Population-Specific Predictors of Immunologic Reconstitution Following Initiation of Combined Antiretroviral Therapy in Children: A Retrospective Observational Study from a 15-Year Cohort of HIV-Positive Children and Adolescents in Eritrea.

Background: In the landscape of HIV treatment, combined antiretroviral therapy (cART) is a cornerstone in managing viral loads and boosting CD4+ T-cell counts. Nevertheless, disparities in treatment outcomes remain persistent, and a subset of children fail to achieve adequate immunologic reconstitution (IR). This study aims to investigate the demographic and clinical factors associated with inadequate IR in HIV-infected children in Eritrea.

Methodology: A retrospective observational study was conducted on 822 children followed at Orotta National Pediatric Referral Hospital between 2005 and 2020. Two distinct analyses were performed, with univariate and multivariate logistic regression models employed to investigate risk factors contributing to inadequate immunologic reconstitution (IR) at the study endpoints of 6- and 12-months post-cART initiation.

Results: From the initial cohort of 822 patients [53.4% were males, cohort median age at cART initiation was 78 (IQR: 48-101) months and median absolute CD4 count 270 (151-441) cells/µL]. Two separate analyses were conducted on two cohort subsets with complete data, including 456 children at the 6-month mark and 495 children at 12 months of follow-up. Following 6 months on cART, Immunologic reconstitution was achieved in 87.8% (95% CI: 84.3-91.2) and increased to 90.4% (95% CI: 87.3-93.5) after 12 months of treatment. Independent predictors of inadequate IR after 6 months of cART were higher baseline absolute CD4 counts (aOR = 1.003, (95% CI: 1.002-1.005); p-value <0.001) and NNRTI (EFV: aOR = 3.9, (95% CI: 1.3-11.9); p-value = 0.01). Meanwhile, gender (females: aOR = 0.3, (95% CI: 0.1-0.9, p-value = 0.03) and higher baseline absolute CD4 counts (aOR = 1.003, (95% CI: 1.002-1.005); p-value < 0.001) were independent risk factors of inadequate IR after 12 months of treatment.

Conclusion: The study underscores the interplay of baseline CD4 count, gender, and regimen choice in shaping the effectiveness of cART in children. Lower baseline absolute CD4 count was associated with IR after starting cART. Notably, children on EFV had a higher likelihood of inadequate IR after 6 months, and male children were more prone to insufficient IR at 12 months. Targeting these population-specific factors may be pivotal in advancing gender-responsive therapeutic strategies and improving health outcomes for HIV-infected children in sub-optimal clinical settings and resource-constrained environments.