HIV-exposed Uninfected Children Research Articles

Clinical and immunological outcomes of HIV-exposed uninfected and HIV-unexposed uninfected children in the first 24months of life in Western Kenya.

Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24months of life. Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

Effects of Moderate Acute Malnutrition Treatment and HIV-Exposure on Body Composition among Children Under Five Years in SubSaharan Africa: A systematic review

Background: Malnutrition poses a global threat to Childhood growth and survival. Coupled with HIV exposure and infection, under-nutrition risk is greatly increased. Infection with HIV results in Acquired Immune Deficiency Syndrome which increases the body’s nutrient requirements and may significantly affect the body composition parameters. This study aimed to review data from published articles to identify the changes in body composition among children under five in sub-Saharan Africa as a result of Moderate Acute Malnutrition (MAM) and HIV exposure
 Materials And Methods: We conducted a systematic review of published articles on body composition, moderate acute malnutrition treatment and HIV exposure among children under five years. Data was searched from PubMed, Ovid-MedLine, Google Scholar, Cochrane Central Register of Controlled Trials and EMBASE. The review was done as per Cochrane reviews and Preferred Reporting Items for Systematic Reviews and MetaAnalyses guidelines (PRISMA). The articles were then screened for suitability of inclusion and analysis.
 Results: A total of 1,505 records were identified; 520 articles from PubMed, 535 from Medline and 430 from EMBASE. On the first screening step, 755 duplicate records were removed. Screening the articles by abstract and title led to the elimination of 717 records. Further, 88 records were excluded due to a lack of full-text articles, not related to the topic, no prospective studies and the wrong age group (above five years). We finally ended up with 9 articles that were included for review.
 Conclusions: There is an interrelationship between MAM treatment, HIV Exposure and body composition. Treatment of MAM using standard ready-to-use supplemental foods and locally produced specialized nutritious formulas improves the body composition parameters of children under five years. HIV-exposed infected children exhibit poorer body composition parameters than HIV-exposed uninfected and HIV-unexposed uninfected children.

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.

Cardio-Metabolic Health of Offspring Exposed in Utero to Human Immuno-Deficiency Virus and Anti-Retroviral Treatment: A Systematic Review.

Antiretroviral treatment (ART) use during pregnancy continues to rise as it is known to decrease the likelihood of HIV transmission from mother to child. However, it is still unknown whether foetal exposure to (ART) may affect the foetal environment, predisposing the offspring to cardiometabolic risk. Therefore, the aim of this study was to systematically review the cardio-metabolic effects of in utero exposure to HIV/ART on offspring. We carried out a systematic review and obtained literature from the Google scholar, PubMed, ProQuest, Web of Science, and Scopus databases. Two independent reviewers evaluated the titles, abstracts, and full-length English contents. Data from the eligible studies were included. The search yielded 7596 records. After assessing all of these records, 35 of the full-length articles were included in this systematic review. Several studies showed that low birth weight, small head circumference, and altered mitochondrial content were more common among HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected children (HUU). A few studies demonstrated elevated triglyceride levels, lower levels of insulin, and increased blood pressure, oxidative stress, vascular dysfunction, cardiac damage, and myocardial dysfunction among HEU children compared with HUU children. Most findings showed that there were cardio-metabolic health risk factors among HEU children, indicating that maternal exposure to HIV and ART may negatively affect foetal health, which may lead to cardio-metabolic morbidity later in life.

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.

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.

Comorbidities Associated With Increased Risk of Death among Children Aged 2-59 Months with Severe Pneumonia in Western Kenya

Background: Globally, severe pneumonia remains the leading infectious cause of death in children younger than 5 years. Comorbidities increase the risk of death among children with severe pneumonia across age groups and regions; however, the data is scanty on specific comorbidities. The study, therefore, was aimed at improving an understanding of the risk of death due to different comorbidities among children with severe pneumonia. The findings will not only inform the clinical practices but also improve the interventions.&#x0D; Methodology: We conducted a hospital-based cross-sectional study of 141 children aged 2-59 months in Bondo Sub-County hospital in Western Kenya using inpatient data health records of children admitted to the pediatric ward. Both descriptive and inferential statistics were used to determine the occurrence of comorbidities and the risk of death due to comorbidities.&#x0D; Results: The findings show that 57.5% of the children had at least one type of comorbidity including 36.5% malnutrition, 28.6% HIV exposed uninfected, 25.4% sickle cell disease, 7.9% HIV infected and 1.6% other comorbidities. Our findings showed that a child admitted to the hospital with comorbidities had six times increased risk of death compared to a child with severe pneumonia only [OR 6.06 (1.32-27.78) P = 0.02]. We also observed four times increased risk of death among HIV-exposed uninfected children [OR 3.92 95% CI (1.18- 13.04) P = 0.03] and the risk of death increased six times when children had both HIV-exposed uninfected and malnutrition as comorbidities [OR 6.02 95% CI (1.61-22.58) P = 0.008]&#x0D; Conclusion: High comorbidities among children with severe pneumonia and increased risk of death, in HIV-exposed uninfected and malnourished children. There is a need for improved clinical practice and intervention for severe pneumonia, HIV exposed uninfected children. There should be a review of the immunization schedule for pneumonia among HIV-exposed uninfected children.

Cancer risk among HIV-exposed uninfected children in the United States.

In utero exposure to didanosine was associated with increased risk of brain cancer in a French study. We used United States health department records to assess cancer risk among 13 617 children exposed to HIV in utero , who remained HIV-uninfected after birth (1990-2017). Risk of brain tumors was borderline elevated among these children (standardized incidence ratio 2.2, 95% confidence interval 0.8-4.8, P = 0.12, based on six cases). Risk was not significantly increased for leukemia or other cancers.

Longitudinal comparison of insulin resistance and dyslipidemia in children with and without perinatal HIV infection in South Africa.

HIV infection is associated with insulin resistance and dyslipidaemia driven by HIV-associated immune dysregulation and antiretroviral therapy (ART). Children living with perinatally acquired HIV (CHIV) face many decades of exposure to these factors. We evaluated the longitudinal trajectory of insulin resistance and dyslipidaemia in CHIV and HIV-exposed uninfected children (CHEU), compared with children HIV-unexposed (CHU). Four hundred and eighty-five children (141 CHIV, 169 CHEU, 175 CHU) aged 5-16 years, previously part of CHER and P1060 trials, were followed annually at Tygerberg Children's Hospital, South Africa. The primary outcome was Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes included low-density lipoprotein (LDL) cholesterol, triglyceride-to-HDL ratio, android fat mass and SBP. Outcomes were evaluated using linear mixed effects models, adjusting for potential confounders. CHIV had 73% greater HOMA-IR than CHU in ages 6-8 years (95% CI 15.9-158.2%, P < 0.001), and 24.7% greater HOMA-IR than CHU in ages 9-10 years (0.3-55.1%, P = 0.04). By 10-11 years, the difference was not significant (P = 0.161). Longitudinally, triglyceride-to-HDL was 47.94% (34.50-62.73%, P < 0.001) higher in CHIV vs. CHU; LDL was 0.25 mmol/l (0.10-0.39, P = 0.001) higher in CHIV vs. CHU; android fat mass was 11.57% (-21.11 to -0.87%, P = 0.035) lower in CHIV than CHU. No significant difference in SBP was found. CHEU and CHU had similar outcomes. Early-treated CHIV have elevated insulin resistance, which resolves with time. Triglyceride-to-HDL ratio and LDL cholesterol were elevated into puberty. CHIV should be monitored for insulin resistance, dyslipidaemia and subclinical cardiovascular disease.

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 Real-Life Action toward the End of HIV Pandemic: Surveillance of Mother-to-Child HIV Transmission in a Center from Southeast Romania.

Preventing mother-to-child HIV transmission is a strategy to eliminate new infections to move toward a world free of HIV/AIDS. The aim of this study is to assess the effectiveness of the perinatal infection prevention program in a single center from southeast Romania. Newborns of HIV-positive mothers from 2005 to 2020 were followed-up until the age of two in a retrospective study. The transmission rate from HIV-positive mothers to living children was zero, but neonatal mortality, preterm birth and birth defects were still high. The peculiarity of our study is the high proportion of mothers with a nosocomial pattern of HIV transmission. Intensifying the efforts for accurate implementing the interventions for the prevention of mother-to-child HIV transmission, a long time follow-up for HIV-exposed uninfected children and new research on related HIV pregnancies are necessary to reach the objective of a new generation free of HIV.

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.

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus.

HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection.

Prevalence and Risk Factors for Hepatic Steatosis in Children With Perinatal HIV on Early Antiretroviral Therapy Compared to HIV-Exposed Uninfected and HIV-Unexposed Children.

ObjectivesWe evaluated the prevalence and risk factors for hepatic steatosis in South African children with perinatally acquired HIV (PHIV) who started treatment early and remain on long-term antiretroviral therapy (ART) compared to HIV-uninfected children.DesignA cross-sectional study from April 2019 to October 2021. PHIV, HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled from an ongoing cohort study.MethodsAll children had transient elastography (TE) with controlled attenuation parameter (CAP). Liver enzymes, lipogram, insulin and glucose were sent after an overnight fast. Multivariable linear regression analyses identified predictors of CAP. Hepatic steatosis was defined as CAP>248kPa.Results215 children (111 [52%] male; median age 14.1 years; IQR 12.7–14.9) participated in the study, 110 PHIV, 105 HIV-uninfected (36 HEU, 69 HU). PHIV initiated ART at a median age of 2.7 months (IQR 1.8–8.5). Hepatic steatosis prevalence was 9% in PHIV, 3% in HEU and 1% in HU children (p = 0.08). However, 8% of lean (body mass index z-score ≤ +1) PHIV had hepatic steatosis compared to zero lean HEU or HU children (p = 0.03). In multivariable linear regression analysis of all PHIV, body mass index (BMI) z-score was positively associated with CAP (p = 0.001) while CD4 count (p = 0.02) and duration of suppression of HIV viraemia (p = 0.009) were negatively associated with CAP, adjusting for age, sex and ethnicity.ConclusionsHepatic steatosis prevalence was higher in lean PHIV than lean HIV-uninfected South African children. Longer suppression of HIV viraemia and higher CD4 count were associated with lower CAP and might be protective factors for hepatic steatosis in PHIV children.

Early neurodevelopment of HIV-exposed uninfected children in the era of antiretroviral therapy: a systematic review and meta-analysis

SummaryBackgroundThere are 15·4 million children who are HIV-exposed and uninfected worldwide. Early child development crucially influences later academic and socioeconomic factors. However, the neurodevelopmental outcomes of HIV-exposed uninfected (HEU) children in the era of maternal antiretroviral therapy (ART) remain unclear. We aimed to examine the effects of in-utero exposure to HIV and ART on child neurodevelopment.MethodsFor this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, Africa-Wide Information, PsycInfo, and Global Health databases from inception to May 27, 2020, for studies from the past two decades reporting neurodevelopment of HEU children aged 0–5 years compared with HIV-unexposed (HU) children (aim 1), and effects of different maternal ART regimens on neurodevelopment of HEU children (aim 2). We did narrative syntheses for both aims, and a random-effects meta-analysis of high-quality studies comparing HEU children and HU children, to obtain weighted pooled estimates of effect sizes. This study was registered with PROSPERO, CRD42018075910.FindingsWe screened 35 527 records and included 45 articles from 31 studies. Overall, 12 (57%) of 21 studies comparing HEU children and HU children found worse neurodevelopment in HEU children in at least one domain. Study design and methodological quality were variable, with heterogeneity across populations. Meta-analysis included eight high-quality studies comparing 1856 HEU children with 3067 HU children at ages 12–24 months; among HEU children with available data, 1709 (99%) of 1732 were exposed to ART. HEU children had poorer expressive language (effect size –0·17 [95% CI –0·27 to –0·07], p=0·0013) and gross motor function (–0·13 [–0·20 to –0·07], p<0·0001) than HU children, but similar cognitive development (–0·06 [–0·19 to 0·06], p=0·34), receptive language development (–0·10 [–0·23 to 0·03], p=0·14), and fine motor skills (–0·05 [–0·15 to 0·06], p=0·36). Results suggested little or no evidence of an effect of specific maternal ART regimens on neurodevelopment; study heterogeneity prevented meta-analysis.InterpretationHEU children are at risk of subtle impairments in expressive language and gross motor development by age 2 years. We found no consistent effect of maternal ART regimens analysed, although evidence was scarce. We highlight the need for large high-quality longitudinal studies to assess the neurodevelopmental trajectories of HEU children and to investigate underlying mechanisms to inform intervention strategies.FundingWellcome Trust and Medical Research Council.

Neurodevelopment of HIV-exposed uninfected children compared with HIV-unexposed uninfected children during early childhood.

HIV-exposed uninfected (HEU) children during the preschool and early school ages may be at-risk for neurodevelopmental challenges due to in utero and perinatal exposure to HIV and/or antiretroviral (ARV) medications. HEU children and HIV-unexposed uninfected (HUU) children from the community were recruited and tested at 3 to 4 and 5 to 6 years of age. Demographic information, HIV/ARV exposure and measures of intelligence, visuomotor skills, and adaptive functioning were obtained. Nonparametric tests assessed group differences and multiple regression analyses adjusted for demographic variables. Additional multiple regression analyses were performed within the HEU group to investigate associations between neurodevelopmental measures and variables of HIV/ARV exposure. At 3 to 4 years, 211 HEU children and 31 HUU children were assessed, and 144 HEU children and 58 HUU children were assessed at 5 to 6 years of age. At 3 to 4 years of age, HEU children scored significantly lower on measures of Full-Scale IQ, Performance IQ, visual motor integration, and adaptive functioning. At 5 to 6 years of age, HEU children scored significantly lower on all neurodevelopmental measures. At both ages, children who were female and those with mothers who were employed achieved higher scores on measures intellectual ability and/or adaptive functioning. Within the HEU group, no consistent associations were found between neurodevelopmental measures and HIV/ARV specific variables. HEU children demonstrated significantly lower scores on neurodevelopmental measures than HUU children during early childhood. Gaps in verbal intellectual abilities were identified with age, highlighting the importance of monitoring neurodevelopment in this population over time. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Clinical pneumonia in the hospitalised child in Malawi in the post-pneumococcal conjugate vaccine era: a prospective hospital-based observational study

ObjectiveAssess characteristics of clinical pneumonia after introduction of pneumococcal conjugate vaccine (PCV), by HIV exposure status, in children hospitalised in a governmental hospital in Malawi.Methods and findingsWe evaluated 1139 children...

Supplemental Material for Neurodevelopment of HIV-Exposed Uninfected Children Compared With HIV-Unexposed Uninfected Children During Early Childhood

Supplemental Material for Neurodevelopment of HIV-Exposed Uninfected Children Compared With HIV-Unexposed Uninfected Children During Early Childhood

Growth patterns of uninfected children born to women living with perinatally versus nonperinatally acquired HIV.

The aim of this study was to compare long-term growth between HIV-exposed uninfected children (CHEU) born to women with perinatally acquired HIV (CHEU-PHIV) and CHEU born to women with nonperinatally acquired HIV (CHEU-NPHIV). A longitudinal analysis of anthropometric measurements from a U.S.-based multisite prospective cohort study enrolling CHEU and their mothers since April 2007. CHEU were evaluated for growth annually from birth through age 5 and again at age 7 years. Z-scores were calculated using U.S. growth references for weight (WTZ), height (HTZ), and weight-for-length or BMI-for-age (WLZ/BMIZ). Mid-upper arm circumference (MUACZ) and triceps skinfold thickness (TSFZ) Z-scores were obtained from ages 1 and 2, respectively, through age 7 years. Piecewise mixed-effects models, overall and stratified by race and sex, were fit to assess differential growth patterns across age by maternal PHIV status. One thousand four hundred fifty-four singleton infants (286 CHEU-PHIV and 1168 CHEU-NPHIV) were included. CHEU-PHIV had slower growth rates than CHEU-NPHIV for WTZ and WLZ/BMIZ at earlier ages and continued to have lower mean WTZ [-0.27, 95% confidence interval (95% CI): -0.50, -0.04] and WLZ/BMIZ (-0.39, 95% CI: -0.67, -0.11) through age 7. Among non-Black boys, CHEU-PHIV had slightly lower WTZ and WLZ/BMIZ at birth than CHEU-NPHIV and these growth deficits persisted through age 7 years. Compared with CHEU-NPHIV, CHEU-PHIV had diminished growth in early childhood with differences most pronounced among non-Black male children. Further longitudinal follow-up of CHEU-PHIV into young adulthood is needed to understand whether these early effects of maternal PHIV status on growth persist and have other health consequences.

Higher prevalence of stunting and poor growth outcomes in HIV-exposed uninfected than HIV-unexposed infants in Kenya.

With the growing population of HIV-exposed uninfected (HEU) children globally, it is important to determine population-level growth differences between HEU and HIV-unexposed uninfected (HUU) children. We analyzed data from a population-level survey enrolling mother-infant pairs attending 6-week and 9-month immunizations in 140 clinics across Kenya. Weight-for-age (WAZ), length-for-age (LAZ), head circumference-for-age (HCAZ) z-scores and underweight (WAZ < -2), stunting (LAZ < -2), and microcephaly (HCAZ < -2), were compared between HEU and HUU. Correlates of growth faltering and poor growth were assessed using generalized Poisson and linear regression models. Among 2457 infants, 456 (19%) were HEU. Among mothers living with HIV, 64% received antiretroviral therapy (ART) and 22% were on antiretroviral prophylaxis during pregnancy. At 9 months, 72% of HEU and 98% of HUU were breastfeeding. At 6 weeks, HEU had lower mean WAZ (-0.41 vs. -0.09; P < 0.001) and LAZ (-0.99 vs. -0.31; P = 0.001) than HUU. Stunting was higher in HEU than HUU at 6 weeks (34% vs. 18%, P < 0.001) and 9 months (20% vs. 10%, P < 0.001). In multivariable analyses, HEU had lower mean LAZ at 6 weeks (-0.67, 95% confidence interval [CI]: -1.07, -0.26) and 9 months (-0.57, 95% CI: -0.92, -0.21) and HEU had higher stunting prevalence (week-6 adjusted prevalence ratio [aPR]: 1.88, 95% CI: 1.35, 2.63; month-9 aPR: 2.10, 95% CI: 1.41, 3.13). HEU had lower mean head circumference (-0.49, 95% CI: -0.91, -0.07) and higher prevalence of microcephaly (aPR: 2.21, 95% CI: 1.11, 4.41) at 9 months. Despite high maternal ART coverage, HEU had poorer growth than HUU in this large population-level comparison. Optimizing breastfeeding practices in HEU may be useful to improve growth.