Clinical outcomes of two-drug regimens vs. three-drug regimens in antiretroviral treatment-experienced people living with HIV

Greenberg, Lauren; Ryom, Lene; Neesgaard, Bastian; Wandeler, Gilles; Staub, Therese; Gisinger, Martin; Skoll, Michael; Günthard, Huldrych F; Scherrer, Alexandra; Mussini, Cristina; Smith, Colette; Johnson, Margaret; De Wit, Stéphane; Necsoi, Coca; Pradier, Christian; Wit, Ferdinand; Lehmann, Clara; d’Arminio Monforte, Antonella; Miró, Jose M; Castagna, Antonella; ... (2021). Clinical outcomes of two-drug regimens vs. three-drug regimens in antiretroviral treatment-experienced people living with HIV. Clinical infectious diseases, 73(7), e2323-e2333. Oxford University Press 10.1093/cid/ciaa1878

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Background: Limited data exist comparing clinical outcomes of two-drug regimens (2DRs) and three-drug regimens (3DRs) in people living with HIV.

Methods: Antiretroviral treatment-experienced individuals in RESPOND switching to a new 2DR or 3DR from 1/1/12-1/10/18 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression.

Results: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median 52.6 years [interquartile range 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%).There were 619 events during 27,159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU [95% CI 20.7-24.5]) on 3DRs, 79 (30.9/1000 PYFU [24.8-38.5]) on 2DRs. The most common events were death (7.5/1000 PYFU [95% CI 6.5-8.6]) and non-AIDS cancer (5.8/1000 PYFU [4.9-6.8]). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio: 0.92 [0.72-1.19]; p=0.53).

Conclusions: This is the first large, international cohort assessing clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes; further research on resistance barriers and long-term durability of 2DRs is needed.

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