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HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial.
- Source :
-
Journal of the International AIDS Society [J Int AIDS Soc] 2021 Nov; Vol. 24 (11), pp. e25833. - Publication Year :
- 2021
-
Abstract
- Introduction: A potential concern with the use of dapivirine (DPV) for HIV prevention is the selection of a drug-resistant virus that could spread and reduce the effectiveness of non-nucleoside reverse transcriptase (NNRTI)-based first-line antiretroviral therapy. We evaluated HIV-1 seroconversions in MTN-020/ASPIRE for selection of drug resistance and evaluated the genetic basis for observed reductions in susceptibility to DPV.<br />Methods: MTN-020/ASPIRE was a placebo-controlled, Phase III safety and effectiveness study of DPV ring for HIV-1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda between 2012 and 2015. Plasma from individuals who seroconverted in ASPIRE was analysed for HIV-1 drug resistance using both population Sanger sequencing and next-generation sequencing (NGS) with unique molecular identifiers to report mutations at ≥1% frequency. DPV susceptibility of plasma-derived recombinant HIV-1 containing bulk-cloned full-length reverse transcriptase sequences from MTN-020/ASPIRE seroconversions was determined in TZM-bl cells. Statistical significance was calculated using the Fisher's exact test.<br />Results: Plasma from all 168 HIV seroconversions were successfully tested by Sanger sequencing; 57 of 71 DPV arm and 82 of 97 placebo (PLB) arm participants had NGS results at 1% sensitivity. Overall, 18/168 (11%) had NNRTI mutations including K101E, K103N/S, V106M, V108I, E138A/G, V179D/I/T and H221Y. Five samples from both arms had low-frequency NNRTI mutations that were not detected by Sanger sequencing. The frequency of NNRTI mutations from the DPV arm (11%) was not different from the PLB arm (10%; p = 0.80). The E138A mutation was detected in both the DPV (3 of 71 [4.2%]) and PLB arm (5 of 97 [5.2%]) and conferred modest reductions in DPV susceptibility in some reverse transcriptase backgrounds but not others.<br />Conclusions: HIV-1 drug resistance including NNRTI resistance did not differ between the DPV and placebo arms of the MTN-020/ASPIRE study, indicating that drug resistance was not preferentially acquired or selected by the DPV ring and that the preventive benefit of DPV ring outweighs resistance risk.<br /> (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)
- Subjects :
- Drug Resistance, Viral genetics
HIV Reverse Transcriptase genetics
HIV Reverse Transcriptase pharmacology
HIV Reverse Transcriptase therapeutic use
Humans
Mutation
Pyrimidines
Reverse Transcriptase Inhibitors therapeutic use
Anti-HIV Agents pharmacology
Anti-HIV Agents therapeutic use
HIV Infections drug therapy
HIV Seropositivity drug therapy
HIV-1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1758-2652
- Volume :
- 24
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of the International AIDS Society
- Publication Type :
- Academic Journal
- Accession number :
- 34762770
- Full Text :
- https://doi.org/10.1002/jia2.25833