Much progress has been made in the development of antiretroviral therapies (ARTs) for HIV-1 infection. Beginning a little over a decade ago, single tablet combination regimens (STRs) became available, and subsequently, newer STR formulations with improved safety profiles have emerged. Recently, there is a growing interest in regimen simplification with the primary goal of further reducing long-term toxicities of ART and improving medication adherence. Dolutegravir/rilpivirine (DTG/RPV) was approved by the US Food and Drug Administration (FDA) as the first dual antiretroviral STR for the maintenance therapy of HIV-1 infection. Following an extensive review of all published papers on RPV and DTG, administered alone and in combination, extracted from databases including PubMed, Google scholar, and EMBASE, as well as drug package inserts and conference abstracts and proceedings, this review discusses the chemical properties and composition, pharmacodynamics and pharmacokinetic properties, clinical trial efficacy and safety data, as well as important drug–drug interactions associated with DTG/RPV. An expert opinion section discusses ideal candidates for DTG/RPV in the context of available but limited data and in comparison to currently available and emerging ART alternatives.

There have been remarkable advances in drug development for the treatment of HIV-1 infection. From the co-formulation of combination antiretroviral therapy (cART) into single-tablet regimens to the development of long-acting antiretroviral (ARV) drug formulations, the treatment of HIV has and will become much more tolerable and less complicated for patients. In addition, and appropriately, there is a focus on reducing short- and long-term toxicities of treatment while maintaining robust efficacy. One of such approaches includes 2-drug regimen constructs that contain and retain effective ARV compounds while excluding components that have relatively unfavorable toxicity profiles. The first-ever 2-drug regimen approved for the treatment of HIV-1 infection for treatment-naive people living with HIV (PLWH), consisting of the integrase inhibitor dolutegravir (DTG) and the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine (3TC), is reviewed in this paper. The chemical composition and properties, pharmacokinetic and pharmacodynamics profile, and clinical trial data on efficacy and safety of DTG/3TC are presented. An expert opinion aims to highlight important considerations for the use of DTG/3TC in the context of existing and emerging ARV options.