Doravirine therapy for HIV safe, maintains long-term virologic suppression

Doravirine as first-line therapy for HIV infection is well tolerated and effectively maintains long-term virologic suppression in adult patients, according to study results published in The Lancet HIV.

Researchers conducted an open-label extension study of 2 multicenter, double-blind, randomized, active comparator-controlled phase 3 trials (ClinicalTrials.gov Identifiers: NCT02275780 and NCT02403674). Both trials were designed to assess the efficacy and safety of doravirine through 96 weeks among adult patients with HIV infection who were naive to antiretroviral therapy. Patients in the first trial received either doravirine or ritonavir-booted darunavir in combination with 2 nucleos(t)ide reverse transcriptase inhibitors once daily. Patients in the second trial received fixed-dose combinations of either doravirine plus lamivudine and tenofovir disoproxil fumarate or efavirenz plus emtricitabine and tenofovir disoproxil fumarate. Results captured in both trials showed noninferior antiviral efficacy between the comparator groups.

In this extension study, the researchers assessed 192-week efficacy and safety outcomes among patients who were eligible to either continue doravirine or switch from a comparator (boosted darunavir or efavirenz) to doravirine for an additional 96 weeks. Outcomes were also assessed among patients who were randomly assigned to receive doravirine at day 1 and continued therapy through 196 weeks (n=747; doravirine cumulative group).

A total of 550 patients (mean [SD] age, 34.6 [10.5] years; 83% men) continued doravirine and 502 (mean age, 34.0 [10.4] years; 86% men) switched to doravirine in the extension trial.

At 192 weeks, virologic suppression was maintained among 83% of patients who continued doravirine and 80% of those who switched to doravirine. Of patients in the doravirine cumulative group with available data at this time (n=457), virologic suppression was maintained in 79%.

The researchers noted virologic failure among 11% of patients in the cumulative doravirine group, primarily occurring in the first 48 weeks of treatment.

In regard safety, adverse events (AEs) reported by more than 10% of patients in any group included diarrhea, nasopharyngitis, headache, upper respiratory tract infection, and nausea. Severe treatment-related AEs were reported by 38 (7%) patients who continued doravirine, 37 (7%) who switched to doravirine, and 17 (2%) of those in doravirine cumulative group.

Overall, 3 patients who continued doravirine and 1 who switched to doravirine discontinued therapy due to treatment-related AEs. Patients who discontinued therapy experienced angioedema, osteopenia, insomnia, and increased levels of alanine aminotransferase and aspartate aminotransferase.

Limitations of this study include the use of pooled data from 2 previous trials, the predominance of younger White men, and the under-representation of patients from racial and ethnic minority groups.

According to the researchers, “These results support the long-term efficacy, safety, durability, and overall therapeutic benefit of doravirine-based regimens.”

Disclosures: This research was supported by Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Sophie Wei

References:

Orkin C, Molino JM, Cahn P, et al; on behalf of DRIVE-FORWARD and DRIVE-AHEAD collaborators. Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials. Lancet HIV. Published online December 20, 2023. doi:10.1016/S2352-3018(23)00258-8.