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Review
. 2025 Jun 26;12(7):ofaf378.
doi: 10.1093/ofid/ofaf378. eCollection 2025 Jul.

HIV-1 Drug Resistance in Children and Implications for Pediatric Treatment Strategies: A Systematic Review and Meta-analysis

Joseph Fokam  1   2   3   4 , Aude Christelle Ka'e  1 , Bouba Yagai  1   5 , Maria Mercedes Santoro  6 , Judith Kose Otieno  7 , Natella Rakhmanina  8   9 , Collins Ambe Chenwi  1   6 , Alex Durand Nka  1 , Ezechiel Ngoufack Jagni Semengue  1 , Davy-Hyacinthe Gouissi  1 , Willy Leroi Pabo Togna  1   4 , Nelly Kamgaing  1 , Tetang Suzie  10 , Desire Takou  1 , Georges Teto  1 , Tatiana Tekoh  1   4 , Jeremiah Efakika Gabisa  1 , Audrey Nayang Mundo  1 , Lum Forgwei  1 , Naomi-Karell Etame  1 , Aurelie Minelle Kengni Ngueko  1   6 , Michel Carlos Tommo Tchouaket  1 , Boris Tchounga  11 , Patrice Tchendjou  11 , Joelle Nounouce Bouba Pamen  12   13 , Rogers Ajeh Awoh  4   14 , Gregory-Edie Halle-Ekane  4 , Giulia Cappelli  1   15   16 , Alexis Ndjolo  1   12 , Francesca Ceccherini-Silberstein  6 , Vittorio Colizzi  1   6 , Jean Kaseya  7 , Nicaise Ndembi  7   17 , Carlo Federico Perno  1   18
Affiliations
Review

HIV-1 Drug Resistance in Children and Implications for Pediatric Treatment Strategies: A Systematic Review and Meta-analysis

Joseph Fokam et al. Open Forum Infect Dis. .

Abstract

Introduction: Failure in the prevention of mother-to-child HIV transmission (PMTCT) and pediatric treatment challenges led to pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in children with HIV (CWHIV).

Method: Interventional and observational data published between 2010 and 2024 on PDR and ADR in CWHIV were included and analyzed by random effects models.

Results: Overall, 72 studies encompassing 9973 children were included. The prevalence (95% CI) of PDR was 32.48% (26.08-39.21), and high among those who failed PMTCT prophylaxis (43.23% [32.94-53.82]) versus those without PMTCT-intervention (P < .01) and driven by nonnucleoside reverse transcriptase inhibitors (NNRTI) mutations (28.38% [18.74-39.08]; P = .013). The prevalence of ADR was 61.43% (49.82-72.45), driven by NNRTI-mutations (65.17% [53.95-75.63]; P < .001). INSTI-ADR was low (5.53% [2.49-9.53]) but emerging.

Conclusion: There are high burdens of PDR and ADR among CWHIV, suggesting the need to phase out pediatric NNRTIs used for either PMTCT or treatment. Emerging INSTI resistance among CWHIV highlights the relevance of drug-resistance surveillance strategies.

Prospero registration no: CRD42023470034.

Keywords: ART; children; systematic review; “acquired drug resistance”; “pretreatment drug resistance”.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts.

Figures

Figure 1.
Figure 1.
Flowchart of the study selection process.
Figure 2.
Figure 2.
Pooled prevalence of pretreatment (A) and acquired drug resistance (B).
Figure 3.
Figure 3.
Geographical distribution of PDR (A) and ADR (B) prevalence between 2010 and early 2024. The cartography was performed considering studies included in the meta-analysis. ADR, acquired drug resistance; PDR, pretreatment drug resistance. Copyrighted: The figure was conceived and adapted by the authors of this review; the base layer of the map was downloaded from http://viewer.nationalmap.gov/viewer/.
Figure 4.
Figure 4.
Trends of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) by median year of sampling. Proportion trend test was used to evaluate the trend of HIVDR (P < .01 for each model). Each circle represents a study, and the diameter of the circle is proportional to the sample size of each study. The line fitted was plotted using regression analysis. (A) PDR and (B) ADR. HIVDR, HIV drug resistance.
See this image and copyright information in PMC

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