HIV-unexposed Uninfected Infants Research Articles

Metabolic Alterations in Mothers Living with HIV and Their HIV-Exposed, Uninfected Infants.

HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between pregnant women living with HIV (PWLWH) and their HEU infants compared to the uninfected and unexposed controls. Untargeted metabolomic profiling was performed using 1H-NMR spectroscopy on maternal plasma at 28 weeks' gestation and infant plasma at birth, 6/10 weeks, and 6 months. PWLWH were older but, apart from a larger 28 week mid-upper-arm circumference, anthropometrically similar to the controls. At all the time points, HEU infants had a significantly reduced growth compared to HUU infants. PWLWH had lower plasma 3-hydroxybutyric acid, acetoacetic acid, and acetic acid levels. In infants at birth, threonine and myo-inositol levels were lower in the HEU group while formic acid levels were higher. At 6/10 weeks, betaine and tyrosine levels were lower in the HEU group. Finally, at six months, 3-hydroxyisobutyric acid levels were lower while glycine levels were higher in the HEU infants. The NMR analysis has provided preliminary information indicating differences between HEU and HUU infants' plasma metabolites involved in energy utilization, growth, and protection from infection.

Comparison of Feeding Practices and Growth of Urbanized African Infants Aged 6–12 Months Old by Maternal HIV Status in Gauteng Province, South Africa

Appropriate feeding practices are protective against malnutrition and poor growth. We compared feeding practices and growth in HIV-exposed-uninfected (HEU) and HIV-unexposed-uninfected (HUU) between 6-12 months of age in urbanized African infants in South Africa. A repeated cross-sectional analysis was used to determine differences in infant feeding practices and anthropometric measures by HIV exposure status at 6, 9, and 12 months in the Siyakhula study. The study included 181 infants (86 HEU; 95 HUU). Breastfeeding rates were lower in HEU vs. HUU infants at 9 (35.6% vs. 57.3%; p = 0.013) and 12 months (24.7% vs. 48.0%; p = 0.005). Introduction to early complementary foods was common (HEU = 16.2 ± 11.0 vs. HUU = 12.8 ± 9.3 weeks; p = 0.118). Lower weight-for-age Z-scores (WAZ) and head circumference-for-age Z-scores (HCZ) were found in HEU infants at birth. At 6 months, WAZ, length-for-age Z-scores (LAZ), HCZ, and mid-upper-arm circumference-for-age Z-scores (MUACAZ) were lower in HEU vs. HUU infants. At 9 months, lower WAZ, LAZ, and MUACAZ were found in HEU vs. HUU infants. At 12 months, lower WAZ, MUACAZ, and weight-for-length Z-scores (-0.2 ± 1.2 vs. 0.2 ± 1.2; p = 0.020) were observed. HEU infants had lower rates of breastfeeding and poorer growth compared to HUU infants. Maternal HIV exposure affects the feeding practices and growth of infants.

1344. Infectious Morbidity and Mortality of HIV-Exposed, Uninfected Infants Compared with HIV-Unexposed Uninfected Infants in Botswana

Abstract Background Studies have shown increased risk for infection-related hospitalizations among infants HIV-exposed-uninfected (HEU) compared to infants HIV-unexposed-uninfected (HUU). However, limited data exist during an era of expanded antiretroviral therapy (ART) and improved healthcare access in pregnancy. Methods The Tshilo Dikotla study prospectively enrolled pregnant women ≥ 18 years old, both living with HIV (WLHIV) and HIV-seronegative, in Botswana, following mother-infant pairs through 3 years postpartum. Pregnant WLHIV received tenofovir/lamivudine or emtricitabine plus efavirenz or dolutegravir. For this analysis, the primary outcome, infectious morbidity, was hospitalization or death due to an infectious cause for infants in the first 12 months of life. Log-binomial models were fit to assess the association between in utero HIV exposure status and infectious morbidity. Subgroup analysis among infants HEU was performed to assess associations between timing of maternal ART initiation (pre-conception vs. during pregnancy) and infant infectious morbidity. Results Of 464 infants, 314 (67.7%) were HEU. Maternal age was higher among WLHIV (30.3 vs. 24.6 years; p < 0.01), as was gravidity (3.0 vs.1.0; p < 0.01). The proportion of WLHIV reporting senior secondary or tertiary education was lower (43.3% vs 72.0%; p< 0.01). A total of 35 (7.5%) infants were hospitalized/died due to infectious causes [26 (8.3%) HEU vs. 9 (6.0%) HUU (p=0.38)]. The most frequent infections were pneumonia and diarrhea/gastroenteritis. There was no significant difference in infectious morbidity by infant HIV exposure status [adjusted Odds Ratio (aOR), 1.17; 95% Confidence Interval (CI), 0.49, 2.81] after adjusting for maternal age, gravidity, income, and education. No association was found between timing of maternal ART initiation and infectious morbidity (aOR 0.60; 95% CI, 0.25, 1.40) among infants who were HEU, after additionally adjusting for maternal CD4 count and HIV viral load. Characteristics of infants by in utero HIV exposure status Conclusion In this small sub-Saharan African cohort, no detectable associations were observed by infant HIV exposure status or timing of maternal ART initiation and infant infectious morbidity. Larger studies are needed to confirm these findings. Disclosures All Authors: No reported disclosures.

A comparison of weight gain between HIV exposed uninfected and HIV unexposed uninfected infants who received KMC at Chris Hani Baragwanath Academic Hospital.

IntroductionKangaroo Mother Care (KMC) has been associated with improved growth in low birthweight infants and reduction in hypothermia, hypoglycaemia, apnoeas, sepsis, hospital stay, and mortality. The growth of HIV-infected children is poorer than those who are HIV-uninfected. There is paucity of data on weight gain in the HIV-exposed uninfected (HEU) infants compared to HIV-unexposed uninfected (HUU) infants receiving KMC.AimThis study compared the weight gain of HEU and infants HUU from admission to the KMC ward until 12 months corrected age (CA) follow-up visit.MethodsRetrospective record review of the neonates admitted in KMC at Chris Hani Baragwanath Hospital over a 2-year period (2012–2013). The weight gain was assessed via weight velocity using the formula; weight/kg/day from admission to KMC to discharge, and g/ week at term, 3, 6 and 9- and 12-months (CA). The demographics were collected and analyzed using Statistica.ResultsSeventy-seven (129/166) percent of the mothers were HIV negative. HIV negative mothers were younger (25.9 vs. 31.6 years; p = 0.000) and had fewer pregnancies (p = 0.02). There was no difference between the gestational age (30.3 ± 2.53 vs. 30.8 ± 2.88 weeks; p = 0.35) and birthweight (1,345 g ± 234 vs. 1,314 g ± 209; p = 0.47) between HEU and HUU. There were no differences in the weight gain (23.83 g ± 12.2 vs. 23.22 g ± 15.2; p = 0.83) in KMC. There was no differences in weight gain at the different follow-up time points between the two groups.ConclusionBoth HEU and HUU groups of infants showed reasonable weight gain despite maternal HIV status.

Kinetics of pneumococcal antibodies among HIV-exposed, uninfected infants in Botswana

BackgroundStreptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants. MethodsWe conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes. ResultsAt birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55–93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age. ConclusionsBoth HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.

Defective Monocyte Enzymatic Function and an Inhibitory Immune Phenotype in Human Immunodeficiency Virus-Exposed Uninfected African Infants in the Era of Antiretroviral Therapy.

BackgroundHuman immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect.MethodsThirty-four HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort and observed up to 6 weeks of age; and then a subsequent 43 HIV-infected and 61 HIV-uninfected mother-infant pairs were recruited into a longitudinal infant cohort at either: 5–7 to 14–15; or 14–15 to 18–23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HIV-unexposed uninfected (HU) infants.ResultsWe demonstrate (1) altered monocyte phagosomal function and B-cell subset homeostasis and (2) lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-tetanus toxoid immunoglobulin G titers in HEU compared with HU infants. Human herpes virus infection was similar between HEU and HU infants.ConclusionsIn the era of antiretroviral therapy-mediated viral suppression, HIV exposure may dysregulate monocyte and B-cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

Immunoglobulin G passive transfer from mothers to infants: total IgG, IgG subclasses and specific antipneumococcal IgG in 6-week Malawian infants exposed or unexposed to HIV

BackgroundThe impaired transplacental passage of IgG from mothers living with HIV to their infants could be one of the causes of the high vulnerability to infections of HIV-exposed uninfected (HEU) infants, but controversial results have been obtained in different settings. The aim of this study was to assess in 6-week old HEU and HIV-unexposed, uninfected (HUU) Malawian infants the total IgG levels, the subclasses profile and the concentrations of global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG and IgG2.MethodsDried blood spots were collected from 80 infants (40 HEU, 40 HUU) and antibodies concentrations determined by nephelometric method (total IgG and subclasses), or using ELISA (anti-PCP total IgG and IgG2). Results are expressed as median levels with IQR, while the proportions of each subclass out of the total IgG are used to describe the subclasses profile.ResultsAt 6 weeks HEU infants had higher median levels of total IgG and IgG1 and a significantly lower level of IgG2 [0.376 (0.344–0.523) g/l vs 0.485 (0.374–0.781) g/l, p = 0.037] compared to the HUU counterparts. The IgG subclasses distribution confirmed the underrepresentation of IgG2 (IgG2 represented 5.82% of total IgG in HEU and 8.87% in HUU). The anti-PCP IgG and IgG2 levels were significantly lower in HEU infants [8.9 (5.4–15.1) mg/l vs 16.2 (9.61–25.8) mg/l in HUU, p < 0.001, and 2.69 (1.90–4.29) mg/l vs 4.47 (2.96–5.71) mg/l in HUU, p = 0.001, respectively].ConclusionCompared to HUU infants, HEU infants have IgG abnormalities mainly represented by low IgG2 levels, suggesting that despite maternal antiretroviral therapy, the mechanisms of IgG transplacental passage continue to be impaired in women living with HIV. HEU infants also showed a significantly lower level of specific anti-PCP IgG, possibly favouring a high vulnerability to S. pneumoniae infection at an age when protection is mostly depending on maternal IgG.

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

BackgroundCommencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes.MethodsSix hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis.DiscussionThe University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity.Trial registrationClinicalTrial.gov Identifier: NCT04087239. Registered 12 September 2019.

Developmental status of human immunodeficiency virus-exposed uninfected premature infants compared with premature infants who are human immunodeficiency virus unexposed and uninfected

BackgroundThere is growing concern about the developmental outcome of infants exposed to HIV in utero. HIV-infected women are at greater risk of premature delivery which poses a further developmental risk factor.ObjectivesTo determine whether there is a difference between the development of premature infants born at 28–37 weeks gestational age that are HIV exposed but uninfected (HEU) compared with HIV-unexposed uninfected infants (HUU).MethodA cross-sectional study was conducted in a Johannesburg state hospital. Thirty HEU and 30 HUU infants, aged between 16 days and six months, were assessed using the Bayley Scales of Infant and Toddler Development III.ResultsThe two groups were well matched for gestational age and birth weight; however, more HUU infants presented with neonatal complications. HUU infants had lower developmental scores than HEU infants in the language (p = 0.003) and motor (p = 0.037) subscales. Expressive language was more affected in the HUU infants (p = 0.001), and fine (p = 0.001) and gross motor (p = 0.03) were affected as well. HUU infants with neonatal complications such as meningitis (p = 0.02) and neonatal jaundice (NNJ) (p = 0.01) are more likely to present with language and motor delay.ConclusionMeningitis and NNJ have more impact on infant development than in-utero HIV and ARV exposure.Clinical implicationsIt is important for all premature infants to be screened regularly in order to diagnose developmental delays early so as to ensure early intervention and improved quality of life.

HIV-Exposed, Uninfected Infants in Uganda Experience Poorer Growth and Body Composition Trajectories than HIV-Unexposed Infants

Abstract Objectives To determine if HIV-exposed and -uninfected (HEU) infants whose mothers received Option B + have higher odds of experiencing suboptimal growth trajectories than HIV-unexposed uninfected (HUU) infants. Methods Anthropometric measures were taken on 238 infants (HEU = 86) at 1 week and 1,3,6,9, and 12 months. Latent class growth mixture modeling was used to develop trajectories for length-for-age z-scores, weight-for-length z-scores, MUAC, sum of skinfolds, and arm fat area. Multinomial logistic models were built to predict odds of class membership by HIV and food security status, controlling for socioeconomic factors. Results HEU infants had greater odds of being in the shortest two classes (OR = 4.30, P = 0.01 and OR = 10.70, P &amp;lt; 0.01) and lower odds of being in smallest arm fat area class (OR = 0.26, P = 0.01) relative to HUU infants. Food insecurity was associated with a smaller increase in the odds that HEU infants were in the second shortest class (OR interaction = 0.83, P = 0.03). Only among HEU, food insecurity increased odds of being in the lowest sum of skinfolds class (OR interaction = 3.80, P = 0.01). Conclusions HEU experience suboptimal growth patterns compared to unexposed infants. HEU infants are differentially affected by food insecurity. The mechanisms which drive these differences and successful strategies for counteracting any potential harm need further investigation. Funding Sources CL was supported by the Royster Society of Fellows. Data collection was supported by the Feed the Future Innovation Laboratory for Nutrition, which is funded by the United States Agency for International Development (USAID) and based at Tufts University (USAID OAA-L-10- 00006), and by a seed grant for collaborations between Cornell University– Ithaca and Weill Cornell Medical College faculty. EMW was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99/R00 HD086304), the National Institute of Diabetes and Digestive and Kidney Diseases (T32DK091227 and T32DK007559), and PepsiCo Global R + D (unrestricted grant to support research in maternal and child health). SLY was supported by the National Institute of Mental Health (K01MH098902). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.

A Meta-analysis Assessing Diarrhea and Pneumonia in HIV-Exposed Uninfected Compared With HIV-Unexposed Uninfected Infants and Children: Erratum.

A Meta-analysis Assessing Diarrhea and Pneumonia in HIV-Exposed Uninfected Compared With HIV-Unexposed Uninfected Infants and Children: Erratum.

Impact of HIV status and vaccination schedule on bacterial nasopharyngeal carriage following infant immunisation with the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in South Africa

BackgroundNasopharyngeal carriage (NPC) of Streptococcus pneumoniae is a precondition for pneumococcal disease and a source of transmission. This trial evaluated NPC of S. pneumoniae and other pathogens post-vaccination with the pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) South African children. MethodsIn this phase III, open, single‐centre, controlled study (ClinicalTrials.gov: NCT00829010), 484 children were stratified by HIV status: 83 HIV+, 101 HEU, and 300 HUU. HIV+ and HEU children received a 3 + 1 PHiD-CV vaccination schedule: primary vaccination, age 6/10/14 weeks, and booster dose, age 9–10 months. HUU infants were randomised (1:1:1) to 3-dose priming and booster (HUU/3+1); 3-dose priming without booster (HUU/3+0); or 2-dose priming and booster (HUU/2+1). Bacterial NPC was assessed 8 times up to 24–27 months of age. ResultsOverall pneumococcal carriage rates were similar across 3+1 groups irrespective of HIV status; trends towards higher carriage rates in the HIV+ than HEU and HUU/3+1 groups were observed at 24–27 months of age. In HUU children, carriage of any pneumococcal serotype was similar for the three different dosing schedules at all timepoints; carriage of vaccine-type pneumococci tended to be lower at 16–19 months and 24–27 months of age in children who had received a booster dose (HUU/2+1 and HUU/3+1 groups) than in the HUU/3+0 group. Carriage rates of NTHi, Staphylococcus aureus and Moraxella catarrhalis were comparable between all groups. ConclusionsHIV infection or exposure did not seem to alter the effect of PHiD-CV on pneumococcal NPC in children during their first 2 years of life. NPC prevalence of vaccine-type pneumococci following vaccination series tended to be lower in children who had received a booster dose in comparison to those who had not.

Peripheral blood mononuclear cell transcriptomes reveal an over-representation of down-regulated genes associated with immunity in HIV-exposed uninfected infants

HIV-exposed uninfected (HEU) infants are disproportionately at a higher risk of morbidity and mortality, as compared to HIV-unexposed uninfected (HUU) infants. Here, we used transcriptional profiling of peripheral blood mononuclear cells to determine immunological signatures of in utero HIV exposure. We identified 262 differentially expressed genes (DEGs) in HEU compared to HUU infants. Weighted gene co-expression network analysis (WGCNA) identified six modules that had significant associations with clinical traits. Functional enrichment analysis on both DEGs and the six significantly associated modules revealed an enrichment of G-protein coupled receptors and the immune system, specifically affecting neutrophil function and antibacterial responses. Additionally, malaria pathogenicity genes (thrombospondin 1-(THBS 1), interleukin 6 (IL6), and arginine decarboxylase 2 (ADC2)) were down-regulated. Of interest, the down-regulated immunity genes were positively correlated to the expression of epigenetic factors of the histone family and high-mobility group protein B2 (HMGB2), suggesting their role in the dysregulation of the HEU transcriptional landscape. Overall, we show that genes primarily associated with neutrophil mediated immunity were repressed in the HEU infants. Our results suggest that this could be a contributing factor to the increased susceptibility to bacterial infections associated with higher morbidity and mortality commonly reported in HEU infants.

A Meta-analysis Assessing Diarrhea and Pneumonia in HIV-Exposed Uninfected Compared With HIV-Unexposed Uninfected Infants and Children.

Previous studies have demonstrated that HIV-exposed uninfected (HEU) infants and children experience morbidity and mortality at rates exceeding those of their HIV-unexposed uninfected (HUU) counterparts. We sought to summarize the association between HEU vs. HUU infants and children for the outcomes of diarrhea and pneumonia. Meta-analysis. We reviewed studies comparing infants and children in the 2 groups for these infectious disease outcomes, in any setting, from 1993 to 2018 from 6 databases. We included 12 studies, and 17,955 subjects total [n = 5074 (28.3%) HEU and n = 12,881 (71.7%) HUU]. Random-effects models showed HEU infants and children had a 20% increase in the relative risk of acute diarrhea and a 30% increase in the relative risk of pneumonia when compared with their HUU counterparts. When stratifying by time since birth, we showed that HEU vs. HUU children had a 50% and 70% increased risk of diarrhea and pneumonia, respectively, in the first 6 months of life. We show an increased risk of diarrhea and pneumonia for HEU vs. HUU infants and children. Although we acknowledge, and commend, the immense public health success of prevention of mother-to-child transmission, we now have an enlarging population of children that seem to be vulnerable to not only death, but increased morbidity. We need to turn our attention to understanding the underlying mechanism and designing effective public health solutions. Further longitudinal research is needed to elucidate possible underlying immunological and/or sociological mechanisms that explain these differences in morbidity.

Undernutrition of HEU infants in their first 1000 days of life: A case in the urban-low resource setting of Mukuru Slum, Nairobi, Kenya

BackgroundAccording to the Lancet, the successful chemoprophylaxis and the introduction of lifelong antiretroviral therapy programs to eliminate mother to child transmission of HIV has promoted the rise in number of HIV exposed uninfected (HEU) infants. In resource limited settings, these infants are at an increased risk of undernutrition due to risk factors such as low birth weight, food insecurity, household composition, income and improper feeding patterns. As several other studies have suggested, the risk factors vary from one setting to another. This paper delved into reviewing the predisposing undernutrition factors in relation to HIV exposure among infants within the low resource urban setting of Mukuru Slum, in Nairobi, Kenya. MethodsA retrospective cohort study was performed on 160 mother/guardian-child pairs in Mukuru Slum, Nairobi, Kenya. Growth charts of the HIV exposed uninfected infants were studied against a control group of HIV unexposed uninfected infants (HUU). Interviews to collect information on socio economic status, household composition, HIV exposure, infant feeding practices and food insecurity related challenges were done. Data was analyzed using IBM SPSS version 20 and WHO anthroplus software. Descriptive statistics as well as Chi square, t-tests and multivariate analysis was done. ResultsStunting among the HIV exposed uninfected infants was the most common form of undernutrition. 38.9% of the HEU infants were severely stunted (LFAZ), while 5.6% of them were severely wasted (WFLZ), while 24.4% of them were severely underweight. The mean birth weights of the HEU infants (2.953kg) was lower than the HUU (3.195kg). HIV exposure was associated with lower Weight for Length Z score (WFLZ), Weight for Age Z score (WFAZ), Length for Age Z score (LFAZ), BMI for Age Z score (BAZ) and Middle Upper Arm Circumference Z score (MUACZ) (p<0.001). HEU infants were more likely to live in households with lesser number of adults (p=0.016) and higher number of children (p<0.001) as compared to the HUU. Although exclusive breastfeeding was upheld among all infants, the HEU were more likely to rely on Food by Prescription supplements (p<0.001) to meet their daily energy needs. Households with HEU infants were, however, less likely to receive food (p=0.041). Overall the largest effect sizes on undernutrition of all infants was found to be affected by the age of children (ηp2=0.439; p<0.001), sex (ηp2=0.135; p=0.001), HIV exposure (ηp2=0.351; p<0.001) and food aid (ηp2=0.083; p=0.021). ConclusionThis study concluded that, HIV exposed uninfected infants in Mukuru were faced with a high undernutrition risk that was associated with HIV exposure, household composition, food aid and use of food by prescription supplements. These factors provide an insight when managing undernutrition among such infants in other resource limited settings. This study recommends future operational studies to inform HIV programs on exact ways to eliminate undernutrition among the rising number of HEU infants.

HIV-Exposed Uninfected Infants Have Increased Regulatory T Cells That Correlate With Decreased T Cell Function.

Background: HIV-exposed uninfected infants (HEU) are at higher risk of severe infections, hospitalizations and death compared with HIV-unexposed uninfected infants (HUU), but the immune deficit underlying it is not known. To address this gap, we investigated T cell functionality and its relationship to phenotypic profiles of T cells and antigen presenting cells (APC) in HEU and HUU.Methods: Blood mononuclear cells from 55 HEU and 16 HUU were stimulated with Staphylococcal Enterotoxin B (SEB) or mock for 72 h, and tested by flow cytometry for proliferation and expression of Th1, Th2, and regulatory (Treg) markers. In parallel, cells were phenotypically assessed for differentiation profiles of Treg, conventional T cell (Tconv) and APC in unstimulated cells.Results: HEU had lower CD4+ functional responses to SEB/mock and similar CD8+ responses compared with HUU. In the phenotypic T cell panel, HEU showed higher proportions of CD4+ and CD8+ Treg expressing IL10, FOXP3, and CD25; higher effector Tconv and Treg; and lower naïve and CD4+TGFβ+ Treg compared with HUU. In the phenotypic APC panel, HEU showed higher proportions of CD1c+ cDC2, CD123+ pDC, CD16+ inflammatory monocytes and cDC and higher expression of CD103 on CD1c-CD123-CD16-cDC1 compared with HUU. Regression analyses adjusted for HIV exposure and multiple comparisons showed that higher CD8+IL10+ and CD8+FOXP3+ Treg in unstimulated cells were associated with lower CD8+ T cell functional responses to SEB/mock. Functionality was not affected by Tconv differentiation, but higher APC activation in aggregate was associated with higher CD8+IL10+ Treg responses to SEB.Conclusions: T cell functionality was decreased in HEU compared with HUU. High CD8+ Treg proportions were the most important predictors of decreased T cell functionality in HEU and HUU.

Growth of HIV-Exposed Infants in Southwest China: A Comparative Study.

Objectives. Prevention of mother-to-child HIV transmission has been globally successful leading to a decline in HIV-infected infants. Thus, the number of HIV-exposed, but uninfected, infants is increasing. As growth is an important indicator of child health, this study aimed to evaluate growth parameters of HIV-exposed Chinese infants. Methods. A prospective study was conducted among HIV-exposed (HIV-infected and uninfected) infants born during 2007 to 2015 in Liuzhou, China. Their weight and length were assessed longitudinally from birth to 18 months of age and compared with HIV-unexposed, uninfected (HUU) infants from the same region. Results. There were 467 HIV-exposed infants. Four percent of infants were HIV-infected. The mean weight-for-age (WAZ) and length-for-age (LAZ) z scores of HIV-infected infants were significantly lower than those of HIV-exposed but uninfected (HEU) infants during 9 to 18 months and 12 to 18 months of age, respectively. Additionally, the mean WAZ and LAZ scores of HIV-infected infants were significantly lower than HUU infants during the first 12 months and 18 months of life, respectively. The mean WAZ and LAZ scores of HEU infants were significantly lower than HUU infants during the first 12 months and 6 months of life, respectively. HEU infants also had a lower mean weight-for-length z score than HUU infants during the first 6 months. Conclusion. We demonstrated poor growth among HIV-exposed Chinese infants, including HIV-uninfected, compared with HUU infants. The results emphasize the need for nutritional monitoring and interventions for HIV-exposed infants regardless of HIV infection status. Research is needed on long-term growth trajectories and factors affecting growth of HIV-exposed infants in China.

2571. Higher Rates of Hospitalization and Infection-Related Hospitalization Among HIV-Exposed Uninfected Infants Compared with HIV Unexposed Uninfected Infants in the United States

BackgroundStudies from multiple countries have suggested impaired immunity in perinatally HIV-exposed uninfected (HEU) children, with elevated rates of all-cause hospitalization and infections. We estimated the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU children and compared this with HIV-unexposed uninfected (HUU) children in the US Among HEU children, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of infant hospitalization.MethodsWe evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) Study dynamic cohort of the Pediatric HIV/AIDS Cohort Study (PHACS) network who were born 2006–2017 and followed from birth. Data on HUU children were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU children using Poisson regression. Among HEU children, multivariable Poisson regression models were fit to evaluate associations of maternal HIV factors with risk of hospitalization.ResultsOur analysis included 2,404 HEU and 3,605,864 HUU children. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUU children (figure). There was no significant difference in mortality. Among HEU children, maternal HIV disease factors, including viral load, CD4 count, antiretroviral regimen, and mode of HIV acquisition, were not associated with hospitalization rates.ConclusionCompared with HUU, HEU children in the United States have nearly twice the rate of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.Figure:Rates of Hospitalization and Mortality in First 2 Years of Life (95% CI) among SMARTT HEU versus Medicaid HUU in the United States, 2007–2016Disclosures E. G. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends. R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.

Breastfeeding mitigates the effects of maternal HIV on infant infectious morbidity in the Option B+ era.

The effects of in-utero HIV-exposure on infectious morbidity and mortality in settings with universal maternal treatment and high breastfeeding rates are unclear. Further, the benefits of exclusive feeding options have not been assessed in the Option B+ era. We investigated these in two African settings with high breastfeeding uptake and good HIV treatment infrastructure during the first year of life. Cox regression with time-changing variables in a birth cohort of 749 HIV-exposed uninfected and HIV-unexposed uninfected infants from Cape Town, South Africa and Jos, Nigeria. There was no difference in infectious morbidity incidence between HIV-exposed uninfected and HIV-unexposed uninfected infants (hazard ratio 1.01; 95% CI 0.78-1.32) after adjusting for confounding variables. Formula-fed infants had significantly higher infectious morbidity incidence when compared with exclusively breastfed infants (hazard ratio 1.64; 95% CI 1.03-2.63) and mixed-breastfed infants (hazard ratio 1.42; 95% CI 1.00-2.02) after adjusting for potential confounding variables. There was no significant difference in mortality among HIV-exposed infants and HIV-unexposed infants during the first year of life in this cohort (2.04 versus 0.94%, P = 0.38). Notably, exclusive breastfeeding for only 4 months had protective effects on morbidity up to 1 year. In settings with universal antiretroviral coverage and high breastfeeding rates, breastfeeding mitigates the effects of in-utero HIV exposure among infants during the first year of life. These findings support previous recommendations for exclusive breastfeeding among HIV-infected women and highlight the role that breastfeeding plays on the health of infants in settings where exclusive breastfeeding is not always feasible or where replacement feeding is recommended.

Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon.

Evaluate blood mitochondrial DNA (mtDNA) content in HIV/antiretroviral-exposed uninfected (HEU) vs. HIV-unexposed uninfected (HUU) infants and investigate differences in mitochondrial-related metabolites by exposure group. We enrolled a prospective cohort of HIV-infected and HIV-uninfected pregnant woman/infant pairs in Cameroon. Dried blood spot mtDNA : nuclear DNA ratio was measured by monochrome multiplex quantitative polymerase chain reaction in HEU infants exposed to in-utero antiretrovirals and postnatal zidovudine (HEU-Z) or nevirapine (HEU-N), and in HUU infants at 6 weeks of life. Acylcarnitines and branch-chain amino acids (BCAAs) were measured via tandem mass spectrometry and consolidated into seven uncorrelated components using principal component analysis. Linear regression models were fit to assess the association between in-utero/postnatal HIV/antiretroviral exposure and infant mtDNA, adjusting for confounders and principal component analysis-derived acylcarnitine/BCAA component scores. Of 364 singleton infants, 38 were HEU-Z, 117 HEU-N, and 209 HUU. Mean mtDNA content was lowest in HEU-Z infants (140 vs. 160 in HEU-N vs. 174 in HUU, P = 0.004). After adjusting for confounders, HEU-Z infants remained at increased risk for lower mtDNA content compared with HUU infants (β: -4.46, P = 0.045), whereas HEU-N infants did not, compared with HUU infants (β: -1.68, P = 0.269. Furthermore, long-chain acylcarnitines were associated with lower (β: -2.35, P = 0.002) and short-chain and BCAA-related acylcarnitines were associated with higher (β: 2.96, P = 0.001) mtDNA content. Compared with HUU infants, HEU infants receiving postnatal zidovudine appear to be at increased risk for decreased blood mtDNA content which may be associated with altered mitochondrial fuel utilization in HEU-Z infants.