Global, regional, and national prevalence of HIV-1 drug resistance in treatment-naive and treatment-experienced children and adolescents: a systematic review and meta-analysis.

Background: Despite significant reductions in mother-to-child HIV-1 transmission risks due to the advancements and scale-up of antiretroviral therapy (ART), the global burden of HIV-1 drug resistance (HIVDR) in treatment-naive and treatment-experienced children and adolescents remains poorly understood. In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of HIVDR in these populations globally, regionally, and at the country level. Methods: We systematically searched PubMed, Embase, and Web of Science for studies reporting HIVDR in treatment-naive and treatment-experienced children and adolescents from inception to June 28, 2024. Eligible studies reported at least ten successfully genotyped cases. We excluded studies where drug resistance was not reported separately for children and adults or for treatment-naive and treatment-experienced populations. The methodological quality of eligible studies was assessed, and random-effect models were used for meta-analysis to determine the pooled overall and regimen-specific prevalence of one or more HIVDR mutations in these populations globally, regionally, or at the country level. This study is registered with PROSPERO under the number CRD42023424483. Findings: Of 2282 records identified, 136 studies (28,539 HIV-1-infected children from 52 countries) were included for analysis. The overall prevalence of HIVDR is 26.31% (95% CI, 20.76-32.25) among treatment-naive children and 74.16% (95% CI, 67.74-80.13) among treatment-experienced children (p < 0.0001). HIVDR varied widely across subregion with the highest prevalence in Southern Africa (37.80% [95% CI, 26.24-50.08]) and lowest in South America (11.79% [95% CI, 4.91-20.84]) for treatment-naive children while highest in Asia (80.85% [95% CI, 63.76-93.55]) and lowest in Europe (54.39% [95% CI, 28.61-79.03]) for treatment-experienced children. The proportion of viral failure (VF) presented positive correlation with DR prevalence for treatment-experienced children, which increased from 61.23% (95% CI, 47.98-73.72) in proportion of VF <50%-81.17% (95% CI, 71.57-89.28) in proportion of 100%. Meta-regression analysis for both groups showed that only age (naive: p = 0.0005; treated: p < 0.0001) was the sources of heterogeneity. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistances were the most seen mutations among the treatment-naive group, with the HIVDR prevalence more than 10% in Southern Africa, Western and Central Africa, Eastern Africa, Asia, and North America. Both nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI resistances were commonly seen among the treatment-experienced group, varying from 36.33% (95% CI, 11.96-64.93) in North America to 77.54% (95% CI, 62.70-89.58) in South America for NRTI and from 39.98% (95% CI, 13.47-69.97) in Europe to 68.86 (95% CI, 43.91-89.17) in Asia for NNRTI, respectively. Interpretation: This study underscores the significant burden of HIVDR among children and adolescents worldwide, particularly pronounced in sub-Saharan Africa and low-income countries. It emphasizes the critical importance of surveillance in all HIV-1-infected children and advocates for the adoption of dolutegravir (DTG) or other optimal formulations as first-line ART in settings where NNRTI resistance exceeds the WHO's 10% threshold. DTG's high resistance barrier, potent antiviral efficacy, and favorable safety profile makes it a superior choice for managing drug-resistant HIV-1, surpassing traditional antiretroviral therapies. Funding: This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality (No. JCYJ20220531102202005) and the Natural Science Foundation of Guangdong Province (No. 2024A1515012118).