Open AccessThe PROTEA trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV‐1 RNA below 50 copies/mL
Author(s) -
Antinori Andrea,
Arribas Jose,
Fehr Jan,
Girard PierreMarie,
Horban Andrzej,
Hill Andrew,
Delft Yvon,
Moecklinghoff Christiane,
Hill Andrew
Publication year - 2014
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.17.4.19525
Subject(s) - darunavir , medicine , ritonavir , gastroenterology , combination therapy , viral load , pharmacology , virology , antiretroviral therapy , human immunodeficiency virus (hiv)
In previous studies, protease inhibitor (PI) monotherapy has shown trends for higher low‐level elevations in HIV‐1 RNA compared to triple therapy, but no increase in the risk of drug resistance. Methods A total of 273 patients with HIV‐1 RNA <50 copies/mL for over 24 weeks on current antiretrovirals switched to DRV/r (darunavir/ritonavir) 800/100 mg once‐daily, either as monotherapy ( n =137) or with 2NRTIs (nucleoside reverse‐transcriptase inhibitors) ( n =136), after a 4 week run‐in phase with DRV/r + 2NRTI. Treatment failure was defined as HIV‐1 RNA levels above 50 copies/mL (FDA Snapshot method) by Week 48, or switches off study treatment. Patients with elevations in HIV‐1 RNA on DRV/r monotherapy could be re‐intensified with NRTIs. The trial had 80% power to show non‐inferiority for the monotherapy arm (delta = − 12%). Results Patients were 83% male and 87% Caucasian, with mean age 42 years; 10% were HCV antibody positive. In the DRV/r monotherapy arm, there were more patients with nadir CD4 count below 200 cells/µL (30% versus 22%). In the primary efficacy analysis, HIV‐1 RNA <50 copies/mL by Week 48 (intent‐to‐treat (ITT)) was 118/137 (86.1%) in the DRV/r monotherapy arm versus 129/136 (94.9%) in the triple therapy arm; DRV/r monotherapy did not show non‐inferiority versus triple therapy in the primary analysis (difference=− 8.7%, 95% CI −15.5 to −1.8%). In the multivariate analysis, the main predictor of treatment failure was nadir CD4 count. For patients with nadir CD4 counts <200 cells/µL, HIV‐1 RNA suppression rates at Week 48 were 27/41 (66%) in the DRV/r monotherapy arm and 29/30 (97%) in the triple therapy arm; for patients with CD4 nadir at least 200 cells/µL, HIV‐1 RNA suppression rates were 91/96 (95%) in the DRV/r monotherapy arm and 100/106 (94%) in the triple therapy arm. In the overall population, by a switch included analysis, efficacy was 92.0% versus 96.3%, showing non‐inferiority (difference=− 4.3%, 95% CI=−9.7 to +1.2%). No treatment‐emergent primary PI mutations were detected in three patients with sustained elevations in HIV‐1 RNA at least 400 copies/mL (two on PI monotherapy, one on triple therapy). CD4 counts remained stable during the trial in both arms. Conclusions In this study for patients with HIV‐1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple antiretroviral therapy at Week 48 in the primary switch equals failure analysis (86% versus 95%). However, this lower efficacy was seen mainly in patients with CD4 nadir levels below 200 cells/µL. There was no development of PI resistance.