Durability of Two-Drug Antiretroviral Regimens as Maintenance Therapy in People Living with HIV and Reasons for Switch to a Three-Drug Regimen: A Real-Life Cohort Study

Use of two-drug regimens (2DR) can reduce lifetime exposure to antiretroviral drugs while maintaining viral suppression. We aim to assess the real-life durability of 2DR in treatment-experienced people living with HIV (PLWH) who are virologically suppressed. We conducted a monocentric retrospective study in a referral center for PLWH in Northern France. PLWH who received 2DR as maintenance therapy (viral load <50 copies/mL at initiation) anytime between 1 January 2011 and 1 May 2023 were included. The duration of 2DR, reasons for and factors associated with switching to 3DR were analyzed. A total of 579 PLHIV were included. Dolutegravir (DTG) or ritonavir-boosted protease inhibitor (PI/r)-based 2DR were the most frequently prescribed regimens, respectively, in 64% and 16% of cases. Sixty-nine patients (12%) received injectable long-acting cabotegravir-rilpivirine. Reasons for initiating 2DR were mainly drug reduction (61%). Median follow-up time on 2DR was 20.4 months (IQR: 7.9-36.4) with 110 patients (19%) switching to 3DR after a median duration of 10.1 months (IQR: 2.7-26.5). Sixteen patients returned to a 3DR because of virological failure leading to one new onset of resistance-associated mutation. 2DR durability was significantly longer with the DTG-based regimen (<i>p</i> < 0.0001). History of CD4⁺ T cell count <200/mm3 (HR: 1.64, 95% CI: [1.09-2.47], <i>p</i> = 0.018) and number of previous antiretroviral regimen (HR: 1.92, 95% CI: [1.74-2.12], <i>p</i> < 0.001) were associated with a return to a 3DR. Our study showed that 2DR was a sustainable simplification strategy in a real-life setting. The return to 3DR was significantly impacted by the prescription of 2DR in patients heavily pre-treated.