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Observational Study
. 2020 Dec;109(12):2706-2716.
doi: 10.1111/apa.15320. Epub 2020 May 26.

Pretreatment HIV drug resistance predicts accumulation of new mutations in ART-naïve Ugandan children

Sandra Soeria-Atmadja  1   2 , Pauline Amuge  3 , Sarah Nanzigu  4 , Dickson Bbuye  3 , Johanna Rubin  1 , Jaran Eriksen  5   6 , Adeodata Kekitiinwa  3 , Celestino Obua  7 , Lars L Gustafsson  5 , Lars Navér  1   2
Affiliations
Observational Study

Pretreatment HIV drug resistance predicts accumulation of new mutations in ART-naïve Ugandan children

Sandra Soeria-Atmadja et al. Acta Paediatr. 2020 Dec.

Abstract

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.

Keywords: HIV; Uganda; child; drug resistance; efavirenz; viral.

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References

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