Browsing by Author "Dross, Sandra"

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    Increasing HIV-1 pretreatment drug resistance among antiretroviral-naive adults initiating treatment between 2006 and 2014 in Nairobi, Kenya
    Chung, Michael H.; Silverman, Rachel A.; Beck, Ingrid A.; Yatich, Nelly; Dross, Sandra; McKernan-Mullin, Jennifer; Bii, Stephen; Tapia, Kenneth; Stern, Joshua A.; Chohan, Bhavna; Sakr, Samah R.; Kiarie, James N.; Frenkel, Lisa M. (Lippincott Williams & Wilkins, 2016-06-19)
    Antiretroviral-naïve adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. Prevalence of pretreatment drug resistance increased from 3.89% in 2006 to 10.93% in 2014 (P < 0.001), and 95% of those with resistance had at least one nonnucleoside reverse transcriptase inhibitor mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006.
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    Minority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan women
    Milne, Ross S.; Silverman, Rachel A.; Beck, Ingrid A.; McKernan-Mullin, Jennifer; Deng, Wenjie; Sibley, Thomas R.; Dross, Sandra; Kiarie, James N.; Sakr, Samah R.; Coombs, Robert W.; Chung, Michael H.; Frenkel, Lisa M. (Lippincott Williams & Wilkins, 2019-05-01)
    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 < 0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing. 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.