13 Oral Abstract Session
Antiretroviral Chemotherapy: Combination Therapy, Drug Resistance, and Treatment Interruption
Session Time: Tuesday, 10 am - 12:30 pm
Room 4B

10:00 41.

A Randomized Trial Comparing 2 4-Drug Antiretroviral Regimens with a 3-Drug Regimen in Advanced HIV Disease
M. Fischl*¹, H. Ribaudo², A. C. Collier³, A. Erice⁴, M. Giuliano⁵, M. Dehlinger⁶, J. J. Eron⁷, M. Saag⁸, S. Hammer⁹, S. Vella⁵, and J. Feinberg¹⁰ for the AIDS Clinical Trials Group 388 Team
¹Univ. of Miami, FL; ²Harvard Univ., Boston, MA; ³Univ. of Washington, Seattle; ⁴Univ. of Minnesota, Minneapolis; ⁵Inst. Superiore, Rome, Italy; ⁶NIAID, NIH, Bethesda, MD; ⁷Univ. of North Carolina, Chapel Hill; ⁸Univ. of Alabama, Birmingham; ⁹Columbia Univ. Coll. of Physicians and Surgeons, New York, NY; and ¹⁰Univ. of Cincinnati, OH

Background: Optimal treatment for advanced HIV infection is not well defined.
Methods: ACTG 388 was a phase III open-label randomized study of lamivudine (3TC) and zidovudine (ZDV) with either indinavir (IDV), efavirenz (EFV)+IDV, or nelfinavir (NFV)+IDV, in patients with no previous antiretroviral or limited nucleoside therapy, and plasma HIV-1 RNA =80,000 copies/ml or CD4 =200 cells/mm³. The primary endpoint was time to confirmed virologic failure. The analysis was intent-to-treat.
Results: 517 subjects (173 EFV+IDV, 176 NFV+IDV, and 168 IDV) were enrolled. 81% were men, 48% white, 32% black, and 17% Hispanic. Mean baseline CD4 and HIV-1 RNA were 161 cells/mm³ and 5.42 log₁₀copies/mL. Median follow-up was 2.1 years. 172 subjects had virologic failure (39 EFV+IDV, 81 NFV+IDV, and 52 IDV). Compared to IDV, a lower rate of virologic failure occurred with EFV+IDV (p=0.04) and a higher rate with NFV+IDV (p=0.006). Probability of response (< 200 HIV-1 RNA copies/mL) by week 24 was 87% with EFV+IDV, 78% with NFV+IDV, and 86% with IDV. Among responders, there was a lower rate of relapse with EFV+IDV (p=0.009) and no significant difference with NFV+IDV (p=0.33), compared with IDV. CD4 increased in all groups. 126 had grade 3 or 4 signs/symptoms (41 EFV+IDV, 50 NFV+IDV, and 35 IDV). 178 had grade 3 or 4 lab abnormalities (58 EFV+IDV, 63 NFV+IDV, and 57 IDV). No significant differences were seen in the rates of grade 3 or 4 adverse events between EFV+IDV and IDV (p=0.97), and a suggestion of an increased rate between NFV+IDV, and IDV (p=0.07).
Conclusions: Treatment with EFV, IDV, 3TC, and ZDV was well tolerated and resulted in a superior virologic response and is an option for advanced HIV disease. In contrast, treatment with NFV, IDV, 3TC, and ZDV resulted in an inferior virologic response and a greater likelihood of toxicity, compared to the 3-drug regimen.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections