HIV Drug Resistance Assessment among Women who Seroconverted during the MTN-025/HOPE Open-Label Extension Dapivirine Vaginal Ring Trial.

Abstract

BACKGROUND:

Clinical trials of dapivirine vaginal ring have shown it is safe, effective, and desired by women as an HIV prevention option. The risk of drug resistance is a potential concern for dapivirine ring users who acquire HIV. We conducted a comprehensive resistance evaluation of plasma samples from the women who seroconverted during the Microbicide Trials Network (MTN)-025/HOPE open-label study of dapivirine ring.

METHODS:

Plasma collected on the visit at which seroconversion was detected was tested by next-generation sequencing with unique molecular identifiers (NGS-UMI) for non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations (DRM) present at ≥1% frequency. Bulk-cloned plasma-derived recombinant HIV was phenotyped in a TZM-bl-based assay for susceptibility to dapivirine and other NNRTI. HIV-1 RNA was retrospectively quantified in plasma samples collected prior to HIV seroconversion.

RESULTS:

Among 38 participants who seroconverted in HOPE, 7 (18%) had NNRTI DRM detected by NGS-UMI including A98G, K103N, V106M, E138A and V179D. Six of 7 samples with NNRTI DRM had <3-fold reduction in susceptibility to dapivirine. Only one sample with K103N and a V179I polymorphism had 9-fold reduction in susceptibility to dapivirine, but this genotype occurred in an individual who did not use dapivirine ring, likely indicating transmitted resistance. Detection of NNRTI resistance was not higher in individuals who remained on dapivirine ring >3 months after acquiring HIV infection.

CONCLUSION:

NNRTI resistance among women who seroconverted during HOPE was infrequent and selection of dapivirine-specific mutations was not detected. Dapivirine ring is considered a safe and effective option for HIV prevention in women.

• Authors: Urvi M Parikh, Kerri J Penrose, Amy L Heaps, Rahil Sethi, B Jay Goetz, Daniel Szydlo, Uma Chandran, Thesla Palanee-Phillips, Nyaradzo M Mgodi, Jared M Baeten, John W Mellors, and the MTN-025/HOPE Study Team
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) (Sep 20 2023) ISSN: 1944-7884 [Electronic] United States
• PMID: 37732881 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.