ObjectivesLong-term nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment failure in most developing countries has led to broad cross-resistance within NNRTI and nucleoside reverse transcriptase inhibitor (NRTI) classes. In this study, we investigated the efficacy and tolerability of a double boosted protease inhibitor (PI) regimen in this setting.MethodsA total of 64 HIV-infected patients who had failed NNRTI-based regimens were randomized to receive either lopinavir/saquinavir/ritonavir [LPV/SQV/r; 400/1000/100mg twice a day (bid)] alone or indinavir/ritonavir (IDV/r; 800/100mg bid) plus two NRTIs optimized with genotypic drug resistance guidance. Patients who had no available optimized NRTI backbone were allocated to the LPV/SQV/r arm.ResultsAt 48 weeks, the percentages of patients with plasma viral loado50 HIV-1 RNA copies/mL were 60% (31 of 52 patients) in the LPV/SQV/r arm vs 50% (six of 12) in the IDV/r/2NRTIs arm in the intent-totreat (ITT) analysis, and 61% (31 of 51) vs 71% (five of seven), respectively, in the as-treated analysis. The median (interquartile range) increases in absolute CD4 cell count from baseline were 177 (91–269) and 100 (52–225) cells/mL in the LPV/SQV/r and IDV/r/2NRTIs groups, respectively (P50.32). Four of 12 patients (33%) in the IDV/r/2NRTIs group experienced severe nausea and vomiting and four patients (8%) in the LPV/SQV/r group had significant hepatitis.ConclusionsLPV/SQV/r and high-dose boosted IDV were not well tolerated and led to o65% ITT virological efficacy outcomes. A randomized larger scale study with new formulations and/or more tolerable boosted PIs in NNRTI-based failure is warranted.

HIV Medicine ปี 2550, November ปีที่: 8 ฉบับที่ 8 หน้า 529-535

Thailand, Double boosted protease inhibitor, Nonnucleoside reverse transcriptase inhibitor resistance, Salvage therapy