Infectious Morbidity, Mortality and Nutrition in HIV-exposed, Uninfected, Formula-fed Infants: Results From the HPTN 040/PACTG 1043 Trial

Abstract

Background: HIV-exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial.

Methods: Infectious morbidity, mortality and undernutrition were evaluated within a cohort of 1000 HEU infants enrolled between April 2004 and April 2010 in Brazil (n = 766) and South Africa (n = 234) as part of the NICHD/HPTN 040 trial of 3 different antiretroviral regimens to decrease intrapartum HIV vertical transmission.

Results: Twenty-three percent of infants had at least 1 infectious serious adverse effect. Infants born to mothers with <12 years of education [adjusted odds ratio (AOR), 2.6; 95% confidence interval [CI], 1.2-5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR, 9.9; 95% CI, 1.6-63.1) were more likely to have infectious serious adverse effects. At 6 months, the infant mortality rate per 1000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 month of age with 18% having a weight-for-age Z score ≤-2, and 22% with height for Z score ≤-2. The likelihood of infant mortality was greater among infants born in South Africa compared with Brazil (AOR, 6.2; 95% CI, 2.5-15.8), high maternal viral load (AOR, 1.7; 95% CI, 1.01-2.9) and birth weight-for-age Z score ≤-2 (AOR, 5.2; 95% CI, 1.8-14.8).

Conclusions: There were high rates of undernutrition, stunting and infectious serious adverse effect in this study's formula-fed HEU population. Suppressing maternal HIV viral load during the peripartum period may be a modifiable risk factor to decrease infant mortality.

Trial registration: ClinicalTrials.gov NCT00099359.

Figures

Figure 1

Infectious Serious Adverse Events (ISAEs) among Infants from Brazil and South Africa. Y-axis indicates rates of disease per 100 infant years and X-axis indicates infectious categories evaluated. Overall rates of ISAEs per 100 infant years are in dark gray bars, Brazilian ISAE rates per 100 infant years are in midgray bars and South African ISAE rates per 100 infant years are in light gray bars as shown in legend. Gastrointestinal ISAEs were more common in South Africa whereas congenital ISAEs were more frequently diagnosed in Brazil.

Figure 2

Height for Age Z score (HAZ) and Weight for Age Z scores (WAZ) by Study Visit among 1000 infants from Brazil and South Africa. As seen, undernutrition and stunting peaked at 1 month and undernutrition improved by 6 months in both countries.