Drug-sparing regimens have the potential to reduce complexity, toxicity, and cost of antiretroviral therapy (ART). Our objectives were to describe two-drug regimen (2-DR) use among ART-experienced HIV+ patients in a large clinical cohort, and to compare virologic outcomes of 2-DRs and three-drug regimens (3-DRs) following switch during the study period.
Between 1/1/2010 and 6/30/2016, ART-experienced patients starting a new 2-DR or 3-DR, were selected from the OPERA cohort. Patients were observed from regimen start date (baseline) until regimen discontinuation (d/c), loss to follow-up, death, or study end (6/30/2017). Outcomes were stratified by viral load (VL) at baseline (switched while viremic: ≥50 copies/mL; stable switch: <50 copies/mL). Suppression during follow-up was defined as a VL <50 copies/mL; failure following suppression was defined as 2 consecutive VLs >200 copies/mL or a VL>200 copies/mL + d/c. Cox models for each outcome were fit to estimate adjusted hazard ratios (aHRs).
We identified 10,190 ART-experienced patients who switched during the study period; 1,337 (13%) switched to a 2-DR, and 8,853 (87%) to a 3-DR. At baseline, 2-DR patients were older, more likely to have AIDS, had been on ART longer and experienced more treatment lines, had more comorbidities, and were less likely to be a stable switch compared to 3-DRs (p<0.0001). The most common 2-DRs (55%) comprised a protease inhibitor and an integrase strand transfer inhibitor combination, regardless of baseline VL. Among those switching while viremic (2-DR: 612 (15%), 3-DR: 3566 (85%)), suppression during follow-up was comparable among patients on 2-DRs (61%) and 3-DRs (67%; aHR 1.00, 95% CI 0.88, 1.13) [Figure]. After achieving suppression during follow-up, 13% of 2-DR and 15% of 3-DR patients went on to experience a failure event. Among stable switch patients (2-DR: 723 (12%), 3-DR: 5285 (88%)), the difference in risk of virologic failure during follow-up was not statistically significant between 2-DR and 3-DR patients (10% vs. 11%; aHR 1.15, 95% CI 0.90, 1.48) [Figure].
Virologic outcomes were comparable between ART-experienced patients switching to two- and three-drug regimens, regardless of whether patients were virologically controlled at switch. These findings support the continued evaluation of 2-DRs in clinical trials and real-world settings. Long-term outcomes require further assessment.