ORIGINAL RESEARCH Efficacy and tolerability of a double boosted protease inhibitor (lopinavir 1 saquinavir/ritonavir) regimen in HIV- infected patients who failed treatment with nonnucleoside reverse transcriptase inhibitors P Chetchotisakd, 1 S Anunnatsiri, 1 P Mootsikapun, 1 S Kiertiburanakul, 2 T Anekthananon, 3w C Bowonwatanuwong, 4 B Kowadisaiburana, 5 K Supparatpinyo, 6 K Ruxrungtham 7,8w and the study team* 1 Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, 2 Ramathibodi Hospital and, 3 Siriraj Hospital, Mahidol University, Bangkok, Thailand, 4 Chonburi Hospital, Chonburi, Thailand, 5 Bamrasnaradura Institute, Nonthaburi, Thailand, 6 Chiang Mai University Hospital, Chiang Mai University, Chiang Mai, Thailand, 7 King Chulalongkorn Memorial Hospital, Chulal- ongkorn University, Patumwan, Bangkok, Thailand, and 8 the HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand Objectives Long-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. Methods A 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; 800/100 mg 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. Results At 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-to- treat (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 (P 5 0.32). 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. Conclusions LPV/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. Keywords: double boosted protease inhibitor, nonnucleoside reverse transcriptase inhibitor resistance, salvage therapy, Thailand Received: 4 July 2007, accepted 26 July 2007 Introduction Since highly active antiretroviral therapy (HAART) for HIV infection became available, the rates of mortality and morbidity associated with HIV disease have declined [1,2]. The recommended first-line antiretroviral (ARV) combina- tions for HIV-infected persons are two nucleoside reverse transcriptase inhibitors (NRTIs) as a backbone plus either Correspondence: Ploenchan Chetchotisakd, Srinagarind Hospital, Khon Kaen University, Khon Kaen 40002, Thailand. e-mail: ploencha@kku.ac.th *See Appendix A. w Potential conflicts of interest: Kiat Ruxrungtham and Thanomsak Anekthananon received research grant support from the Government Pharmaceutical Organization (GPO), which manufactures GPOVIR s . Kiat Ruxrungtham has also been a consultant for, and received an honorarium and research grants from, Abbott, Roche and Merck, and has spoken at conferences sponsored by these companies. r 2007 British HIV Association HIV Medicine (2007), 8, 529–535 529