Dataset Information

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.

SUBMITTER: Yeganeh N

PROVIDER: S-EPMC6226320 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Yeganeh Nava N Watts D Heather DH Xu Jiahong J Kerin Tara T Joao Esau C EC Pilotto Jose Henrique JH Theron Gerhard G Gray Glenda G Santos Breno B Fonseca Rosana R Kreitchmann Regis R Pinto Jorge J Mussi-Pinhata Marisa M MM Veloso Valdilea V Camarca Margaret M Mofenson Lynne L Moye Jack J Nielsen-Saines Karin K

The Pediatric infectious disease journal 20181201 12

<h4>Background</h4>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.<h4>Methods</h4>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 antiretro ...[more]

PMID: 29750766

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Project description:IntroductionChildren who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls.Methods and analysisOne hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4-24 weeks and 4-48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention.Ethics and disseminationEthical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications.Trial registration numberClinicalTrials.gov Identifier: NCT05282485. SANCTR ID number: DOH-27-122021-6543.

Project description:ObjectivesHIV-exposed uninfected (HEU) infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU) infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK) cell activity might occur in HEU infants and predispose them to severe infections.DesignCase-control study using cryopreserved peripheral blood mononuclear cells (PBMCs) at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001) and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005). At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001) and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047), but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFN)γ at birth (0.77 vs. 2.64%, p = 0.008) and at 6 months (4.12 vs. 8.39%, p = 0.001), and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008). Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL)-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory cell function may contribute to the increased susceptibility to infection in HEU infants.

Dataset Information

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

Publications

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

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