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- Title
Pretreatment HIV drug resistance predicts accumulation of new mutations in ART-naïve Ugandan children.
- Authors
Soeria‐Atmadja, Sandra; Amuge, Pauline; Nanzigu, Sarah; Bbuye, Dickson; Rubin, Johanna; Eriksen, Jaran; Kekitiinwa, Adeodata; Obua, Celestino; Gustafsson, Lars L.; Navér, Lars; Soeria-Atmadja, Sandra
- Abstract
<bold>Aim: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>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.
- Subjects
UGANDA; ANTI-HIV agents; DRUG resistance; NON-nucleoside reverse transcriptase inhibitors; NUCLEOSIDE reverse transcriptase inhibitors; IMMUNE reconstitution inflammatory syndrome; VIRAL load
- Publication
Acta Paediatrica, 2020, Vol 109, Issue 12, p2706
- ISSN
0803-5253
- Publication type
journal article
- DOI
10.1111/apa.15320