DORA : 48-week weight and metabolic changes in Black women with HIV, in a phase IIIb switch study from dolutegravir- or efavirenz- to doravirine-based first-line antiretroviral therapy

DATA AVAILABILITY STATEMENT The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Requests for access to the DORA study data should be sent to [email protected]. De-identified participant data and a data dictionary can be made available and shared under a data transfer agreement.OBJECTIVES : Treatment-related weight gain and metabolic complications with antiretroviral integrase-based regimens, especially among Black women, suggest the need for alternative options. METHODS : We conducted a 48-week, open-label, single-arm, single-centre, phase IIIb switch study to evaluate the tolerability, safety and efficacy of switching from stable efavirenz- or dolutegravir-based antiretroviral therapy to doravirine/lamivudine/tenofovir disoproxil fumarate in Black women. RESULTS : The 101 participants enrolled (median age 35 years; interquartile range 31–40) were on efavirenz (n = 46; mean duration on therapy 1.7 years) or dolutegravir-based (n = 55; mean duration 1.5 years) antiretrovirals at screening. Retention at 48 weeks was 92/101 participants, and viral suppression was >90% throughout the study, with a single case of doravirine resistance (106 M, V108I and H221Y mutations). The mean weight percentage change at week 48 was 4.7% (95% confidence interval [CI] 3.0–6.5; p < 0.001), and the adjusted mean change was 2.7 kg (95% CI 1.50–3.98; p < 0.001); for efavirenz, the percentage change was 5.0% (95% CI 2.9–7.1; p < 0.001), and the adjusted weight gain was 3.5 kg (95% CI 1.93–5.13); for dolutegravir, the percentage change was 4.5% (95% CI 1.8–7.3; p < 0.001), and the adjusted weight gain was 2.1 kg (95% CI 0.26–3.90). Statistically significant decreases in lipid panel percent mean to week 48 included: total cholesterol −8.4% (95% CI −11.3 to −5.5; p < 0.001), triglycerides −10.4% (95% CI −16.4 to −4.4; p < 0.001) and high-density lipoprotein −14.8% (95% CI −18.5 to −11.2%; p < 0.001), with minor differences when disaggregating the mean percent change in lipids between previous efavirenz/dolutegravir regimens. Adverse events due to doravirine were few and mild. CONCLUSIONS : Our findings suggest that a switch to doravirine from efavirenz or dolutegravir is safe and effective in Black women, with significant improvement in lipid profiles, but does not arrest progressive weight gain.MSD Sharp and Dohme.http://wileyonlinelibrary.com/journal/hivhj2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein