Efficacy of darunavir/ritonavir as single-drug maintenance therapy in patients with HIV-1 viral suppression: a randomized open-label non-inferiority trial, MONOI-ANRS 136

Background: Long-term maintenance strategies to avoid NRTI toxicity and reduce costs deserve to be evaluated in patients with suppressed HIV RNA viremia on combined antiretroviral therapy (cART).
Methods: Patients on cART with HIV RNA < 400 copies/mL for at least 18 months were, after an 8-week induction phase of DRV/r (600/100 mg bid), randomized to either continuing the triple-drug regimen (2NRTI+DRV/r) or switching to DRV/r monotherapy. Failure was defined as virologic failure (VF = 2 consecutive HIV RNA levels above 400 copies/mL), or modification/discontinuation of study treatment (Rx) by week 48. The trial had 80% power to show non-inferiority for the DRV/r arm (lower limit = -10%).
Results: 242 patients were enrolled in the induction phase and 225 patients were randomized. Patients were 76% male with a median age of 46 years and a median CD4 count of 599 cells/uL. In the primary efficacy analysis, Rx success by Week 48 (ITT and Per Protocol populations) was:
Response 2NRTI + DRV/r DRV/r Delta 90%CI
Rx success (PP) 102/103 (99.0%) 97/103 (94.2%) - 4.9% [- 9.0 to - 0.7%]
Rx success (ITT) 104/113 (92.0%) 98/112 (87.5%) - 4.5% [-11.2 to 2.1%]
- VF 0 /113 (0.0%) 3 /112 (2.7%)
- Rx modification 6 /113 (5.3%) 8 /112 (7.1%)
- Rx discontinuation 3 /113 (2.7%) 3 /112 (2.7%)
Modifications were due to SAE in 1 patient in the 2NRTI + DRV/r arm and in 3 patients in the DRV/r arm including one HIV encephalitis and one neurological symptoms possibly related to HIV, both possibly related to study treatments. No new mutation related to DRV resistance was found in the 3 patients with VF.
Conclusions: In the PP population, DRV/r monotherapy showed non-inferior efficacy versus 2NRTI + DRV/r although the ITT population provided slightly discordant results.

C. Katlama1, M.A. Valentin1, M. Algarte-Genin2, C. Duvivier3, S. Lambert-Niclot4, P.-M. Girard5, J.-M. Molina6, B. Hosten7, S. Pakianather2, G. Peytavin8, A.G. Marcelin4, P. Flandre2
1Pitié-Salpétrière University Hospital and INSERM U 943, Infectious Disease, Paris, France, 2INSERM U 943, Paris, France, 3Necker Hospital, Infectious Disease, Paris, France, 4Pitié-Salpétrière University Hospital and INSERM U 943, Virology Department, Paris, France, 5Saint Antoine Hospital, Infectious Disease, Paris, France, 6Saint Louis Hospital AP HP, Infectious Disease, Paris, France, 7Bicetre Hospital, Kremlin-Bicetre, France, 8Bichat Claude Bernard Hospital, Paris, France