HIV-exposed Uninfected Research Articles

Case history factors and audiological screening outcomes in HEU and HIV unexposed neonates at a district level hospital in Gauteng, South Africa

While progress has been made in reducing vertical Mother to Child Transmission (MTCT) of HIV, limited research exists on the health needs of HIV-exposed uninfected (HEU) neonates, particularly in the field of audiology. This lack of research and evidence could impact early detection and intervention efforts. This study aimed to establish relationships and compare outcomes between case history factors and audiological screening results in HEU and HIV-unexposed neonates at a district-level hospital in Gauteng, South Africa. A non-experimental quantitative, descriptive, cross-sectional, comparative research design was employed. Data was collected with a sample size of 212 participants (100 HEU, 112 HIV-unexposed neonates) recruited using quota sampling. The hearing screening process involved case history assessment, medical file review, otoscopy, tympanometry testing, Distortion Product Evoked Otoacoustic Emissions (DPOAE), and Automated Auditory Brainstem Response (AABR) measurements. Descriptive and inferential statistics, including measures of central tendency and parametric tests, were used for data analysis. The findings indicated that 43% of HEU neonates exhibited refer findings on DPOAE, and 43% on AABR, compared to 26% and 25% respectively in the HIV-unexposed neonatal group. Therefore, a statistically significant relationship was established when comparing audiological results between the HEU and HIV-unexposed groups. Case history factors such as mode of delivery, birth weight, and Apgar scores were not associated with hearing loss in either group. However, in the HEU group, a higher proportion of participants referred on the overall screening in the maternal Retroviral Disease (RVD) stage IV group, although statistical significance was not established. This study fills an evidence gap regarding HEU neonates and highlights the need to include this vulnerable population in policy and clinical guidelines related to early hearing detection, intervention, and preventive audiology initiatives.

Psychiatric Diagnoses Among HIV-Exposed and HIV-Unexposed Uninfected Children: A Danish Nationwide Cohort Study.

This nationwide registry-based cohort study aimed to compare the risk of psychiatric diagnoses among HIV-exposed uninfected (HEU) children with a matched comparison group of HIV-unexposed uninfected (HUU) children, born in Denmark. We hypothesized that HEU children had an increased risk of psychiatric diagnoses and that this increased risk may differ by sex and age. All HEU children born in Denmark between year 2000 and 2020 were included. Each HEU child was matched by year of birth, maternal age at birth, and maternal immigration status to 10 HUU children. The primary outcome was risk of any psychiatric diagnosis (International Classification of Diseases, 10th Revision F00-F99). Incidence rate ratios (IRRs) were estimated using Poisson regression. Analyses stratifying by sex and age were also conducted. In total, 550 HEU children and 5500 HUU children were included. HEU children had an increased risk of any psychiatric disorder [IRR 1.45; 95% confidence interval (CI): 1.04-2.04] in the unadjusted analysis, but in the adjusted analysis, the risk was only significant for children aged 6-11 years [adjusted incidence rate ratio (aIRR) 1.93; 95% CI: 1.14-3.28]. Stratifying by sex, girls aged 6-11 years had an increased risk of any psychiatric disorder (aIRR 3.04; 95% CI: 1.27-7.28), while boys had an increased risk at age 12-20 years (aIRR 2.47; 95% CI: 1.18-5.17). In conclusion, HEU girls aged 6-11 years and HEU boys aged 12-20 years had an increased risk of any psychiatric disorder compared with HUU girls and boys, respectively. These findings highlight the importance of addressing the mental health needs of HEU children/adolescents.

Lower academic performance among children with perinatal HIV exposure in Botswana.

Studies have reported a higher risk of suboptimal neurodevelopment among children who are HIV-exposed uninfected (HEU) compared to children HIV-unexposed uninfected (HUU). Actual academic performance among school-aged children by HIV exposure status has not been studied. Academic performance in Mathematics, Science, English, Setswana and overall among children enrolled in the Botswana-based FLOURISH study who were attending public primary school and ranging in age from 7.1 to 14.6 years were compared by HIV exposure status using a Cochran-Mantel-Haenszel test. Lower academic performance was defined as a grade of "C" or lower (≤60%). Unadjusted and adjusted logistic regression models were fit to assess for an association between HIV exposure and lower academic performance. Between April 2021 and December 2022, 398 children attending public primary school enrolled in the FLOURSH study, 307 (77%) were HEU. Median age was 9.4 years (IQR 8.9-10.2). Only 17.9% of children HEU were breastfeed versus 100% of children HUU. Among children HEU, 80.3% had foetal exposure to three-drug antiretroviral treatment, 18.7% to zidovudine only and 1.0% had no antiretroviral exposure. Caregivers of children HEU were older compared to caregivers of children HUU (median 42 vs. 36 years) and more likely to have no or primary education only (15.0% vs. 1.1%). In unadjusted analyses, children HEU were more likely to have lower overall academic performance compared to their children HUU (odds ratio [OR]: 1.96 [95% confidence interval (CI): 1.16, 3.30]), and lower performance in Mathematics, Science and English. The association was attenuated after adjustment for maternal education, caregiver income, breastfeeding, low birth weight and child sex (aOR: 1.86 [95% CI: 0.78, 4.43]). In this Botswana-based cohort, primary school academic performance was lower among children HEU compared to children HUU. Biological and socio-demographic factors, including child sex, appear to contribute to this difference. Further research is needed to identify modifiable contributors, develop screening tools to identify the risk of poor academic performance and design interventions to mitigate risk.

Effects of Maternal HIV Infection on Early Kaposi Sarcoma-Associated Herpesvirus Seroconversion in a Kenyan Mother-Infant Cohort.

We identified whether maternal human immunodeficiency virus (HIV) infection during pregnancy affects transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV)-specific antibodies and subsequent infant infection. We followed pregnant Kenyan women through delivery and their infants until age 2 years. Children were classified as HIV-exposed uninfected (HEU) or HIV-unexposed uninfected (HUU) based on maternal HIV status. Maternal venous and cord blood at delivery and child venous blood every 6 months were tested for antibodies to 20 KSHV antigens by multiplex bead-based immunoassay. Multiple comparisons were adjusted using false discovery rate (FDR). Maternal HIV infection was significantly associated with decreased transplacental transfer of antibodies against all KSHV antigens and lower cord blood levels for 8 antigens at FDR P < .10. Neither birth to 6-month antibody level changes nor 6-month levels differed in HEU and HUU, except for ORF50. By age 24 months, 74% of children KSHV seroconverted but HEU and HUU did not differ in time to seroconversion nor 2-year seropositivity after adjustment for child malaria infection. Maternal HIV infection reduced a child's initial KSHV antibody levels but did not affect age of infection. Regardless of HIV exposure in utero, KSHV seroconversion in Kenyan children occurred early; associated factors must be identified.

Rates of Seroprotection against Vaccine-Preventable Infectious Diseases in HIV-Exposed and -Unexposed Malawian Infants.

The evaluation of seroprotection rates against vaccine-preventable infectious diseases allows for the identification of risk populations. HIV-exposed infants, even if not infected with HIV, have higher morbidity and mortality in comparison to unexposed counterparts. The aim of this study was to compare the specific IgG levels against Haemophilus influenzae type-B (HiB), Hepatitis-B (HBV), and Streptococcus pneumoniae (Spn) in two groups of infants (HIV-exposed and HIV-unexposed) living in Malawi. Blood samples from 62 infants, 49 HIV-exposed, uninfected (HEU), and born to women living with HIV and 13 HIV-unexposed and uninfected (HUU), were collected at 6 months, and specific IgG levels were determined using ELISA tests. The antibody levels against HiB, HBV, and Spn were similar in the two groups. At six months, all HUU infants and 81.6% of HEU infants showed seroprotective levels against HiB, while a percentage of protection varying from 80.6 to 84.6% was observed for HBV and Spn regardless of HIV exposure. Only 59.2% of HEU and 69.2% of HUU infants showed antibody protection against all three pathogens. These results indicate similar rates of seroprotection among HEU and HUU infants but also suggest that a consistent fraction of infants received incomplete vaccinations. Strategies to enforce participation in immunization programs in Malawi should be a health priority.

Identifying HIV-exposed uninfected children and adolescents in resource-limited settings: the HOPE study experience

HIV-exposed uninfected (HEU) children and adolescents are at higher risk of poor outcomes compared to HIV-unexposed children (HUU). In program settings, it is critical to understand how to identify HEU for screening services. We describe our experience identifying HEU for a neurodevelopment and mental health screening study. We recruited mothers living with HIV (MLHIV) and mothers not living with HIV (MNHIV) and enrolled their HEU or HUU children. We summarise the reasons for ineligibility and recruitment challenges. Among MLHIV, their child’s ineligibility increased with age: 12%, 27%, 50% and 80% in age groups 3–6, 7–10, 11–14, and 15–18, respectively (p < 0.001). Reasons for ineligibility were unknown maternal HIV status during pregnancy or breastfeeding (30%), and maternal disinterest due to fear of inadvertent disclosure of their HIV status to older youth. Recruiting older HEU youth is challenging. Maternal concerns of self-disclosing their HIV status impedes identification of older HEU.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

Inflammatory and Immunologic Biomarkers Associated with Cognitive Impairment in Pediatric and Adolescent Patients with HIV in Lusaka, Zambia: A Sub-Study of the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) (P4-8.005)

<h3>Objective:</h3> Examine differences in monocyte populations and activated platelet-monocyte complexes between HIV-infected and HIV-exposed uninfected (HEU) populations Determine whether soluble biomarkers (including IL-6, sCD163, sCD14, CRP, TNFα, TNFR1, and TNFR2) are associated with cognitive function at baseline Determine whether soluble biomarkers are associated with neurocognitive changes over time <h3>Background:</h3> In 2018, 66,000 children in Zambia under 15 were HIV-positive. HIV is associated with neurocognitive impairment, and current antiretroviral therapy is not protective against some neurological impacts of chronic HIV infection, likely due to CNS inflammation. Though biomarkers conferring risk for neurocognitive impairment are unknown, biomarkers that have implications in monocyte activation and inflammatory response are strong candidates for investigation. Non-classical monocytes and activated platelet-monocyte complexes also play a role in chronic inflammation in the context of HIV, making them strong investigatory candidates, too. <h3>Design/Methods:</h3> This is a sub-study of the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) longitudinal prospective study, through which blood is collected annually. Soluble biomarker quantities were measured by Ella Multiplex Cytokine Analyzer. Classical, intermediate, and non-classical monocyte populations, and platelet-monocyte complexes were determined with flow cytometry. Cognitive function was assessed via a comprehensive neuropsychological testing battery and represented by NPZ8 scores. <h3>Results:</h3> Biomarkers sCD163, sCD14, CRP, and TNFα were significantly higher in concentration (p &lt; 0.05) in the HIV-infected cohort than in the HEU cohort. In contrast, TNF-R1, TNF-R2, and IL-6 were significantly higher in concentration (p &lt; 0.05) in the HEU cohort. When stratified by cognitive performance within cohorts, sCD163, CRP, TNF-R1, TNF-R2, and IL-6 were all found in significantly greater concentration (p &lt; 0.05) in neurocognitively impaired participants. <h3>Conclusions:</h3> Perinatally-acquired HIV is associated with increased levels of several inflammatory serum biomarkers, and biomarker profile characterized by high levels of inflammation and immune activation is associated with poorer cognitive outcomes in HIV-infected youth. <b>Disclosure:</b> Ms. Shah has nothing to disclose. Miss Kabwe has nothing to disclose. Ms. Molinaro has nothing to disclose. Dr. Metro has nothing to disclose. Esau G. Mbewe has received research support from Research was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number K23NS117310. . Pelekelo Kabundula has nothing to disclose. Milimo Mweemba has nothing to disclose. Sylvia Mwanza-Kabaghe has nothing to disclose. The institution of Heather Adams has received research support from Current: NIH; Past: Abeona; Batten Research Alliance; American University Centers on Disabilities. An immediate family member of Heather Adams has received publishing royalties from a publication relating to health care. Heather Adams has received personal compensation in the range of $500-$4,999 for serving as a Consultant with Critical Path Institute. An immediate family member of Dr. Birbeck has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various. Dr. Birbeck has a non-compensated relationship as a Ambassador for Zambia with RSTMH that is relevant to AAN interests or activities. Dr. Bearden has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bearden has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis. Dr. Bearden has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for law firms.

Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children.

To determine immune-metabolic dysregulation in children born to women living with HIV. Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed. Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length. These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.

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.

Assessing environmental enteric dysfunction via multiplex assay and its relation to growth and development among HIV-exposed uninfected Tanzanian infants.

Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants. We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression. In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores. Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study.

Effect of pregnancy versus postpartum maternal isoniazid preventive therapy on infant growth in HIV-exposed uninfected infants: a post-hoc analysis of the TB APPRISE trial

Isoniazid preventive therapy (IPT) initiation during pregnancy was associated with increased incidence of adverse pregnancy outcomes in the TB APPRISE trial. Effects of in utero IPT exposure on infant growth are unknown. This post-hoc analysis used data from the TB APPRISE trial, a multicentre, double-blind, placebo-controlled trial, which randomised women to 28-week IPT starting in pregnancy (pregnancy-IPT) or postpartum week 12 (postpartum-IPT) in eight countries with high tuberculosis prevalence. Participants were enrolled between August 2014 and April 2016. Based on modified intent-to-treat analyses, we analysed only live-born babies who had at least one follow-up after birth and compared time to infant growth faltering between arms to 12 weeks and 48 weeks postpartum in overall and sex-stratified multivariable Cox proportional hazards regression. Factors adjusted in the final models include sex of infant, mother's baseline BMI, age in years, ART regimen, viral load, CD4 count, education, and household food insecurity. Among 898 HIV-exposed uninfected (HEU) infants, 447 (49.8%) were females. Infants in pregnancy-IPT had a 1.47-fold higher risk of becoming underweight by 12 weeks (aHR 1.47 [95% CI: 1.06, 2.03]) than infants in the postpartum-IPT; increased risk persisted to 48 weeks postpartum (aHR 1.34 [95% CI: 1.01, 1.78]). Maternal IPT timing was not associated with stunting or wasting. In sex-stratified analyses, male infants in the pregnancy-IPT arm experienced an increased risk of low birth weight (LBW) (aRR 2.04 [95% CI: 1.16, 3.68), preterm birth (aRR 1.81 [95% CI: 1.04, 3.21]) and becoming underweight by 12 weeks (aHR 2.02 [95% CI: 1.29, 3.18]) and 48 weeks (aHR 1.82 [95% CI: 1.23, 2.69]). Maternal IPT timing did not influence growth in female infants. Maternal IPT during pregnancy was associated with an increased risk of LBW, preterm birth, and becoming underweight among HEU infants, particularly male infants. These data add to prior TB APPRISE data, suggesting that IPT during pregnancy impacts infant growth, which could inform management, and warrants further examination of mechanisms. The TB APPRISE study Supported by the National Institutes of Health (NIH) (award numbers, UM1AI068632 [IMPAACT LOC], UM1AI068616 [IMPAACT SDMC], and UM1AI106716 [IMPAACT LC]) through the National Institute of Allergy and Infectious Diseases, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number, HHSN275201800001I) and the National Institute of Mental Health.

A 12-month Prospective Study of HIV-infected and HIV-uninfected Women and Their Infants in Malawi: Comparative Analysis of Clinical Events and Infant Growth.

Few studies have compared clinical outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) infants in the current scenario of universal and lifelong maternal antiretroviral therapy (ART). HIV-uninfected and HIV-infected Malawian women receiving ART and their breastfed infants were followed for 12 months postpartum, analyzing the rates of infectious and noninfectious events and assessing infant growth at 6 weeks, 6 months, and 12 months. The cohorts included 227 mothers (70 HIV-negative, 157 HIV-positive) and 235 infants (72 HUU, 163 HEU). No maternal or infant deaths occurred during follow-up. HIV-negative women were less likely to complete follow-up (48.6% versus 91.1%). Mothers with and without HIV had similar rates of both infectious and noninfectious events per person-month. Infants who were HEU, compared with HUU, had higher rates of events of any type, lower respiratory tract infections (LRTI), and noninfectious events. HEU had lower body mass index (BMI) at 6 weeks but did not differ from HUU in all anthropometric measures at 6 and 12 months; in growth between 6 weeks and 12 months; and in occurrence of stunting, underweight, and wasting at 6 weeks, 6 months, and 12 months. During the first year of life, infants who were HEU, compared with HUU, showed a transiently lower BMI and an increased risk of LRTI.

Biomarker Profiles and Immunologic Predictors of Neurodevelopment in Children who are HIV Exposed Uninfected

Background: Children who are HIV-exposed uninfected (HEU) have higher morbidity and mortality rates than their unexposed uninfected counterparts (HU). HEU also exhibit lower neurodevelopmental outcomes. Previous studies show that HIV-induced immune dysregulation can be linked to decreased neurodevelopment in HIV+ children. However, the role of inflammation on neurodevelopment in HEU remains unclear. &#x0D; Methods: This study investigated the plasma levels of 81 biomarkers in 82 Kenyan children between the ages of 18 and 36 months. Neurodevelopment was measured using the Bayley Scales of Infant and Toddler Development, 3rd edition. Bayesian model averaging was used to identify significant biomarkers. &#x0D; Results: HEU showed lower levels of 12 different proinflammatorycytokines/chemokines/growth factors: IL-12, leukemia inhibitory factor (LIF), macrophage migration inhibitory factor (MIF), TNF-related weak inducer of apoptosis (TWEAK), and A proliferation inducing ligand (APRIL); BLC, eoxtaxin-2, I-TAC, monokine induced by gamma interferon (MIG), and MIP-3a; fibroblast growth factor-2 (FGF-2) and granulocyte colony-stimulating factor (G-CSF). HEU showed higher levels of 2 inhibitory soluble immune checkpoints: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and CD40. Bayesian model averaging identified the biomarkers to best predict HEU vs. HU status were IL-12, IL-13, and CD40. In HU children, hepatocyte growth factor (HGF) and IL-5 predicted cognitive scores, BLC and IL-7 predicted motor outcomes, and IL-1a, IL-2R, IL-5, and maternal education predicted language scores. In HEU, FGF-2 predicted language scores, and IL-22 predicted motor development. Statistical analysis identified IL-2R and IL-22 as the strongest predictors of neurodevelopmental outcomes in HU and HEU, respectively.&#x0D; Conclusion/Potential Impact: This study shows that HEU exhibit an immune suppressive biomarker profile, rather than an inflammatory profile as indicated in previous studies. The significant biomarkers we found may be used to determine children at risk of decreased poor neurodevelopmental outcomes, allowing more time for intervention.

Survival and health of children who are HIV-exposed uninfected: study protocol for the CHERISH (Children HIV-Exposed Uninfected - Research to Inform Survival and Health) dynamic, prospective, maternal-child cohort study

IntroductionCHERISH is designed to establish a long-term sustainable system for measurement of in utero and postnatal exposures and outcomes in children who are HIV-exposed uninfected (HEU) and HIV-unexposed to compare...

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 &amp;lt; 0.01), as was gravidity (3.0 vs.1.0; p &amp;lt; 0.01). The proportion of WLHIV reporting senior secondary or tertiary education was lower (43.3% vs 72.0%; p&amp;lt; 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.

Mitigating Infectious morbidity and Growth deficits in HIV-exposed uninfected infanTs with human Milk Oligosaccharide (MIGH-T MO): a randomised trial protocol

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...

HIV exposure and its association with paediatric ICU outcomes in children admitted with severe pneumonia at Chris Hani Baragwanath Academic Hospital, South Africa

Background. Pneumonia is one of the leading causes of under-5 death in South Africa and accounts for a substantial burden of paediatric intensive care unit (PICU) admissions. However, little is known about PICU outcomes in HIV-exposed uninfected (HIV-EU) children with pneumonia, despite the growing size of this vulnerable population.Objectives. To determine whether HIV exposure without infection is an independent risk factor for mortality and morbidity in childrenadmitted to PICU with pneumonia.Methods. This retrospective review included all patients with pneumonia admitted to the PICU at Chris Hani Baragwanath AcademicHospital between 1 January 2013 and 31 December 2014. Patients were classified as HIV-unexposed (HIV-U), HIV-EU and HIV-infected.Medical records were reviewed to determine survival to PICU discharge, duration of PICU admission and duration of mechanicalventilation. Survival analysis was used to determine the association between HIV infection/exposure with mortality, and linear regression was used to examine the association with length of stay and duration of mechanical ventilation. This study included 107 patients: 54 were HIV-U; 28 were HIV-EU; 23 HIV-positive; and 2 had an unknown HIV status.Results. Overall, 84% (n=90) survived to PICU discharge, with no difference in survival based on HIV infection or exposure. Both HIV-EUand HIV-U children had significantly shorter PICU admissions and fewer days of mechanical ventilation compared with HIV-infectedchildren (p=0.011 and p=0.004, respectively).Conclusion. HIV-EU children behaved similarly to HIV-U children in terms of mortality, duration of PICU admission and length ofmechanical ventilation. HIV infection was associated with prolonged length of mechanical ventilation and ICU stay but not increasedmortality

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.

Long-Term Persistence of Mitochondrial DNA Instability in HIV-Exposed Uninfected Children during and after Exposure to Antiretroviral Drugs and HIV.

HIV-exposed uninfected (HEU) children show impaired health outcomes during childhood. A high rate of mitochondrial DNA (mtDNA) instability was reported in the blood of HEU at birth. We aimed to explore the relationship between these health outcomes and mtDNA deletions over time in a case series of 24 HEU children. MtDNA instability was assessed by deep sequencing and analyzed by eKLIPse-v2 algorithm at three time points, namely birth, 1 year, and 6 years of age. Association between mtDNA deletion and health outcomes, including growth, clinical, and neurodevelopmental parameters, were explored using univariate statistical analyses and after stratification with relevant variables. HEU children were selected with an equal male:female ratio. An elevated number of mtDNA deletions and duplications events was observed at 7 days’ post-partum. Median heteroplasmy increased at one year of life and then returned to baseline by six years of age. The mtDNA instability was acquired and was not transmitted by the mother. No risk factors were significantly associated with mtDNA instability. In this small case series, we did not detect any association between any health outcome at 6 years and mtDNA instability measures. A significant effect modification of the association between the duration of maternal prophylaxis and child growth was observed after stratification with heteroplasmy rate. Genomic instability persists over time among HEU children but, despite its extension, stays subclinical at six years.