Pooled resistance analyses of darunavir once-daily regimens and formulations across 10 clinical studies of treatment-naïve and treatment-experienced patients with human immunodeficiency virus-1 infection

Background The efficacy and high barrier to resistance of darunavir have been demonstrated across diverse populations with HIV-1 infection. Objective To evaluate post-baseline resistance among patients in studies of once-daily (QD) darunavir-based regimens and formulations. Methods The analysis included treatment-naïve and virologically failing or suppressed patients from 10 phase 2/3 studies (48–192 weeks in duration) of boosted darunavir 800 mg QD-based regimens. Three were phase 3 studies of the QD darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg single-tablet regimen. Post-baseline resistance was evaluated upon protocol-defined virologic failure (PDVF). Resistance-associated mutations (RAMs) were identified using International Antiviral Society-USA mutation lists. Phenotypic analyses varied across studies. Results Overall, 250 of 3635 patients in the analysis met PDVF criteria; 205 had post-baseline genotypes/phenotypes. In total, four (0.1%) patients developed (or had identified) ≥1 darunavir and/or primary protease inhibitor (PI) RAM; only one (10 years, loss of phenotypic susceptibility to darunavir was only observed once in a PI-experienced patient and has never been observed in treatment-naïve patients, treatment-experienced PI-naïve patients, or treatment-experienced virologically suppressed patients

Rapid initiation of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in acute and early HIV-1 infection: a DIAMOND subgroup analysis

Background: Treatment during acute or early human immunodeficiency virus (HIV)-1 infection is associated with immunologic and virologic benefits. Objective: To evaluate darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) efficacy/safety among patients with acute or early HIV-1 infection who rapidly initiate treatment. Methods: DIAMOND (ClinicalTrials.gov Identifier: NCT03227861), a phase 3 study, evaluated the efficacy/safety of D/C/F/TAF 800/150/200/10 mg in rapid initiation. Adults aged ≥18 years began D/C/F/TAF within 14 days of diagnosis, prior to the availability of screening/baseline laboratory results. In this subgroup analysis, virologic response (HIV-1 RNA <50 copies/mL) was assessed at Week 48 by intent-to-treat FDA snapshot (ITT-FDA snapshot) and observed (excluding patients with missing data) analyses in patients with acute (HIV-1 antibody negative and HIV-1 RNA positive/p24 positive) or early (HIV-1 antibody positive and suspected infection ≤6 months before screening/baseline) infection. Results: Among 109 patients, 13 had acute and 43 had early HIV-1 infection. High rates of virologic response were demonstrated at Week 48 by ITT-FDA snapshot (acute: 10/13 [76.9%]; early: 37/43 [86.0%]) and observed (acute: 10/11 [90.9%]; early: 37/38 [97.4%]) analyses. No patients discontinued or required regimen change due to baseline resistance or lack of efficacy, or developed protocol-defined virologic failure. Through Week 48, 7 (53.8%) acute and 22 (51.2%) early infection patients had a D/C/F/TAF-related adverse event (AE); none had a D/C/F/TAF-related grade 4 or serious AE. Conclusions: High rates of viral suppression during acute/early infection were achieved with D/C/F/TAF rapid initiation, no treatment-emergent resistant mutations were observed, and D/C/F/TAF was safe and well tolerated