HIV-exposed Uninfected Infants Research Articles

Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants

While preventing vertical HIV transmission has been very successful, HIV-exposed uninfected infants (iHEU) experience an elevated risk to infections compared to HIV-unexposed and uninfected infants (iHUU). Here we present a longitudinal multimodal analysis of infant immune ontogeny that highlights the impact of HIV/ARV exposure. Using mass cytometry, we show alterations in T cell memory differentiation between iHEU and iHUU being significant from week 15 of life. The altered memory T cell differentiation in iHEU was preceded by lower TCR Vβ clonotypic diversity and linked to TCR clonal depletion within the naïve T cell compartment. Compared to iHUU, iHEU had elevated CD56loCD16loPerforin+CD38+CD45RA+FcεRIγ+ NK cells at 1 month postpartum and whose abundance pre-vaccination were predictive of vaccine-induced pertussis and rotavirus antibody responses post 3 months of life. Collectively, HIV/ARV exposure disrupted the trajectory of innate and adaptive immunity from birth which may underlie relative vulnerability to infections in iHEU.

Impact of Maternal Viral Suppression on Growth Patterns for HIV-Exposed Uninfected Infants in Kenya.

Children born to mothers living with human immunodeficiency virus (HIV) are at risk for poor health outcomes but data characterizing these associations are limited. Our objective was to determine the impact of maternal viral suppression on growth patterns and malnutrition for infants who are HIV-exposed but uninfected (HEU). We conducted a retrospective cohort analysis of clinical data for infants who were HEU and their mothers (September 2015 - March 2019) in Kenya. Infants were stratified based on maternal viral suppression status (≥ or <1000 copies/mL); t-tests were used to compare groups. Growth indicators were evaluated with Chi-square, Fisher's exact, and area under the curve. Moderate-to-severe underweight status, stunting, and wasting were defined by weight-for-age (WFA), height-for-age (HFA), and weight-for-height (WFH), z-scores ≤2, and were used to define malnutrition. Multivariate logistic regression analyses were performed to evaluate potential associations with malnutrition indicators between WFH and HFA. Among 674 infants who were HEU, 48.7% were male and 85.0% had mothers who were virally suppressed. The median age at first and last clinic visits was 1.5 and 16.4 months, respectively. WFA and HFA z-scores over time differed by sex, and WFA and HFA differed based on maternal viral suppression (P < 0.05). Male infants had higher adjusted odds for stunted status, and as children aged, they had slightly increased odds of becoming underweight or stunted. Maternal viral suppression and timing of maternal antiretroviral therapy initiation in relation to the prevention of vertical transmission (PVT) enrollment did not significantly affect malnutrition indicators. Maternal viral suppression status was not associated with increased odds of more severe malnutrition indicators in children who were HEU. However, overall growth patterns over time, measured by z-scores of growth indicators, did differ based on maternal viral suppression status, and to a lesser degree, by gender.

Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants.

Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure to maternal viraemia, immune dysfunction, and co-infections during pregnancy. In a secondary analysis of the SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, and maternal factors shaping immune development in HIV-exposed uninfected infants. Maternal inflammation and cytomegalovirus viraemia were independently associated with infant deaths: mortality doubled for each log10 rise in maternal C-reactive protein (adjusted hazard ratio (aHR) 2.09; 95% CI 1.33-3.27), and increased 1.6-fold for each log10 rise in maternal cytomegalovirus viral load (aHR 1.62; 95% CI 1.11-2.36). In girls, mortality was more strongly associated with maternal C-reactive protein than cytomegalovirus; in boys, mortality was more strongly associated with cytomegalovirus than C-reactive protein. At age one month, HIV-exposed uninfected infants had a distinct immune milieu, characterised by raised soluble CD14 and an altered CD8 + T-cell compartment. Alterations in immunophenotype and systemic inflammation were generally greater in boys than girls. Collectively, these findings show how the pregnancy immune environment in women with HIV underlies mortality and immune development in their offspring in a sex-differentiated manner, and highlights potential new intervention strategies to transform outcomes of HIV-exposed children. ClinicalTrials.gov/NCT01824940.

Distinct alterations in white matter properties and organization related to maternal treatment initiation in neonates exposed to HIV but uninfected

HIV exposed-uninfected (HEU) infants and children are at risk of developmental delays as compared to HIV uninfected unexposed (HUU) populations. The effects of exposure to in utero HIV and ART regimens on the HEU the developing brain are not well understood. In a cohort of 2-week-old newborns, we used diffusion tensor imaging (DTI) tractography and graph theory to examine the influence of HIV and ART exposure in utero on neonate white matter integrity and organisation. The cohort included HEU infants born to mothers who started ART before conception (HEUpre) and after conception (HEUpost), as well as HUU infants from the same community. We investigated HIV exposure and ART duration group differences in DTI metrics (fractional anisotropy (FA) and mean diffusivity (MD)) and graph measures across white matter. We found increased MD in white matter connections involving the thalamus and limbic system in the HEUpre group compared to HUU. We further identified reduced nodal efficiency in the basal ganglia. Within the HEUpost group, we observed reduced FA in cortical-subcortical and cerebellar connections as well as decreased transitivity in the hindbrain area compared to HUU. Overall, our analysis demonstrated distinct alterations in white matter integrity related to the timing of maternal ART initiation that influence regional brain network properties.

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.

Disturbances in the IgG Antibody Profile in HIV-Exposed Uninfected Infants Associated with Maternal Factors.

Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%-42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.

Risk and rates of hospitalisation in young children: A prospective study of a South African birth cohort.

Children in sub-Saharan Africa (SSA) are disproportionately affected by morbidity and mortality. There is also a growing vulnerable population of children who are HIV-exposed uninfected (HEU). Understanding reasons and risk factors for early-life child hospitalisation will help optimise interventions to improve health outcomes. We investigated hospitalisations from birth to two years in a South African birth cohort study. Mother-child pairs in the Drakenstein Child Health Study were followed from birth to two years with active surveillance for hospital admission and investigation of aetiology and outcome. Incidence, duration, cause, and factors associated with child hospitalisation were investigated, and compared between HEU and HIV-unexposed uninfected (HUU) children. Of 1136 children (247 HEU; 889 HUU), 314 (28%) children were hospitalised in 430 episodes despite >98% childhood vaccination coverage. The highest hospitalisation rate was from 0-6 months, decreasing thereafter; 20% (84/430) of hospitalisations occurred in neonates at birth. Amongst hospitalisations subsequent to discharge after birth, 83% (288/346) had an infectious cause; lower respiratory tract infection (LRTI) was the most common cause (49%;169/346) with respiratory syncytial virus (RSV) responsible for 31% of LRTIs; from 0-6 months, RSV-LRTI accounted for 22% (36/164) of all-cause hospitalisations. HIV exposure was associated with increased incidence rates of hospitalisation in infants (IRR 1.63 [95% CI 1.29-2.05]) and longer hospital admission (p = 0.004). Prematurity (HR 2.82 [95% CI 2.28-3.49]), delayed infant vaccinations (HR 1.43 [95% CI 1.12-1.82]), or raised maternal HIV viral load in HEU infants were risk factors for hospitalisation; breastfeeding was protective (HR 0.69 [95% CI 0.53-0.90]). In conclusion, children in SSA experience high rates of hospitalisation in early life. Infectious causes, especially RSV-LRTI, underly most hospital admissions. HEU children are at greater risk of hospitalisation in infancy compared to HUU children. Available strategies such as promoting breastfeeding, timely vaccination, and optimising antenatal maternal HIV care should be strengthened. New interventions to prevent RSV may have additional impact in reducing hospitalisation.

Morbidity and Mortality of HIV-Exposed Uninfected Infants in a Tertiary Referral Facility in Yaoundé, Cameroon.

Following the recorded progress in the prevention of mother-to-child transmission of HIV in Yaoundé, Cameroon, the proportion of HIV-exposed infants who are uninfected (UIH) is increasing. These children are subject to infectious and non-infectious fragility. The purpose of this study was to assess infectious morbidity and mortality rates among UIH in Yaoundé, Cameroon. We conducted a retrospective cohort study. Infants were included in the study and defined as the study subjects if they were between the ages of 24 months or younger, if they were born to HIV-positive mothers, and if they were confirmed to be HIV-negative. The main study outcomes were morbidity rate (defined as infectious, clinical events that required consultation or hospitalization) and death. Data were entered and saved in the Census and Survey Processing System (Cspro) 7.3. Statistical analyses were performed in R Software 3.6.2. The significance level was set at 0.05. In total, 240 subjects were recruited of whom 53.3% were males. Most of the HIV-positive mothers (95.7%) had used combination antiretroviral (ARV) therapy for at least four weeks during pregnancy. Among the subjects, 93.2% received ARV prophylaxis, 68.7% were exclusively breastfed for six months, 94.7% were fully vaccinated, and 60.6% had received cotrimoxazole up to the detection of the non-infection. Overall, the morbidity rate stood at 34.2%. The incidence of morbidity was 3 per 1,000 child months of the follow-up. The main pathologies were acute respiratory infections (60.79%) and malaria (17.65%). Three deaths were recorded, representing an overall mortality rate of 1.25% for an incidence of 1.1 per 1,000 child months of the follow-up (FU). Clinical events were more frequent in mothers diagnosed with HIV during pregnancy under the azidothymidine (AZT) + lamivudine (3TC) + névirapine (NVP) -based protocol (odds ratio of 3.83 [1.09-14.45; p = 0.039]). Morbidity was also higher for the follow-up periods of less than six months. The overall mortality rate among UIH was low. However, the morbidity rate was considerably higher. Emphasis should be focused on in-care retention for up to 24 months for all UIH, which should include monitoring of HIV-infected mothers prior to pregnancy.

Mitochondrial DNA mutations in HIV-exposed uninfected infants following the cessation of triple antiretroviral drugs.

Mitochondrial mutations in HIV-exposed uninfected (HEU) infants after cessation of ART are rarely studied. We analysed a group of HEU newborns born to mothers with late HIV diagnosis who received three doses of ART immediately after birth. We observed mitochondrial DNA (mtDNA) mutations at different times of withdrawal. The study was based on a clinical trial conducted from 2015 to 2020. Newborns of the intervention group who met the criteria for this study received triple antiretroviral drugs, zidovudine + lamivudine + nevirapine, within 2 h after the birth, as post-partum prophylaxis, and at 14 days were switched to zidovudine + lamivudine + lopinavir/ritonavir, which was continued until 6 weeks of age. From August to November 2019, blood samples from HEU infants were also collected after ceasing 12 months of ART, and analysed for mtDNA. Our study found that mtDNA mutations remained prevalent in HEU infants a few years after three ARTs were stopped immediately after birth. Among them, D-loop, ND1 and CYTB are the first three mutated regions during different withdrawal periods. This pattern of mutations is similar to, but not exactly consistent with, HIV-infected children receiving standard ART. Further studies are needed to determine the effects of these mutations on the development of HEU infants and whether stopping ART leads to the restoration of mitochondrial function.

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.

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.

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.

HIV and SARS-CoV-2 infection in postpartum Kenyan women and their infants.

HIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya. We conducted a nested study of 62 HIV-uninfected and 64 healthy women living with HIV, as well as their HIV-exposed uninfected (N = 61) and HIV-unexposed (N = 64) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between May 1, 2020-February 1, 2022 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on available stool samples from seropositive participants. SARS-CoV-2 seropositivity was found in 66% of the 126 mothers and in 44% of the 125 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR] = 0.810, 95% CI: 0.517-1.27) or infant HIV exposure (HR = 1.47, 95% CI: 0.859-2.53). Maternal SARS-CoV-2 was associated with a two-fold increased risk of infant infection (HR = 2.31, 95% CI: 1.08-4.94). Few participants (13% mothers, 33% infants) had symptoms; no participant experienced severe COVID-19 or death. Seroreversion occurred in about half of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants. These data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection and that antibody responses waned over an average of 8-10 months. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.

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...

Increased risk of group B streptococcal sepsis and meningitis in HIV-exposed uninfected infants in a high-income country.

HEU infants presented an increased risk of GBS sepsis and meningitis. One in each 500 HEU infants of our cohort had a central nervous system infection and 1 in each 200, a GBS infection. Although etiological causes are not well understood, this should be taken into account by physicians when attending this population. • HIV-exposed uninfected infants are at higher risk of severe infections. • An increased susceptibility of these infants to group B Streptococcus infections has been described in low- and high-income countries, including a higher risk of meningitis in a South African cohort. •Group B Streptococcal meningitis is more frequent in HIV-exposed uninfected infants also in high-income countries. •Physicians should be aware of this increased risk when attending these infants.

Evolution of the Gut Microbiome in HIV-Exposed Uninfected and Unexposed Infants during the First Year of Life.

ABSTRACTHIV-exposed uninfected infants (HEU) have abnormal immunologic functions and increased infectious morbidity in the first 6 months of life, which gradually decreases thereafter. The mechanisms underlying HEU immune dysfunctions are unknown. We hypothesized that unique characteristics of the HEU gut microbiota associated with maternal HIV status may underlie the HEU immunologic dysfunctions. We characterized the infant gut, maternal gut, and breast milk microbiomes of mother-infant pairs, including 123 with HEU and 117 with HIV-uninfected infants (HUU), from South Africa. Pan-bacterial 16S rRNA gene sequencing was performed on (i) infant stool at 6, 28, and 62 weeks; (ii) maternal stool at delivery and 62 weeks; and (iii) breast milk at 6 weeks. Infant gut alpha and beta diversities were similar between groups. Microbial composition significantly differed, including 12 genera, 5 families and 1 phylum at 6 weeks; 12 genera and 2 families at 28 weeks; and 2 genera and 2 families at 62 weeks of life. Maternal gut microbiomes significantly differed in beta diversity and microbial composition, and breast milk microbiomes differed in microbial composition only. Infant gut microbiotas extensively overlapped with maternal gut and minimally with breast milk microbiotas. Nevertheless, exclusively breastfed HEU and HUU had less divergent microbiomes than nonexclusively breastfed infants. Feeding pattern and maternal gut microbiome imprint the HEU gut microbiome. Compared to HUU, the HEU gut microbiome prominently differs in early infancy, including increased abundance of taxa previously observed to be present in excess in adults with HIV. The HEU and HUU gut microbiome compositions converge over time, mirroring the kinetics of HEU infectious morbidity risk.

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.