Pretreatment HIV drug resistance predicts accumulation of new mutations in ART-naïve Ugandan children.
- Resource Type
- journal article
- 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
- Source
- Acta Paediatrica. Dec2020, Vol. 109 Issue 12, p2706-2716. 11p.
- Subject
- *ANTI-HIV agents
*DRUG resistance
*NON-nucleoside reverse transcriptase inhibitors
*NUCLEOSIDE reverse transcriptase inhibitors
*IMMUNE reconstitution inflammatory syndrome
*VIRAL load
- Language
- ISSN
- 0803-5253
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. [ABSTRACT FROM AUTHOR]