Strength in Amalgamation: Newer Combination Agents for HIV and Implications for Practice

Abstract

Antiretroviral (ART) therapy for the treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single-tablet regimens (STRs), including newer fixed-dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug-drug interactions. Newer STRs include dolutegravir (DTG)/lamivudine (3TC)/abacavir (ABC) (Triumeq; Viiv Healthcare, Research Triangle Park, NC), rilpivirine (RPV)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (Odefsey; Gilead, Foster City, CA), RPV/FTC/tenofovir disoproxil fumarate (TDF) (Complera; Gilead), elvitegravir (EVG)/cobicistat (COBI)/FTC/TDF (Stribild; Gilead), and EVG/COBI/FTC/TAF (Genvoya; Gilead). Recently approved FDCs, such as atazanavir (ATV)/COBI (Evotaz; Bristol-Myers Squibb, Princeton, NJ), darunavir (DRV)/COBI (Prezcobix; Janssen Products, Titusville NJ), and FTC/TAF (Descovy; Gilead), are also now available. The Department of Health and Human Services treatment guidelines for HIV recommend many of these integrase strand transfer inhibitor (INSTI) STRs as a preferred choice for initiation of treatment in both ART-naive and -experienced patients because they offer comparably faster rates of virologic suppression, reduced rates of resistance development (especially with DTG), and overall better adherence than protease inhibitors or NNRTIs. Numerous phase 3 clinical trials support these recommendations including several switch or simplification clinical trials. Notably, the novel pharmacokinetic booster COBI, with its water soluble properties, has enabled the development and coformulation of a few of these STRs and FDCs. Also, a newer tenofovir salt formulation, TAF, has an advantageous pharmacokinetic profile, contributing to better overall renal and bone tolerability compared with TDF. Further simplification regimens comprising dual ART therapies are currently being explored. This review provides an overview of the clinical efficacy and safety data for these coformulated agents, highlighting the relative impact on comparative adverse events, assessing the potential for experiencing fewer drug-drug interactions, and discussing the clinical implications regarding adherence to treatment.

Keywords: adherence; antiretrovirals; combination therapy; drug interactions; fixed dose; human immunodeficiency virus; integrase; nonnucleoside; nucleoside; pill burden; protease; single-tablet regimen.