338   Durability of Salvage Therapy with Saquinavir SGC (SQV) in Combination with Ritonavir (RTV) or Nelfinavir (NFV) plus Delavirdine (DLV), Adefovir Dipivoxil (ADV), or Both- —ACTG 359: 48-Week Final Results.

R. M. Gulick*¹, X. J. Hu², S. Fiscus³, C. V. Fletcher⁴, R. Haubrich⁵, H. Cheng⁶, S. Lagakos⁶, E. Acosta⁷, R. Swanstrom³, C. Mills⁸, S. Snyder⁹, M. Fischl¹⁰, C. Pettinelli¹¹, and D. Katzenstein¹²for the ACTG 359 Team.
¹Cornell Univ.;²Univ. of Memphis;³Univ. of North Carolina;⁴Univ. of Minnesota;⁵Univ. of California, San Diego;⁶Harvard Univ.;⁷Univ. of Alabama;⁸Ohio State Univ.;⁹Social & Scientific Systems, Rockville, MD;¹⁰Univ. of Miami;¹¹DAIDS/NIAID, Bethesda, MD; and¹²Stanford Univ.

Background:Long-term HIV RNA and CD4 responses to HIV "salvage therapy" are unknown.

Methods:Prospective, randomized, partially blinded study of NNRTI-naïve subjects who took>6 months of indinavir (IDV) with HIV RNA 2000—200,000 copies (cps)/ml, assigned to open-label SQV/RTV or SQV/NFV together with blinded DLV, ADV, or both. The primary study endpoint was the proportion of subjects with HIV RNA<500 cps/ml at week (wk) 16 (intent-to-treat analysis). Subjects with a virologic response (HIV RNA <5000 cps/ml or>1 log₁₀below baseline) at wks 12—16 were eligible to continue treatment through wk 48.

Results:277 subjects with a median 14 months prior IDV, baseline HIV RNA 31746 cps/ml and CD4 229/mm³completed 16 wks of study treatment. At 16 wks, the proportion with HIV RNA<500 cps/ml was 30% (77 of 254 subjects) and the median change from baseline CD4 was +18 cells/mm³(n = 253, range -342 to +953 cells/ mm³). At wk 24, 134 subjects entered the 24-wk treatment extension. 29 of them were ineligible based on the protocol definition of virologic response and were excluded from the analyses. 84 of the 105 eligible subjects completed 48 wks of follow-up. Of 105 eligible extension subjects, 70 had HIV RNA<500 cps/ml at wk 16 and 61% of them (43 of 70) had sustained virologic suppression (<500 cps/ml)at wk 48. The median change from baseline CD4 at wk 48 was +72 cells/mm³(n = 84, range -192 to +808 cells/mm³): +102 cells/mm³in subjects with HIV RNA<500 (n = 49) vs. +20 cells/mm³in subjects with HIV RNA >500 (n = 35) (p = 0.033).

Conclusions:61% of subjects receiving salvage therapy with HIV RNA<500 cps/ml at 16 weeks remained virologically suppressed (<500 cps/ml) at week 48. CD4 cell counts increased through 48 weeks in subjects taking salvage therapy with continued virologic suppression.