Week 96 efficacy and safety of darunavir/ritonavir monotherapy vs. darunavir/ritonavir with two nucleoside reverse transcriptase inhibitors in the PROTEA trial.
PROTEA is a randomized controlled trial to assess the efficacy and safety of darunavir/ritonavir (DRV/r) monotherapy as an alternative to triple therapy.



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 (NRTIs) (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].



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 CD4 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.



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 CD4 counts < 200 cells/μL.
Department of Infectious and Tropical Diseases, Hôpital Saint-Antoine, AP-HP, INSERM UMR S 1136, Paris, France.
P M
PM
Girard
National Institute for Infectious Diseases, L. Spallanzani IRCCS, Rome, Italy.
A
A
Antinori
Hospital University La Paz, IdiPAZ, Madrid, Spain.
J R
JR
Arribas
University Hospital, Bergamo, Italy.
D
D
Ripamonti
Biostatistics, Janssen R&D, Beerse, Belgium.
C
C
Bicer
Janssen EMEA, Issy-les-Moulineaux, France.
B
B
Netzle-Sveine
Janssen EMEA, Issy-les-Moulineaux, France.
B
B
Hadacek
Janssen EMEA, Neuss, Germany.
C
C
Moecklinghoff
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods; D000069454:Darunavir / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D000069454:Darunavir
HIV clinical trials; darunavir; nucleoside reverse transcriptase inhibitors; protease inhibitor monotherapy; ritonavir