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Review
. 2022 Dec;9(12):e868-e883.
doi: 10.1016/S2352-3018(22)00249-1. Epub 2022 Oct 26.

Two-drug regimens for HIV treatment

Kevin M Gibas  1 , Sean G Kelly  1 , Jose R Arribas  2 , Pedro Cahn  3 , Chloe Orkin  4 , Eric S Daar  5 , Paul E Sax  6 , Babafemi O Taiwo  7
Affiliations
Review

Two-drug regimens for HIV treatment

Kevin M Gibas et al. Lancet HIV. 2022 Dec.

Abstract

Combination therapy with three antiretroviral agents has been integral to successful HIV-1 treatment since 1996. Although the efficacy, adverse effects, and toxicities of contemporary three-drug regimens have improved, even the newest therapies have potential adverse effects. The use of two-drug regimens is one way to reduce lifetime exposure to antiretroviral drugs while maintaining the benefits of viral suppression. Multiple large, randomised trials have shown the virological non-inferiority of certain two-drug regimens versus three-drug comparators, including adverse effect differences that reflect known profiles of the antiretroviral drugs in the respective regimens. Two-drug combinations are now recommended in treatment guidelines and include the first long-acting antiretroviral regimen for the treatment of HIV-1. Recommended two-drug regimens differ in their risks for, and factors associated with, virological failure and emergent resistance. The tolerability, safety, metabolic profiles, and drug interactions of two-drug regimens also vary by the constituent drugs. No current two-drug regimen is recommended for people with chronic hepatitis B virus as none include tenofovir. Two-drug regimens have increased options for individualised care.

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Conflict of interest statement

Declaration of interests SGK has served on advisory boards for Gilead, ViiV, and Theratechnologies. JRA has received advisory fees, speaker fees, and grant support from ViiV, Janssen, Gilead, Merck, Aelix, and Thera. PC has worked on advisory boards at ViiV and Merck and received research and speaker funds from ViiV, CanSino, and Janssen and has received honoraria as a data safety and monitoring board member for Moderna. CO has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead, ViiV, Janssen, GlaxoSmithKline, AstraZeneca, and Merck. ESD has received research support from and is a consultant for Gilead, Merck, GlaxoSmithKline, and ViiV. PES receives research support from Gilead, GlaxoSmithKline, and ViiV. He serves as a scientific advisory board member and consultant for Gilead, GlaxoSmithKline, ViiV, Merck, and Janssen; and has editorial positions with UpToDate, Medscape, New England Journal of Medicine Journal Watch, and Open Forum Infectious Diseases. BOT has served as a consultant and received honoraria from GlaxoSmithKline, ViiV, Gilead, Merck, and Johnson & Johnson. KMG received a training grant from the Agency For Health Care Research and Quality (T32HS026122).

Figures

Figure:
Figure:. Timeline of two-drug antiretroviral therapy studies and guidelines
Two-drug regimens evaluated in each study: ATLAS-M: ritonavir-boosted atazanavir plus lamivudine;, GARDEL: ritonavir-boosted lopinavir plus lamivudine; NEAT 001/ANRS 143: ritonavir-boosted darunavir plus raltegravir; SALT: ritonavir-boosted atazanavir plus lamivudine;, OLE: ritonavir-boosted lopinavir plus lamivudine; LATTE-2: long-acting cabotegravir plus long-acting rilpivirine; DUAL-GESIDA 8014-RIS-EST45: ritonavir-boosted darunavir plus lamivudine; SWORD 1 and 2: dolutegravir plus rilpivirine;– GEMINI 1 and 2: dolutegravir plus lamivudine;, ATLAS: long-acting cabotegravir plus long-acting rilpivirine; FLAIR: long-acting cabotegravir plus long-acting rilpivirine;, PROBE-2: cobicistat-boosted darunavir plus rilpivirine; DUALIS: dolutegravir plus ritonavir-boosted darunavir; TANGO: dolutegravir plus lamivudine;, SALSA: dolutegravir plus lamivudine; DOLAM: dolutegravir plus lamivudine; ATLAS-2M: long-acting cabotegravir plus long-acting rilpivirine.– 3TC=lamivudine. bATV=boosted atazanavir. bDRV=boosted darunavir. bLPV=boosted lopinavir. bPI=boosted protease inhibitor. CAB=cabotegravir. DHHS=Department of Health and Human Services. DTG=dolutegravir. EACS=European AIDS Clinical Society. FTC=emtricitabine. IAS=International Antiviral Society. RAL=raltegravir. RPV=rilpivirine.
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