Minority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan women
Internal Medicine (East Africa)
Objectives: Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure
Design/methods: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure.
Results:Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all P
Conclusion: Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.
Publication ( Name of Journal)
Milne, R. S.,
Silverman, R. A.,
Beck, I. A.,
Sibley, T. R.,
Kiarie, J. N.,
Sakr, S. R.,
(2019). Minority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan women. AIDS, 33(6), 941-951.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_intern_med/143