LB7 A Randomized, Placebo-Controlled Trial of Saquinavir (SQV)sgc, Indinavir (IDV) or Nelfinavir (NFV) in Combination with Amprenavir (APV), Abacavir (ABC), Efavirenz (EFZ) & Adefovir (ADV) in Patients (Pts) with Protease Inhibitor (PI) Failure
S. HAMMER*, J. MELLORS, F. VAIDA, K. BENNETT, V. DEGRUTTOLA, L. SHEINER and the ACTG 398 STUDY TEAM. NIAID-Sponsored AIDS Clin. Trials Group, Bethesda, MD.
ACTG 398 assessed whether a 2nd PI, combined with APV, ABC, EFZ and ADV, would improve virologic response in PI-exp pts with HIV RNA >1,000 c/ml. 481 pts with 1-3 PI-exp (SQV, IDV, RTV &/or NFV) were selectively randomized, based on prior PI-exp, to 1 of 4 arms: (1) SQVsgc 1600 mg bid; (2) IDV 1200 mg bid; (3) NFV 1250 mg bid; or (4) 2nd PI Placebo (Plac). Enrollment was also stratified by NNRTI-exp. All pts rec'd APV 1200 mg bid, ABC 300 mg bid, EFZ 600 mg qD and ADV 60 mg qD (with L-carnitine). Analysis was ITT with primary endpt defined as failure to achieve and sustain an HIV RNA <200 c/ml by wk 24, missing RNA, or loss to f/u. At baseline: 87% were men; 58% white, 23% Afr-Amer, 15% Hisp; 44% NNRTI-exp; median age 40 yrs, CD4 count 202/mm3 & HIV RNA 51,601 c/ml. At 24 wks, the off study rate was 7% & the off treatment rates for toxicity and early virologic failure were 33% & 19%, respectively. 66% (316/481) reached the primary endpt. Endpt rates were comparable among the SQV, IDV & NFV arms (65%, 62% & 61%, respectively); in the Plac arm it was 72%. The endpt rate of the dual PI arms (combined) was significantly lower than the APV alone arm (P=0.02). The endpt rate was also significantly lower among NNRTI-naïve vs. exp pts (55% vs. 80%, respectively, P<0.001), but was not different among single vs. multiple PI-exp pts. With a median f/u of 40 wks, rates of grade 3-4 toxicities were not different across arms. GI symptoms, hypertriglyceridemia & hypophosphatemia predominated. In conclusion: (1) HIV RNA suppression to <200 c/ml at 24 wks was achieved in only 34% of pts despite 4-5 new agents; (2) overall the dual PI arms were superior to the single PI arm; (3) prior NNRTI-exp was significantly associated with treatment failure but prior PI-exp (1 vs. >2) was not; & (4) high off treatment rate indicates more effective and better tolerated salvage regimens are needed.
Conference on Retroviruses and Opportunistic Infections,