330   Final 48-Week Results of a Phase II, Randomized Study of the Safety, Efficacy, and Pharmacokinetics of BIDvsTID Nelfinavir and Saquinavir in Combination with Lamivudine and Stavudine in HIV-Positive Women (Women First Trial).

K. Squires*¹, J. Currier², R. Clark³, C. Zorilla⁴, P. Grieger⁵, and M. Till⁶.
¹Univ. of Southern California, Los Angeles;²Univ. of California, Los Angeles;³Louisiana State Univ.;⁴Univ of Puerto Rico;⁵Mt. Vernon Hospital, New York, NY; and⁶Northwestern Univ.

Background:Women comprise one of the fastest rising populations at risk for HIV infection. However, there currently exists a lack of clinical trials involving women. Accordingly, this study was designed to compare the safety, efficacy, and PK profiles of BID nelfinavir (NFV) + saquinavir (SQV) + lamivudine (3TC) + stavudine (d4T) with a TID regimen among a cohort of HIV-infected women.

Methods:This was a randomized, multicenter clinical trial involving 68 HIV-infected women age>13 years. Patients were either antiretroviral-naive or had <1 mo cumulative time on 3TC or d4T. All patients had HIV RNA >10,000 at baseline. Patients were randomized to either NFV (1250 mg BID) + SQV-HGC (1000 mg BID) + 3TC + d4T ( n = 33) or NFV (750 mg TID) + SQV-HGC (600 mg TID) + 3TC + d4T ( n = 35). The primary efficacy parameter was change in HIV RNA from baseline. Safety and adverse event rates on therapy were assessed, as was PK analysis after 28 days of treatment. P values were calculated using Fisher's exact test.

Results:At 48 weeks, a median log₁₀HIV RNA change from baseline of -2.16 (SD = 0.70) was observed among 22 patients in the BID arm; there was a median -1.76 log₁₀reduction observed among 16 patients in the TID arm (SD = 0.98; P = 0.307). Final ITT:NC = F results were as follows: 60.6% of patients in the BID arm ( n = 33) and 44.8% of patients in the TID arm ( n = 29) had HIV RNA <400 at 48 weeks ( P = 0.214). Using AT analysis, 91% of patients in the BID arm and 81% of patients in the TID arm had HIV RNA <400 ( P = 0.632). The median CD4 cell counts increased 186.3 (SD = 172.1) and 169.8 (SD = 194.4) in the BID and TID arms, respectively ( P = 0.955). No significant differences were observed between the two arms with respect to virologic or immunologic responses. Patients in the BID arm had a higher mean and median NFV and SQV AUC and C_maxcompared to patients in the TID arm. Both regimens were well tolerated.

Conclusion:A combination regimen of BID or TID NFV + SQV-HGC + 3TC + d4T durably suppressed HIV RNA levels over 48 weeks in HIV-infected women.