Two-drug regimens are shown to be comparable with 3-drug regimens as viable clinical treatment options for HIV, as demonstrated by the results of 2 studies presented at the virtual Conference on Retroviruses and Opportunistic Infections, held from March 8 to 11, 2020.1,2

Newer, more potent antiretrovirals have created an opportunity for effective therapy with fewer agents required, and several short-term studies have shown the virologic efficacy and tolerability of a 2-drug regimen.

Greenberg et al conducted a large, international cohort study to evaluate rigorously defined clinical outcomes on a 2-drug regimen.1 The study enrolled 9791 antiretroviral treatment (ART) -experienced people living with HIV (PLWHIV), of whom 11.1% were receiving a 2-drug regimen and 88.9% were receiving a 3-drug regimen.1 The individuals were followed from starting the first regimen of interest after cohort enrolment or January 1, 2012 (whichever occurred latest), until the first severe event of any type or until last clinical visit or January 10, 2018 (whichever occurred first).1

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Several clinical events were evaluated including cardiovascular disease, AIDS, non-AIDS-defining cancer, end-stage renal disease, end-stage liver disease, and death.1 dolutegravir + lamivudine (22.8%) and raltegravir + darunavir (19.85%) were the most common 2-drug regimens used in the study.1 Two nucleoside reverse transcriptase inhibitors + dolutegravir (46.9%) was the most common 3-drug regimen.1

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The median follow-up was 2.6 years and was similar for both treatment groups. In total, 619 clinical events took place during 27,159 person-years of follow-up (incidence rate/1000 person-years follow-up, 23.3; 95% CI, 21.6-25.2).1 Adjusting for potential confounders (demographic and clinical characteristics), the results revealed no significant difference in incidence rates of events between 2-drug regimens and 3-drug regimens (incidence rate ratio, 0.92; 95% CI, 0.72-1.19; P =.53).1

Limitations of the study included that residual confounding could not be ruled out and that analysis was only focused on a composite endpoint, and the inability to include treatment-naive individuals in the analysis.1

In a separate study conducted by Pierone et al, data were analyzed from the OPERA database of electronic health records from 105,643 PLWHIV in the United States and Puerto Rico who initiated either a 2-drug or a 3-drug regimen between January 2019 and December 2018.2 Study outcomes included virologic failure, sustained suppression, and treatment discontinuation. Patients were followed-up until regimen discontinuation, death, or study end (June 2019).2 Of note, patients who received a 2-drug regimen were older and were more likely to be Hispanic and to have comorbidities, whereas patients who received 3-drug regimens tended to be younger, to be African American, and to have a history of syphilis.2

The findings demonstrated that compared with patients who received a 3-drug regimen, those who received a 2-drug regimen experienced fewer discontinuations and were more likely to be suppressed at study end.2 Virologic failure was uncommon, and there were no differences between patients who used a 2-drug regimen and those who used a 3-drug regimen. Limitations of the study included the lack of data for reasons of discontinuation or resistance for those who failed.2 Overall, this real-world setting over the first 18 months of use demonstrates that there are no observed differences in risk for virologic failure between users of 2-drug regimens and users of 3-drug regimens.2

In summary, both studies support the hypothesis of the use of 2-drug regimens as a viable treatment strategy for PLWHIV.1,2 Further studies should investigate the long-term durability of 2-drug regimens.


1. Greenberg L, Ryom L, Neesgaard B, Wandeler G, Staub T, Skoll M, et al. Clinical outcomes of two drug regimens (2DRs) vs. three drug regimens (3DRs) in HIV. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA. Accessed March 19, 2020.

2. Pierone G, Schulman KL, Fusco J, Vannappagari V, Aboud M, van Wyk J, et al. 2-drug regimen comparable to 3-drug regimens up to 18 months in a real-world setting. Presented at: CROI 2020; March 8-11, 2020; Boston, MA. Accessed March 19, 2020.