Efficacy of PI monotherapy versus triple therapy for 1964 patients in 10 randomised trials

Abstract

Introduction: The efficacy of protease inhibitor monotherapy has been analyzed with different endpoints: initial HIV-1 RNA rebound, long-term HIV-1 RNA suppression after re-intensification, treatment-emergent drug resistance, neurocognitive testing and HIV-1 RNA in the cerebrospinal fluid (CSF). Methods: A PUBMED search identified nine randomised trials of PI monotherapy versus triple therapy in patients with HIV RNA B50 copies/mL at baseline. Results from the recently completed PROTEA trial were also included. The percentage of patients with HIV RNA suppression B50 copies/mL was analyzed using switch equals failure and intensification included endpoints (ITT). The number of patients with new drug resistance mutations, HIV RNA in the CSF or change in neurocognitive function was analyzed by treatment arm. Results: Four trials evaluated darunavir/r monotherapy (n 0785: MONET, MONOI, MONARCH, PROTEA), five evaluated lopinavir/r monotherapy (n 0592: OK-04, KalMo, KALESOLO, KRETA, MOST) and one evaluated both (MRC PIVOT, n0587). HIV-1 RNA suppression rates tended to be lower on PI monotherapy than triple therapy in ''switch equals failure'' analysis (76% vs 82%), but not when the outcome of intensification was included (87% vs 85%). There were small numbers of patients taking PI monotherapy with detectable HIV-1 RNA in the CSF, in three trials: PROTEA (n 02), MONOI (n 02) and MOST (n 05), but only two cases of CSF viral escape (MONOI). In two trials, there was no difference in neurocognitive test results between PI monotherapy and triple therapy, based on z-scores from five domains (in PROTEA, mean change in NPZ-5 score00.0 for DRV/r Copyright: – 2014 Arribas J et al; licensee International AIDS Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Table 1. Number of patients with treatment emergent NRTI, NNRTI or PI resistance mutations NRTI or PI Resistance mutations Trial (n, duration) PI/r Triple therapy LPV/r trials OK-04 (n0200, 96 wks) 2/100 2/98 Kalmo (n 060, 96 wks) 0/30 0/30 Kalesolo (n 0186, 48 wks) 0/87 0/99 KRETA (n 088, 48 wks) 1/44 0/44 MOST (n 060, 24 wks) 0/29 0/31 DREAM (n 0197, 96 wks) 3/11 DRV/r trials MONET (n 0256, 144 wks) 1/127 1/129 MONOI (n 0246, 96 wks) 0/112 0/113 Monarch (n 030, 48 wks) 0/15 0/15 PROTEA (n 0273, 48 wks) 0/137 0/136 Mixed PI trials PIVOT (n 0587, 5 years) 7/291 4/296