Browsing by Author "Frenkel LM"

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    Association of Virologic Failure and Nonnucleoside Reverse Transcriptase Inhibitor Resistance Found in Antiretroviral-Naive Children Infected With Human Immunodeficiency Virus and Given Efavirenz-Based Treatment.
    (2020-Apr-30) Higa N; Pelz A; Birch D; Beck IA; Sils T; Samson P; Bwakura-Dangarembizi M; Bolton-Moore C; Capparelli E; Chadwick E; Frenkel LM; University of California, San Diego, La Jolla.; University of Alabama at Birmingham, Alabama.; Centre for Infectious Disease Research in Zambia, Lusaka.; University of Washington, Seattle.; University of Zimbabwe College of Health Sciences, Harare.; Seattle Children's Research Institute, Washington.; Harvard T. H. Chan School of Public Health, Boston, Massachusetts.; Northwestern University Feinberg School of Medicine, Chicago, Illinois.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Among 66 antiretroviral-naive children aged <3 years with human immunodeficiency virus (HIV) or coinfected with HIV and tuberculosis and initiating efavirenz-based antiretroviral therapy (ART), non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected before ART in 5 (7.6%). Virologic failure occurred in 2 of these children; they were last tested at 16 and 24 weeks of ART. Pre-ART NNRTI resistance was not associated with virologic failure.
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    Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.
    (2009-Nov) Chi BH; Ellis GM; Chintu N; Cantrell RA; Sinkala M; Aldrovandi GM; Warrier R; Mbewe F; Nakamura K; Stringer EM; Frenkel LM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of <25-50%. We conducted a randomized trial of single-dose TDF/FTC added to peripartum nevirapine to reduce drug resistance associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs). To detect mutations for NNRTIs comprising > or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.