HIV infection and the incidence of malaria among HIV-exposed children from Tanzania

Abstract

Objective: To determine whether human immunodeficiency virus (HIV) infection is associated with increased risk of malaria incidence and recurrence in children.

Methods: Newborn infants of HIV-infected mothers were enrolled at 6 weeks and followed for 2 years. HIV status was assessed by enzyme-linked immunosorbant assay and confirmed by HIV DNA polymerase chain reaction. Malaria was defined as (1) physician-diagnosed clinical malaria; (2) probable malaria, in which laboratory testing is requested for parasitemia; and (3) blood smear-confirmed malaria. Cox proportional hazards models estimated hazard ratios (HRs) for development of first and second malaria episodes, and generalized estimating equation models estimated malaria rate differences per 100-child-years in relation to time-updated HIV status.

Results: Child HIV infection was associated with clinical (HR, 1.34; 95% confidence interval [CI], 1.12-1.61), probable (HR, 1.47; 95% CI, 1.19-1.81), and confirmed (HR, 1.67; 95% CI, 1.18-2.36) malaria episodes. Per 100 child-years, HIV-infected children experienced 88 (95% CI, 65-113), 36 (95% CI, 19-53), and 20 (95% CI, 9-31) more episodes of clinical, probable, and confirmed malaria episodes, respectively, than HIV-uninfected children. Among children with ≥1 malaria episodes, those with HIV infection developed second clinical (HR, 1.28; 95% CI, 1.04-1.57), probable (HR, 1.60; 95% CI, 1.26-2.14), and confirmed (HR, 2.27; 95% CI, 1.06-3.89) malaria sooner than HIV-uninfected children.

Conclusions: HIV infection is a risk factor for the development of malaria. Proactive malaria disease prevention and treatment is warranted for all children, particularly those with HIV infection in settings of coendemicity.

Figure 1.

Screening, recruitment, and randomization into parent study, and derivation of analytic sample.

Figure 2.

Clinical malaria rates by strata of child CD4 cell percentage (in %) and maternal CD4 cell count (in cells/μL). Estimates are rate differences derived from a generalized estimation equation models with normal distribution, identity link, and unstructured working covariance. Baseline covariates adjusted for include child sex, supplementation (micronutrient vs placebo), birth weight (<2500 vs ≥2500 g), per-capita household daily food expenditure (≤500 vs >500 Tanzanian shillings), maternal age (<25, 25–29, 30–34 vs ≥35 years), maternal education (<7, 7 vs >7 years), and maternal history of prior early neonatal mortality. The time-varying covariates adjusted for include percentage with cotrimoxazole compliance to date, exclusive breast-feeding status, season of visit, maternal CD4 cell count (<350 vs ≥350 cells/μL), and time-updated child CD4 cell percentage (<25% vs ≥25%).