Mortality, Human Immunodeficiency Virus (HIV) Transmission, and Growth in Children Exposed to HIV in Rural Zimbabwe

Abstract

Background: Clinical outcomes of children who are human immunodeficiency virus (HIV)-exposed in sub-Saharan Africa remain uncertain.

Methods: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial evaluated improved infant and young child feeding (IYCF) and/or improved water, sanitation, and hygiene in 2 rural Zimbabwean districts with 15% antenatal HIV prevalence and > 80% prevention of mother-to-child transmission (PMTCT) coverage. Children born between February 2013 and December 2015 had longitudinal HIV testing and anthropometry. We compared mortality and growth between children who were HIV-exposed and HIV-unexposed through 18 months. Children receiving IYCF were excluded from growth analyses.

Results: Fifty-one of 738 (7%) children who were HIV-exposed and 198 of 3989 (5%) children who were HIV-unexposed (CHU) died (hazard ratio, 1.41 [95% confidence interval {CI}, 1.02-1.93]). Twenty-five (3%) children who were HIV-exposed tested HIV positive, 596 (81%) were HIV-exposed uninfected (CHEU), and 117 (16%) had unknown HIV status by 18 months; overall transmission estimates were 4.3%-7.7%. Mean length-for-age z score at 18 months was 0.38 (95% CI, .24-.51) standard deviations lower among CHEU compared to CHU. Among 367 children exposed to HIV in non-IYCF arms, 147 (40%) were alive, HIV-free, and nonstunted at 18 months, compared to 1169 of 1956 (60%) CHU (absolute difference, 20% [95% CI, 15%-26%]).

Conclusions: In rural Zimbabwe, mortality remains 40% higher among children exposed to HIV, vertical transmission exceeds elimination targets, and half of CHEU are stunted. We propose the composite outcome of "alive, HIV free, and thriving" as the long-term goal of PMTCT programs.

Clinical trials registration: NCT01824940.

Keywords: Africa; HIV transmission; children HIV-exposed but uninfected; growth; mortality.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.

Cumulative hazard curves for mortality through 18 months. Kaplan-Meier curves are shown for children who were human immunodeficiency virus (HIV) exposed and children who were HIV unexposed. Hazard ratios were estimated by Cox regression analysis accounting for within-cluster correlation and adjusted for trial arm. Plot halted at 18 months. Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus; HR, hazard ratio.

Figure 2.

Growth outcomes of children who were human immunodeficiency virus (HIV) exposed but uninfected (CHEU) and children who were HIV unexposed (CHU) through 18 months of age. Length-for-age (A), weight-for-age (B), weight-for-length (E), and head circumference-for-age (F) z score growth trajectories in CHEU and CHU through 18 months. Data points are z score with 95% confidence intervals (CIs). Stunting (C), underweight (D), wasting (G), and microcephaly (H) in CHEU and CHU through 18 months. Data points are point prevalence percentages with 95% CIs. Number of children (CHEU/CHU) at each timepoint for length-for-age z score (A) and stunting (C): 176/1014 at 1 month, 116/1061 at 3 months, 215/1231 at 6 months, 220/1318 at 12 months, and 297/1771 at 18 months; weight-for-age z score (B) and underweight (D): 175/991 at Figure 2. Continued. 1 month, 160/1049 at 3 months, 217/1216 at 6 months, 221/1308 at 12 months, and 297/1765 at 18 months; weight-for-length (E) and wasting (G): 175/984 at 1 month, 159/1044 at 3 months, 215/1212 at 6 months, 220/1304 at 12 months, and 295/1762 at 18 months; head circumference-for-age z score (F) and microcephaly (H): 169/1038 at 3 months, 214/1232 at 6 months, 221/1321 at 12 months, and 296/1757 at 18 months (there was no head circumference measurement at 1 month of age). Stunting: length-for-age z score < −2; underweight: weight-for-age z score < −2; wasting: weight-for-length z score < −2; microcephaly: head circumference-for-age z score < −2. Only children in non–infant and young child feeding trial arms were included. *P < .05, **P < .01, ***P < .001. Full details including CIs appear in Supplementary Table 5.

Figure 3.

Proportion of children who were alive, human immunodeficiency virus (HIV) free, and nonstunted at 18 months. Only children in non–infant and young child feeding trial arms were included. HIV exposed, n = 371; HIV unexposed, n = 1956. Among 1956 children who were HIV unexposed, 21 children were born to mothers who tested HIV negative in pregnancy but HIV positive at 18 months postpartum, meaning they became HIV exposed during breastfeeding; of these, 5 of 1956 (0.26%) were HIV positive at 18 months and 1 of 1956 (0.05%) was HIV unknown. Among the 1927 HIV-negative mothers of the 1956 children who were HIV unexposed, 266 (14%) did not undergo repeat HIV testing at 18 months; it is therefore possible that additional children in the HIV-unexposed group became postnatally exposed and therefore infected. The HIV incidence among groups tested was 1.2%, and HIV transmission occurred in 21% of children born to postpartum seroconverting mothers. Assuming similar circumstances, approximately 3 of the 266 mothers may have been HIV positive at 18 months, and there would be