Clinical Report: Drug Resistance to HIV-1 in Pediatric Populations
Overview
This systematic review and meta-analysis of 72 studies including 9,973 children with HIV reveals a high prevalence of pretreatment drug resistance (PDR) at 32.48% and acquired drug resistance (ADR) at 61.43%, predominantly driven by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. Emerging integrase strand transfer inhibitor (INSTI) resistance, though currently low, underscores the need for ongoing surveillance and treatment strategy adjustments.
Background
Mother-to-child transmission of HIV remains a significant challenge despite advances in prevention programs, with vertical transmission risks historically ranging from 15% to 45%. Prevention of mother-to-child transmission (PMTCT) programs have reduced transmission rates substantially, but failures in PMTCT and pediatric treatment limitations contribute to drug resistance in children with HIV (CWHIV). Pediatric populations face unique challenges including limited treatment options, suboptimal adherence, and higher rates of drug resistance compared to adults. The World Health Organization and UNAIDS have set ambitious targets to improve diagnosis, treatment, and viral suppression in children, but drug resistance threatens these goals.
Data Highlights
Parameter
Prevalence (%)
95% Confidence Interval
Pretreatment Drug Resistance (PDR)
32.48
26.08–39.21
PDR in PMTCT failure cases
43.23
32.94–53.82
NNRTI mutations driving PDR
28.38
18.74–39.08
Acquired Drug Resistance (ADR)
61.43
49.82–72.45
NNRTI mutations driving ADR
65.17
53.95–75.63
INSTI-related ADR
5.53
2.49–9.53
Key Findings
Pretreatment drug resistance (PDR) affects nearly one-third of children with HIV, with higher rates (43.23%) among those who failed PMTCT prophylaxis.
Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations are the primary drivers of both PDR and acquired drug resistance (ADR) in pediatric populations.
Acquired drug resistance is highly prevalent at 61.43%, compromising ART efficacy and increasing risks of viral rebound and transmission.
INSTI-related drug resistance remains low but is emerging, highlighting the need for vigilance as integrase inhibitors become more widely used.
Limited pediatric ART options, suboptimal adherence, and programmatic challenges in low- and middle-income countries exacerbate the risk and impact of HIV drug resistance.
Genotypic resistance testing is critical for managing pediatric HIV to optimize treatment and improve long-term outcomes.
Clinical Implications
The high prevalence of NNRTI-associated drug resistance supports phasing out pediatric NNRTI-based regimens for both PMTCT and treatment. Clinicians should prioritize resistance testing and consider integrase inhibitor-based therapies while monitoring for emerging resistance. Strengthening drug resistance surveillance and addressing adherence barriers are essential to improve treatment success and reduce HIV transmission in children.
Conclusion
Pediatric HIV populations face a substantial burden of drug resistance that threatens treatment efficacy and epidemic control. Tailored treatment strategies and enhanced surveillance are imperative to safeguard the health of children living with HIV.
References
Systematic Review and Meta-Analysis, 2024 -- Drug Resistance to HIV-1 in Pediatric Populations
