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.

Keywords: ART; HIV-1; NNRTIs; doravirine; inflammation; metabolic profile.

Fig 1

(A) Virologic control (HIV-RNA <50 copies/mL), virologic failure (HIV-RNA ≥50 copies/mL), and missing virologic data at week 24 (w24) and week 48 (w48). M = F : missing equal failure – intention-to-treat analysis; M = E : missing equal excluded – per-protocol analysis. The figure shows bars for both the intention-to-treat analysis considering missing as failure (w24 in pale green and w48 in pale blue), and the per-protocol analysis treating missing as excluded (w24 in dark green and w48 in dark blue). (B) Virologic outcomes at w48 and w96 according to FDA guidelines; confidence intervals are shown in parentheses. *Other reasons include subjects who discontinued study drugs due to the investigator’s discretion, subject decision, loss to follow-up, noncompliance with the study drug, protocol violation, and pregnancy.

Fig 2

Metabolic and inflammatory changes over time. The bars show the median percentage relative difference from baseline (BL) for the metabolic parameters considered at both week 24 (w24) and week 48 (w48). The P-value shown upon each bar comes from the paired Wilcoxon test between BL and the considered time-point. Vertical lines show the interquartile range. (A) Metabolic profile. (B) Inflammatory profile. IL-6: interleukin 6; hs-PCR: high-sensitivity C-reactive protein; TC: total cholesterol; TC/HDL: total cholesterol/HDL cholesterol ratio.