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Week 96 efficacy and safety of darunavir/ritonavir monotherapy vs. darunavir/ritonavir with two nucleoside reverse transcriptase inhibitors in the PROTEA trial
Author(s) -
Girard PM,
Antinori A,
Arribas JR,
Ripamonti D,
Bicer C,
NetzleSveine B,
Hadacek B,
Moecklinghoff C
Publication year - 2017
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12386
Subject(s) - darunavir , medicine , ritonavir , adverse effect , discontinuation , viral load , randomized controlled trial , gastroenterology , combination therapy , pharmacology , virology , human immunodeficiency virus (hiv) , antiretroviral therapy
Objectives PROTEA is a randomized controlled trial to assess the efficacy and safety of darunavir/ritonavir ( DRV /r) monotherapy as an alternative to triple therapy. Methods Patients fully suppressed on first‐line antiretrovirals (viral load < 50 HIV ‐1 RNA copies/ mL ) were switched to DRV /r 800/100 mg once daily, either as monotherapy ( n = 137) or with two nucleoside reverse transcriptase inhibitors ( NRTI s) ( n = 136). Treatment failure was HIV ‐1 RNA level ≥ 50 copies/ mL at week 96 or discontinuation of study treatment [Food and Drug Administration ( FDA ) snapshot algorithm]. Results Patients were mainly male and white, with mean age 44 years. In the primary efficacy analysis, the percentage of patients with HIV ‐1 RNA < 50 copies/ mL by week 96 [intent to treat ( ITT )] was lower in the DRV /r monotherapy arm (103 of 137 patients; 75%) than in the triple therapy arm (116 of 136 patients; 85%) [difference −10.1%; 95% confidence interval ( CI ) −19.5, −0.7%]. In the switch‐included analysis, monotherapy was noninferior to triple therapy. In a post hoc analysis, for patients with nadir CD 4 count ≥ 200 cells/μL, rates of HIV ‐1 RNA suppression were 82 of 96 patients (85%) in the DRV /r monotherapy arm and 88 of 106 patients (83%) in the triple therapy arm. No treatment‐emergent primary protease inhibitor mutations were detected in either arm. The frequency of adverse events was similar in the two arms; however, one patient in the monotherapy arm was hospitalized with HIV encephalitis and elevated cerebrospinal fluid HIV ‐1 RNA . Conclusions In this study, in patients with HIV ‐1 RNA < 50 copies/ mL at baseline, switching to DRV /r monotherapy showed lower efficacy vs. triple therapy at week 96 in the primary ITT switch‐equals‐failure analysis, particularly in patients with CD 4 counts < 200 cells/ μ L.