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Pretreatment HIV drug resistance predicts accumulation of new mutations in ART‐naïve Ugandan children
Author(s) -
SoeriaAtmadja Sandra,
Amuge Pauline,
Nanzigu Sarah,
Bbuye Dickson,
Rubin Johanna,
Eriksen Jaran,
Kekitiinwa Adeodata,
Obua Celestino,
Gustafsson Lars L.,
Navér Lars
Publication year - 2020
Publication title -
acta paediatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/apa.15320
Subject(s) - efavirenz , medicine , viremia , drug resistance , hiv drug resistance , reverse transcriptase inhibitor , nucleoside reverse transcriptase inhibitor , prospective cohort study , viral load , cohort study , reverse transcriptase , virology , antiretroviral therapy , human immunodeficiency virus (hiv) , polymerase chain reaction , biology , biochemistry , gene , microbiology and biotechnology
Aim To assess the prevalence of pretreatment drug resistance (PDR) and its association with virologic outcomes after 24 weeks of antiretroviral therapy (ART), within an urban cohort of Ugandan children. Methods Prospective observational study. Baseline and 24‐week assessments of viral load (VL) and genotypic drug resistance to nucleoside reverse transcriptase inhibitors (NRTI) and non‐nucleoside reverse transcriptase inhibitors (NNRTI) were performed. Results Ninety‐nine ART‐naïve children (3‐12 years) initiated efavirenz‐based ART 2015‐2016 and 18/90 (20%) had baseline NRTI/NNRTI associated drug resistance mutations (DRMs). By 24 weeks, 72/93 (77%) children had VL < 40 copies/mL and a total of 23 children had DRMs. Children with PDR accumulated new DRMs with a mean number (SD) of 1.4 (2.35) new mutations compared to 0.26 (0.98) in 67 children with wild‐type virus ( P = .003). High pretreatment VL and PDR (number of baseline DRMs) predicted viremia ( P = .003; P = .023) as well as acquired drug resistance ( P = .02; P = .04). Conclusion Pretreatment drug resistance to NNRTI/NRTI was common among ART‐naïve Ugandan children and predicted viremia and new resistance mutations after only 24 weeks of efavirenz‐based therapy. PDR may compromise long‐term ART outcomes—especially when access to resistance testing and VL monitoring is poor. The long‐term importance of PDR for non‐NNRTI‐based regimens needs further evaluation.