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M. W. Kline*, C. V. Fletcher, J. C. Lindsey, T. Fenton, and the ACTG 397.
Team.Baylor Coll. of Med., Houston TX; Univ. of Minnesota, Minneapolis; and Harvard Sch. of Publ. Health., Boston MA.
Background:.The objective of this study was to evaluate the tolerance, safety, and activity of SQV, given in combination with nucleoside antiretroviral agents (NRTIs), with or without nelfinavir (NLF), in HIV-infected children aged 3—16 years.
Methods:Children were randomized 1:1 to two treatment arms: SQV (50 mg/kg TID) + 2 NRTIs (arm 1) or SQV (50 mg/kg BID) + NLF (55 mg/kg BID) + 1 or 2 NRTIs (arm 2). Patients were followed for a median of 48 weeks each.
Results:51 children were enrolled; 47 children who began study treatment are included in this analysis. The mean age was 9.8 years (range, 3.1 to 16.9 years). Most (83%) subjects previously had received NRTIs; almost half (47%) had a history of protease inhibitor therapy other than SQV or NLF. The median baseline plasma HIV RNA concentration and CD4 count were 4.7 log10copies/mL (range, 2.8 to 5.8 log10copies/mL) and 395 cells/mL (range, 3 to 2018 cells/mL), respectively. Both treatment regimens were well tolerated. 23% of children in arm 1 and 12% in arm 2 had grade 3 or greater toxicities, but no events were judged to be related to study treatment. Using methods to adjust for plasma HIV RNA concentrations of <400 copies/mL, average declines in concentrations were 1.86 (SE = 0.48) (arm 1) and 1.75 (SE = 0.32) (arm 2) log10copies/mL at study week 16. Trough plasma concentrations of SQV and NLF were consistently and significantly greater in subjects achieving virologic success. Median CD4 counts and CD4% increased over 48 weeks in both treatment arms. No deaths occurred.
Conclusions:Combination therapy with SQV is safe and well-tolerated in HIV-infected children. Optimization of virologic responses may require strategies to ensure adequate SQV trough plasma concentrations.
© 8th Conference on Retroviruses and Opportunistic Infections