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

Abstract

Background Despite the increased use of combined antiretroviral therapy (cART) to suppress the HIV viral load and increase the CD4 + T-cell counts, there are disparities in response to cART. This study explores population-sensitive, demographic, and clinical factors affecting short-term immunologic reconstitution following initiation of cART in HIV-infected children. Methodology: A retrospective study of children followed in Orotta National Pediatric Referral Hospital from 2005–2020 was conducted. Two separate analyses were performed, and univariate and multivariate logistic regression models were employed to assess the risk factors associated with inadequate IR at 6- and 12-months following 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]. We analyzed 456 and 495 children with complete data at 6 and 12 months of follow-up periods, respectively. 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 NNNRTI (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 Lower baseline absolute CD4 count was independently associated with the IR following treatment with cART. However, Children initiated on EFV and males exhibited higher odds of inadequate IR after 6 and 12 months on cART, respectively. Identifying population-specific risk factors and gender-targeted intervention tools has promising potential to design effective therapeutic strategies that will enhance the reconstitution of CD4 T-cells and have a beneficial impact on sub-Saharan HIV-infected children receiving cART in sub-optimal and resource-constrained settings.