1011 - Efficacy and Safety of Doravirine in Treatment-Naïve Adults ≥50 Years Old With HIV-1

Background: Nearly 50% of people living with HIV in the US are ≥50 years old. Older people are more likely to have late-stage HIV infection at diagnosis, greater risk for cardiovascular disease and certain cancers, and concurrent medications for common age-related conditions. Doravirine (DOR) is a next-generation NNRTI with activity against first-generation NNRTI-associated mutations, a neutral impact on lipids, and few drug-drug interactions with commonly used medications.

Methods: We compared Week 96 results from DOR Phase 2 and Phase 3 trials (P007, P018, and P021) in treatment-naïve adults ≥50 vs < 50 years old. 855 participants received DOR 100mg +2 NRTIs in P007 & P018 or fixed combination DOR/3TC/TDF in P021; 383 participants received ritonavir-boosted darunavir (DRV) +2 NRTIs in P018; and 472 received efavirenz (EFV) 600mg +FTC/TDF in P007 or fixed combination EFV/FTC/TDF in P021. Participants who took ≥1 dose of study drug were included; the Observed Failure approach was used for missing efficacy data. All analyses were done by descriptive statistics.

Results: Of 1710 participants, 187 (11%) were 50-70 (median 54) years old at study entry. Baseline characteristics and treatment outcomes are summarized below for participants < 50 vs ≥50 years old. The older cohort had more women, more participants with AIDS, and lower median CD4+ T-cell counts than the younger cohort, whereas baseline HIV-1 RNA was similar between age cohorts. Hypertension and use of analgesics were more common in older participants. In each treatment group, the older cohort had a higher proportion of participants with HIV-1 RNA< 50 copies/mL at week 96 and fewer discontinuations due to lack of efficacy than the younger cohort. Mean change in CD4+ T-cell count was similar between age cohorts in the DOR and DRV groups and was lower for older participants in the EFV group. Rates of drug-related AEs and serious drug-related AEs were similar between age cohorts across all treatment groups. Discontinuations due to drug-related AEs were similar between age cohorts in the DOR group and were slightly higher for older participants in the DRV and EFV groups.

Conclusion: DOR is a beneficial option for adults ≥50 years old, given its similar efficacy and favorable safety profile compared to younger adults. Doravirine Phase 2 and Phase 3 Trials in Treatment-Naïve Adults