Characterization of Viruses in Phase 3 and Phase 3b Trials (the Ring Study and the Dapivirine Ring Extended Access and Monitoring Trial) of the Dapivirine Vaginal Ring for Human Immunodeficiency Virus Type 1 Infection Risk Reduction.
Clin Infect Dis
; 76(6): 996-1002, 2023 03 21.
Article
en En
| MEDLINE
| ID: mdl-36345569
ABSTRACT
BACKGROUND:
The Ring Study demonstrated 35.1% human immunodeficiency virus type 1 (HIV-1) infection risk reduction among participants who used the Dapivirine vaginal ring-004 (DVR), whereas the Dapivirine Ring Extended Access and Monitoring (DREAM) trial, approximated a 62% risk reduction. The observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) and effects on viral susceptibility are described here.METHODS:
Population-based genotyping on plasma samples collected longitudinally, and next-generation sequencing (NGS) and phenotypic susceptibility testing were done on plasma collected at seroconversion. Retrospective HIV-1 RNA testing was used to more accurately establish the time of infection.RESULTS:
In the Ring Study, NNRTI RAMs were not observed in most viruses at seroconversion (population-based genotyping DVR 71 of 84, 84.5%; placebo 50 of 58, 86.2%). However, more E138A was found in the DVR group (E138A DVR 9 of 84, 10.7%; placebo 2 of 58, 3.4%; P = .2, Fisher exact test). NGS detected 1 additional mutation in each group (DVR G190A; placebo G190A and G190E). Marginal dapivirine susceptibility reduction was found with NNRTI RAMs at seroconversion (geometric mean fold-change, range DVR, 3.1, 1.3-5.1; placebo, 5.8, 0.9-120). NNRTI RAMs were not emergent between first detectable HIV-1 RNA and seroconversion when these visits differed (paired samples, mean ring use DVR, n = 52, 35 days; placebo, n = 26, 31 days). After stopping DVR, 2 of 63 viruses had emergent G190G/A or K103K/N with V106V/M at final study visit. Resistance profiles from the DREAM trial were consistent with the Ring Study.CONCLUSIONS:
DVR showed little potential for selection of NNRTI-resistant variants. CLINICAL TRIALS REGISTRATION NCT01539226 and NCT02862171.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
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VIH-1
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Seropositividad para VIH
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Dispositivos Anticonceptivos Femeninos
/
Fármacos Anti-VIH
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Clin Infect Dis
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
Año:
2023
Tipo del documento:
Article
País de afiliación:
Sudáfrica