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.

Keywords: D/C/F/TAF; HIV-1; darunavir; rapid initiation; single-tablet regimen.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide virologic efficacy in a rapid-initiation model of care. A, Virologic response at week 48. aThree participants discontinued early due to protocol-defined safety stopping rules. B, Log10 human immunodeficiency virus type 1 (HIV-1) RNA over time for individual participants with HIV-1 RNA ≥50 copies/mL at week 48 (observed analysis; n = 4). HIV-1 RNA level was not available for 1 participant at the week 2 visit. The participant with HIV-1 RNA 144 000 000 copies/mL at screening/baseline was a 30-year-old black/African American man with a CD4+ cell count of 242 cells/µL, Centers for Disease Control and Prevention (CDC) classification stage A, World Health Organization (WHO) clinical stage 1 (asymptomatic), and acute infection. The participant with HIV-1 RNA 1 680 000 copies/mL at screening/baseline was a 54-year-old white man with a CD4+ cell count of 8 cells/µL, CDC classification stage A, WHO clinical stage 1 (asymptomatic), and chronic infection. The participant with HIV-1 RNA 105 000 copies/mL at screening/baseline was a 28-year-old white man with a CD4+ cell count of 468 cells/µL, CDC classification stage A, WHO clinical stage 1 (asymptomatic), and early infection. The participant with HIV-1 RNA 92 900 copies/mL at screening/baseline was a 63-year-old black/African American woman with a CD4+ cell count of 127 cells/µL, CDC classification stage B, WHO clinical stage 2 (mild symptoms), and chronic infection. Abbreviations: CI, confidence interval; FDA, Food and Drug Administration; HIV-1, human immunodeficiency virus type 1; ITT, intent to treat; VL, viral load.

Figure 2.

Virologic response over time since darunavir/cobicistat/emtricitabine/tenofovir alafenamide rapid initiation (human immunodeficiency virus type 1 RNA

Figure 3.

Human Immunodeficiency Virus Treatment Satisfaction Questionnaire status version (HIVTSQs) scores at weeks 4, 24, and 48 after rapid initiation of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. A, Total HIVTSQs scores. B, HIVTSQs subscale scores. aHigher scores indicate greater satisfaction. Abbreviation: SE, standard error.