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. 2024 Oct 1;43(10):970-976.
doi: 10.1097/INF.0000000000004482. Epub 2024 Jul 23.

HIV Drug Resistance in Newly Diagnosed Young Children in the Western Cape, South Africa

Kim Anderson  1 , Gert van Zyl  2 , Nei-Yuan Hsiao  3 , Mathilda Claassen  2 , Vanessa Mudaly  4 , Jacqueline Voget  4 , Alexa Heekes  5 , Emma Kalk  1 , Florence Phelanyane  5 , Andrew Boulle  1   5   6 , Gayathri Sridhar  7 , Leigh Ragone  7 , Vani Vannappagari  7 , Mary-Ann Davies  1   5   6
Affiliations

HIV Drug Resistance in Newly Diagnosed Young Children in the Western Cape, South Africa

Kim Anderson et al. Pediatr Infect Dis J. .

Abstract

Background: Pretreatment of HIV drug resistance among children living with HIV (CLHIV) can compromise antiretroviral therapy (ART) effectiveness. Resistance may be transmitted directly from mothers or acquired following exposure to antiretrovirals consumed through breastfeeding or administered as prophylaxis.

Methods: We performed resistance testing in children aged <3 years, newly diagnosed with HIV in Western Cape, South Africa (2021-2022), who either (1) acquired HIV via possible breastfeeding transmission from mothers who received ART (any regimen) during pregnancy/postpartum and/or (2) were exposed to protease inhibitors or integrase strand transfer inhibitors (INSTIs) in utero. Possible breastfeeding transmission was defined as testing HIV-polymerase chain reaction positive at age >28 days, after previously testing negative. We used surveillance drug-resistance mutation lists to define mutations.

Results: We included 135 CLHIV. Most mothers started ART prepregnancy (73%). Overall, 57% (77/135) of children had resistance mutations detected. Nonnucleoside reverse transcriptase inhibitor-associated, nucleoside reverse transcriptase inhibitor-associated, protease inhibitor-associated and INSTI-associated mutations were found in 55% (74/135), 10% (13/135), <1% (1/135) and <1% (1/122) of children tested, respectively. One child with breastfeeding transmission had high-level INSTI resistance detected at HIV diagnosis, aged 18 months (E138K and G118R mutations).

Conclusions: Although not clinically relevant, nonnucleoside reverse transcriptase inhibitor-associated mutations were common. Dolutegravir is currently the preferred first-line treatment for adults and CLHIV age ≥4 weeks, and although very low INSTI resistance levels have been observed in adults, limited data exist on genotyping the integrase region in children. Pretreatment INSTI resistance in children is likely to be unusual, but future surveillance, including longitudinal studies with paired mother-child resistance testing, is needed.

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Conflict of interest statement

K.A., E.K. and M.-A.D. received funding from ViiV Healthcare for this project. The Provincial Health Data Centre was supported by grant U01AI069924 from National Institutes of Health (National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Cancer Institute, National Institute on Drug Abuse and National Institute of Mental Health)—Principal Investigator: M. Egger and M.-A.D. E.K., A.B. and M.-A.D. were supported by grant R01HD080465 from National Institutes of Health (National Institute of Child Health and Human Development). The other authors have no conflicts of interest to disclose.

Figures

Figure 1:
Figure 1:
(A) Proportion of children with between 0 and 5 HIV drug resistance mutations each (n=135 children) and (B) HIV drug class resistance associated with mutations detected in 77 children Abbreviations: NNRTI non-nucleoside reverse transcriptase inhibitor, NRTI nucleoside reverse transcriptase inhibitor, PI protease inhibitor, INSTI integrase strand transfer inhibitor
Figure 2:
Figure 2:
Timeline showing maternal antiretroviral treatment and laboratory results from the year of maternal HIV diagnosis, and timing of pregnancy and child HIV-PCR tests
See this image and copyright information in PMC

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