Doravirine 100mg tablets

Abstract Background Doravirine/islatravir is an investigational regimen that is being studied for human immunodeficiency virus type 1 (HIV-1) treatment. Methods In this phase 3, double-blind, double-dummy trial (ClinicalTrials.gov NCT04233879), previously untreated adults with HIV-1 were randomized (1:1) and stratified by HIV-1 RNA (≤/>100 000 copies/mL) and CD4 count (</≥200 cells/µL) to doravirine/islatravir (100/0.75 mg) or bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) orally once-daily (primary endpoint: percentage of participants with HIV-1 RNA <50 copies/mL at week 48; US Food and Drug Administration snapshot, 10% noninferiority margin). Results Overall, 597 participants were treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. Doravirine/islatravir was noninferior to bictegravir/emtricitabine/tenofovir alafenamide: 265 of 298 (88.9%) versus 264 of 299 (88.3%) had HIV-1 RNA <50 copies/mL (difference, 0.5%; 95% confidence interval [CI]: −4.7, 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference, −50; 95% CI: −79, −21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 × 109/L (difference, −0.20; 95% CI: −0.30, −0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with coronavirus disease 2019 being most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs that led to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria that required discontinuation for decreased CD4 and lymphocyte counts. Conclusions Doravirine/islatravir (100/0.75 mg) once-daily was noninferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped. Clinical Trials Registration NCT04233879.

Abstract licence: CC BY-NC-ND

OBJECTIVE: To evaluate changes in weight and BMI in adults with HIV-1 at 1 and 2 years after starting an antiretroviral regimen that included doravirine, ritonavir-boosted darunavir, or efavirenz. DESIGN: Post-hoc analysis of pooled data from three randomized controlled trials. METHODS: We evaluated weight change from baseline, weight gain at least 10%, and increase in BMI after 48 and 96 weeks of treatment with doravirine, ritonavir-boosted darunavir, or efavirenz-based regimens. Risk factors for weight gain and metabolic outcomes associated with weight gain were also examined. RESULTS: Mean (and median) weight changes were similar for doravirine [1.7 (1.0) kg] and ritonavir-boosted darunavir [1.4 (0.6) kg] and were lower for efavirenz [0.6 (0.0) kg] at week 48 but were similar across all treatment groups at week 96 [2.4 (1.5), 1.8 (0.7), and 1.6 (1.0) kg, respectively]. No significant differences between treatment groups were found in the proportion of participants with at least 10% weight gain or the proportion with BMI class increase at either time point. Low CD4 T-cell count and high HIV-1 RNA at baseline were associated with at least 10% weight gain and BMI class increase at both timepoints, but treatment group, age, sex, and race were not. CONCLUSION: Weight gains over 96 weeks were low in all treatment groups and were similar to the average yearly change in adults without HIV-1. Significant weight gain and BMI class increase were similar across the treatment groups and were predicted by low baseline CD4 T-cell count and high baseline HIV-1 RNA.

Abstract licence: CC BY-NC-ND 4.0