Efficacy, safety, and anti-inflammatory properties of the switch to a doravirine-based regimen among antiretroviral-experienced elderly people living with HIV-1: the DORAGE cohort.

Abstract

Doravirine (DOR) is a novel antiretroviral agent with a favorable resistance profile and high tolerability. However, evidence is limited on DOR among elderly people living with HIV (PLWH) and whether it might modulate chronic inflammation. We aimed to investigate the efficacy, safety, and tolerability of DOR as a switching strategy among elderly PLWH and its impact on chronic inflammation in a real-life setting. We recruited a cohort of ART-experienced PLWH undergoing a therapeutic switch to a DOR-based regimen under virologic control (defined as HIV-RNA <200 copies/mL), regardless of the previous ART regimen. The primary objective was the evaluation of the rate of virologic control at 48 weeks post-switch. Secondary objectives included analyzing immune and metabolic outcomes. Plasmatic hs-CRP, IL-6, and D-dimer levels were measured as chronic inflammation markers. Overall, 150 PLWH were screened, and 147 were enrolled into the study. A total of 134 PLWH completed the follow-up. The rate of virological control was 96.1% (122/134; CIs: 91.0%-98.7%) in the per-protocol analysis. After 48 weeks from the switch, we recorded significant reductions in serum fasting glycemia (P 0.019), triglycerides (P 0.024), and total cholesterol/HDL ratio (P 0.017); no clinically significant differences were detected in the body weight and BMI, as long as in immune, hepatic, and renal profiles. A significant reduction in IL-6 (P 0.019) and hs-CRP (P 0.019) was observed. DOR is an effective and safe treatment choice for elderly PLWH. The intriguing modulatory effect of DOR-based regimens on chronic systemic inflammation deserves further investigation.