by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
November 16, 2021
Maggiolo F, Gianotti N, Comi L, et al. Rilpivirine plus cobicistat-boosted darunavir as alternative to standard three-drug therapy in HIV-infected, virologically suppressed subjects: Final results of the PROBE 2 trial. Antiviral Therapy. 2021 Oct 27 (online before print). https://doi.org/10.1177/13596535211042226
PROBE 2 assessed the safety and efficacy of switching to rilpivirine (RPV) plus darunavir/cobicistat (DRV/c) among people stably suppressed on three-drug ART without HBV co-infection. 48-week final analysis results are presented here, involving 80 participants in the early switch group and 80 participants in the late switch group. Participants in the early switch group had been on cART for a median duration of 39 months (late switch group: 22 months); median duration of virologic suppression was 7 years. Approximately a third of participants were already receiving a RPV-containing regimen while ~13% were taking DRV/c. 70 (87.5%) participants in the early group and 76 (94.8%) in the late group maintained viral load < 50 copies/mL. Two individuals in the late group met criteria for confirmed virological withdrawal (CVW), however no treatment emergent resistance-associated mutations were identified. Both had been on F/TAF plus DRV/c prior to switch, and both experienced viral blips (~80 copies/mL) during the study’s first phase. Both resuppressed on a three-drug regimen. Quantitative ultrasound (QUS) of the dominant heel scans indicated small bone stiffness increases in the early group (47.5% of participants in this group were taking tenofovir disoproxil fumarate prior to switch). Modest serum lipid increases were observed but felt to be of little/no clinical relevance. When analyzed by pre-switch ART backbone, lipid changes were significant only when the withdrawn backbone included tenofovir disoproxil fumarate. No significant body weight changes were observed.
Despite having fewer than 200 participants and limited length of follow-up, results from this trial add information to previous studies (e.g., DARIL, DUAL, RIDAR) exploring safety and efficacy of rilpivirine and boosted darunavir. This combination might be an appealing switch/ simplification option for some PWH who wish to limit NRTI and INSTI exposure. Because individuals were excluded if they had documented evidence of major resistance-associated NNRTI or PI substitutions, and most participants transitioned to RPV plus DRV/c with well over 5 years of virologic suppression in place, the generalizability of this approach may be somewhat limited. Further, the drug interaction potential and tolerability of this regimen may also limit widespread use. Despite boosted darunavir’s high barrier to resistance, authors note that the two patients with CVW and earlier evidence of virologic blips had “indications of problematic adherence”: further detail regarding this observation, as well as additional studies of this combination, will help shed light on its potential role in the evolving landscape of two-drug switch strategies.
The author has no conflicts of interest to disclose.
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