OBJECTIVES: To compare durability of antiretroviral therapy (ART) regimens among heavily treatment-experienced (HTE) people living with HIV (PLWH) and non-HTE treatment-experienced PLWH in care in the United States.

METHODS: ART-experienced PLWH in care in the OPERA Cohort on 12/31/2016 were identified as HTE (defined as being on a regimen indicative of HTE or experienced ≥3 core agent classes prior to current regimen) or non-HTE treatment experienced (not meeting the definition of HTE and on a three-drug regimen of 1 core agent and 2 nucleoside reverse transcriptase inhibitors (NRTIs)). Core agents were ART medications in classes other than NRTI. Regimens indicative of HTE included: twice-daily dolutegravir, twice-daily darunavir, etravirine, maraviroc, enfuvirtide, or integrase inhibitor+ protease inhibitor. Baseline was the start of the regimen taken on 12/31/2016; study end was 12/31/2018. Differences in time to regimen modification (defined as switching, discontinuing, or adding core agents) were compared using Kaplan-Meier methods.

RESULTS: HTE PLWH (n=2,277) were more likely to experience regimen modifications than non-HTE PLWH (n=21,906) (HTE: 45.3%, non-HTE: 41.3%; p=0.0002), but HTE had longer times to first modification [median 27.2 months (IQR: 16.6, 46.4)] than non-HTE [23.0 months (IQR: 14.4, 33.8); log-rank p<0.0001]. Among HTE PLWH, modifications to regimens containing ≥2 core agents occurred most frequently (58.4%). Modifications were more likely single core agent switches among non-HTE, including switches within the same ART class (non-HTE: 22.7%, HTE: 4.8%; p<0.0001) or between different classes (non-HTE: 35.8%, HTE: 7.8%; p<0.0001). HTE PLWH were less likely to experience treatment gaps of >45 days (HTE: 20.7%, non-HTE: 33.4%; p<0.0001).

CONCLUSIONS: HTE PLWH often require complex, highly-tailored ART regimens due to decreased effectiveness and tolerability of multiple ART classes developed over long-term ART exposure. In this analysis, baseline regimens were less durable among HTE PLWH, with more frequent and complex regimen modifications needed compared to non-HTE PLWH.