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

Abstract

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.

Keywords:

• HIV-1
• acute HIV-1 infection
• early HIV-1 infection
• rapid initiation
• darunavir

Acknowledgments

Medical writing support was provided by Caryn Gordon, PharmD, and Courtney St. Amour, PhD, of MedErgy.

Disclosure statement

This study was supported by Janssen Scientific Affairs, which was involved in the study design, analysis and interpretation of results, manuscript preparation, and publication decisions. K. Dunn, R. Rogers, R.B. Simonson, P.T. Kassam, and S. Seyedkazemi are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson. D. Luo, S. Sheng, and H. Hardy are employees of Janssen Research & Development, LLC; D. Luo and H. Hardy are stockholders of Johnson & Johnson.

Data availability statement

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

Additional information

Funding

This work was funded by Janssen Scientific Affairs, LLC.

Notes on contributors

Keith Dunn

Keith Dunn, PharmD, BCPS, AAHIVE is Scientific Field Director, Infectious Diseases for Janssen Infectious Diseases & Vaccines. Dr. Dunn earned his PharmD at Northeastern University. He began caring for people living with HIV in 2008 through a 2-year residency in HIV at Boston University, which cared for >1,000 people living with HIV. As a Scientific Field Director at Janssen, he addresses data gaps identified by the HIV community and how novel treatment options for people living with HIV may meet patients’ needs. Most recently Keith has focused his research efforts to better understand the efficacy and safety of starting patients on ART rapidly, the cost implications of delaying treatment, and newly emergent CNS and metabolic concerns with ART.

Rachel Rogers

Rachel Rogers, PharmD, is an Associate Medical Director for Janssen Infectious Diseases & Vaccines. She has served in other roles across the Janssen Infectious Diseases & Vaccines franchise to support research, launch activities, and business partner collaborations. She received her PharmD at Rutgers University and completed post-graduate training at Duke University Hospital and an Infectious Diseases specialty residency at the South Texas Veterans Affairs (VA) Healthcare System. She remained at the VA in HIV/HCV clinical practice prior to joining Janssen.

Richard Bruce Simonson

Richard Bruce Simonson is a Director for Janssen Infectious Diseases & Vaccines. He has served other roles within Janssen across Infectious Diseases and other therapeutic areas; in these roles he has managed multiple phase 3 and phase 4 clinical trials.

Donghan Luo

Donghan Luo is an experienced statistician with over 20 years of clinical research experience in the pharmaceutical industry. He has authored and published over 30 clinical research manuscripts in the areas of infectious disease, diabetes, oncology, and cardiovascular disease. He had academic training in mathematics and statistics, with a PhD in Mathematics and MS in Biometrics and Statistics.

Shubin Sheng

Shubin Sheng, PhD, is Associate Director, Biostatistics at Cytel FSP-Janssen. He has more than 13 years of experience as a biostatistician in clinical trials and outcomes research. Prior to joining Cytel, he served as a Biostatistician III at Duke Clinical Research Institute (DCRI). He attended the University of Illinois at Urbana Champaign and received a PhD in Molecular Physiology and MS in Statistics.

Purnima T. Kassam

Purnima T. Kassam, PharmD, is an Associate Field Director, MSLs supporting the Janssen Infectious Diseases & Vaccines team. She earned her PharmD from the University of the Sciences in Philadelphia in 2005. In her current role in Medical Affairs, she supports healthcare professionals by addressing medical inquiries, collaborating with business partners, and supporting efforts in HIV clinical research.

Sareh Seyedkazemi

Sareh Seyedkazemi, PharmD, is Director of Scientific Communications at Janssen Infectious Diseases & Vaccines. In this role she is predominantly responsible for leading a team delivering on data dissemination efforts. She earned her PharmD degree from the University of Maryland, Baltimore and completed a PGY-1 residency at Mercy Hospital in Miami, FL. She joined Janssen Infectious Diseases & Vaccines in 2015.

Hélène Hardy

Hélène Hardy is a Senior Director in R&D at Janssen Pharmaceuticals. She serves as a Compound Development Team Leader at Janssen Research & Development, Pharmaceutical Companies of Johnson & Johnson in the Infectious Diseases & Vaccines therapeutic area. Her current research focuses on bacteriophage therapy, and she has been active in HIV drug development since 2010 via the tenure of various roles within the pharmaceutical industry.