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Salvage Therapy with Saquinavir SGC (SQV) in Combination with Ritonavir (RTV) or Nelfinavir (NFV) Plus Delavirdine (DLV), Adefovir Dipivoxil (ADV), or Both - ACTG 359 R. M. GULICK*1, X. J. HU2, S. A. FISCUS3, C. V. FLETCHER4, R. HAUBRICH5, H. CHENG2, S. LAGAKOS2, E. ACOSTA6 , R. SWANSTROM3, C. MILLS7, S. SNYDER8, M. FISCHL9 , C. PETTINELLI10, and D. KATZENSTEIN11 for the ACTG 359 Team.
1Cornell Univ., NY; 2Harvard Univ., Boston, MA; 3Univ. of North Carolina at Chapel Hill; 4Univ. of Minnesota, Minneapolis; 5Univ. of California at San Diego; 6Univ. of Alabama at Birmingham; 7Ohio State Univ., Columbus; 8Social & Scientific Systems, Rockville, MD; 9Univ. of Miami, FL; 10DAIDS/NIAID, Bethesda, MD; and 11Stanford Univ., Palo Alto, CA Background: Long-term response to salvage antiretroviral therapy is unknown.
Objectives: To compare six salvage antiretroviral regimens over 48 weeks.
Design: Prospective, randomized study of HIV+, NNRTI-naïve subjects who took >6 months of indinavir (IDV) with HIV RNA (Amplicor) 2000-200,000 copies (cps)/ml and were assigned to one of six treatment arms: A (SQV 400 mg bid/RTV 400 mg bid/DLV 600 mg bid), B (SQV/RTV/ADV 120 mg qd), C (SQV/RTV/DLV/ADV), D (SQV 800 mg tid/NFV 750 mg tid/DLV), E (SQV/NFV/ADV), F (SQV/NFV/DLV/ADV). Analyses used a 2 x 3 factorial design evaluating RTV vs. NFV, and DLV vs ADV vs DLV + ADV. The primary endpoint was HIV RNA <500 cps/ml at week (wk) 16. Subjects with a virologic response at wks 12-16 (HIV RNA <5000 cps/ml or >1 log10 below baseline) continued treatment to wk 48.
Results: 277 subjects with a median 14 months IDV and extensive prior nucleoside use, and baseline HIV RNA 31746 cps/ml and CD4 229/mm3 were enrolled. At 16 wks, the proportion with HIV RNA <500 cps/ml was 30% (77 of 254 subjects) with 33% (in arm A), 20% (B), 31% (C), 47% (D), 16% (E), and 38% (F). There was no difference between the RTV and NFV groups (p=0.51) or between the DLV and DLV + ADV groups (p=0.47). DLV groups had a higher proportion of subjects with viral load levels <500 cps/ml than ADV groups (p=0.003). Of subjects with a virologic response by wk 16, 76% at wk 24, 65% at wk 36, and 59% at wk 48 had HIV RNA <500 cps/ml.
Conclusions: In nucleoside- and IDV-experienced, NNRTI-naive subjects receiving salvage therapy, 30% decreased viral load levels to <500 cps/ml at 16 wks. In subjects with a virologic response by wk 16, 59% had viral load levels that remained suppressed at week 48.
Key Words: antiretrovirals, clinical trial, salvage therapy
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