Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Rapid-Initiation Model of Care for Human Immunodeficiency Virus Type 1 Infection: Primary Analysis of the DIAMOND Study

Abstract

Background Most guidelines recommend rapid treatment initiation for patients with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection, but prospective US data are limited. The DIAMOND (NCT03227861) study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a phase 3 prospective study evaluating efficacy/safety of a single-tablet regimen in a rapid-initiation model of care. Methods Adults aged ≥18 years began D/C/F/TAF ≤14 days from diagnosis without screening/baseline results; as results became available, participants not meeting predefined safety/resistance stopping rules continued. Primary endpoint was virologic response (HIV-1 RNA <50 copies/mL; intent-to-treat; US Food and Drug Administration [FDA] snapshot) at week 48; participant satisfaction was measured via the HIV Treatment Satisfaction Questionnaire status version (HIVTSQs). Results Of 109 participants, 87% were male, 32% black/African American, median (range) age was 28 (range, 19–66) years, 25% of participants had HIV-1 RNA ≥100 000 copies/mL, 21% had CD4+ cell count <200 cells/µL, and 31% enrolled ≤48 hours from diagnosis. At week 48, 97 (89%) participants completed the study and 92 (84%) achieved HIV-1 RNA <50 copies/mL (FDA snapshot). There were no protocol-defined virologic failures; incidences of adverse events (AEs) and adverse drug reactions (33%) were low, no serious AEs were study drug related, and 1 (<1%) participant discontinued due to study drug related AE(s). The overall HIVTSQs score at week 48 was 58 (maximum: 60). Conclusions At week 48, a high proportion of participants starting D/C/F/TAF achieved HIV-1 RNA <50 copies/mL and very few discontinued therapy. D/C/F/TAF was well tolerated, no participants discontinued due to baseline resistance stopping criteria, and high treatment satisfaction among participants was recorded. Clinical Trials Registration NCT03227861.

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

“…These clinical trials were conducted over more than a 10-year span, providing 5291 patientyears of experience with this regimen. 20,21,23,30 A limitation of the analysis is that the studies did not include integrase inhibitor-based regimens, which were not available at the time that some of the studies in this analysis took place. Additionally, the analysis reported here only includes data from controlled clinical trials and does not include real-world data.…”

“…Methodological details for the seven clinical studies included in the previous analysis have been described. 6,[10][11][12][13][14][15][16] Detailed methods for the three recent studies of the D/C/F/TAF STR have also been reported [19][20][21][22][23] and are briefly summarized here. Key study design information for all 10 studies is shown in Supplemental Figure S1.…”

“…All 109 patients from DIAMOND were included in the current analysis. 21 EMERALD was a 96-week study in treatment-experienced adults who were virologically suppressed on a boosted PI þ emtricitabine/TDF regimen. Patients were enrolled and randomly assigned to either immediately switch to D/C/F/TAF at baseline (n ¼ 763) or remain on their existing regimen (control arm; n ¼ 378) through the primary analysis time point of Week 48.…”

“…Details of the resistance analyses performed in the 10 studies have been described. 6,[19][20][21][22][23] Post-baseline resistance testing was performed for patients who experienced protocol-defined virologic failure (PDVF; i.e. nonresponse, virologic rebound, and/or viremic at endpoint).…”

“…3,18 Reported here is an extension of a previous evaluation of post-baseline HIV-1 resistance data from seven phase 2 or 3 clinical studies (1686 patients) of darunavir 800 mg QD-based ARV regimens. 6 The current analysis incorporates post-baseline findings from three recent studies of the darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/ 200/10 mg QD STR [19][20][21][22][23] to evaluate resistance across a total of 10 clinical studies of darunavir 800 mg QDbased regimens.…”