Abstract 329 - Comparison of Time To Achieve HIV RNA <400 Copies/ mL and <50 copies/mL in a Phase III, Blinded, Randomized Clinical Trial of ABT-378/r vs. NFV in ARV-Naive Patients.

329 Comparison of Time To Achieve HIV RNA <400 Copies/ mL and <50 copies/mL in a Phase III, Blinded, Randomized Clinical Trial of ABT-378/r vs. NFV in ARV-Naive Patients.

M. King*, B. Bernstein, D. Kempf, J. Moseley, K. Gu, and E. Sun for the M98-863 Study Group.
Abbott Labs., Abbott Park, IL.

Background:Decreases in HIV RNA to <400 and <50 copies/mL (c/mL) are typically examined at week 24 as interim endpoints for comparative clinical trials. While week 24 is well established for the <400 c/mL endpoint, the appropriate time for the <50 c/mL endpoint has not been adequately characterized, since patients with high baseline (BL) viral load (VL) may not decline to <50 c/mL within 24 weeks even with maximal suppression of replication.

Methods:Study M98-863 is a phase III, multi-center, international, double-blind, randomized study of 653 ARV-naïve pts treated with either ABT-378/r 400/100 mg BID (N = 326) or nelfinavir (NFV) 750 mg TID (N = 327). All pts also received d4T and 3TC. Viral load was measured by ultrasensitive assay (LOQ = 50 c/mL) at weeks 24, 32, 40, and 48.

Results:By week 24, 93% of ABT-378/r pts and 88% of NFV pts had demonstrated at least one VL <400 c/mL. While only 1 additional pt first had VL <400 c/mL after week 24, 97 pts first demonstrated VL <50 c/mL after week 24. More ABT-378/r pts than NFV pts achieved VL <50 c/mL at week 24, although the difference was not statistically significant (65% vs. 60%, ITT M = F). Median BL VL for these pts was 72,000 c/mL. More ABT 378/r pts (63/74, 85%) than NFV pts (34/83, 41%) on study for >24 weeks first had VL <50 c/mL after week 24 (p < 0.001). Median BL VL for pts with first VL <50 c/mL after week 24 was 177,000 c/mL. Median BL VL for the 11 ABT-378/r pts and 49 NFV pts who never demonstrated VL <50 c/mL despite >24 weeks of therapy was 255,000 c/mL. A total of 84% of ABT-378/r pts enrolled in the study ever demonstrated VL <50 c/mL, compared to 71% of NFV pts (p < 0.001). At week 48, 83% of ABT-378/r pts and 68% of NFV pts had VL <50 c/mL (on treatment, p < 0.001).

Conclusions:Among pts who did not have VL <50 c/mL at week 24, significantly more ABT-378/r-treated pts than NFV-treated pts subsequently demonstrated VL <50 c/mL after week 24. Higher baseline VL levels were associated with longer time to achieve VL <50 c/mL. While 24 weeks may be sufficient for pts to reach <400 c/ mL, more than 24 weeks of therapy may be required to differentiate between potent antiretroviral regimens at <50 c/mL.