HIV-unexposed Uninfected Children Research Articles

Effects of HIV exposure on anemia and vitamin D nutritional status in children aged 6–24 months: a hospital-based cross-sectional study

There is little research on anemia and vitamin D deficiency in HIV-exposed uninfected (HEU) children. This study was aimed to describe and compare the prevalence of anemia and vitamin D inadequacy in HEU children and HIV-unexposed uninfected (HUU) children, and to examine the associations of HIV exposure with anemia and vitamin D inadequacy. This was a hospital-based descriptive cross-sectional study nested within the Prevention of Mother-to-Child Transmission (PMTCT) of HIV program in Hunan Province during July and September 2022. The HEU children aged 6 to 24 months were recruited from the PMTCT outpatient clinics located in five Municipal Maternal and Child Health Care Hospitals. The HUU children were recruited from routine child health examination clinics in the same five Hospitals. Questionnaires about children’s characteristics and maternal gestational conditions were collected from children’s caregivers, and blood samples were collected from all children. Descriptive statistics, Chi-square test, non-parametric rank sum test, and logistic regression were used for analysis. The study population included 336 HEU children and 334 HUU children. The overall prevalence of anemia in the HEU and HUU children was 10.4% and 8.1%, respectively. The median hemoglobin concentrations were 120 (115–126) g/L in the HEU children and 122 (116–129) g/L in the HUU children. Neither prevalence of anemia nor hemoglobin concentration was significantly different between the two groups (P > 0.05). The prevalence of vitamin D inadequacy in the HEU children (19.6% for deficiency and 25.0% for insufficiency) was significantly higher than that of the HUU children (11.4% for deficiency and 16.2% for insufficiency) (P < 0.001). The median 25(OH)D concentration in the HEU children was significantly lower than that of the HUU children (23.80 (13.50–34.08) vs. 32.08 (18.60–39.32) ng/ml) (P < 0.001). HIV exposure in HEU children was significantly associated with an increased risk of vitamin D deficiency (adjusted OR (AOR) 1.72, 95% CI: 1.13–2.61) and vitamin D insufficiency (AOR 1.53, 95% CI: 1.01–2.34), but not with anemia (AOR 0.80, 95% CI: 0.32–2.01). The PMTCT program shall strengthen vitamin D supplementation in HEU children and caregivers shall appropriately extend the outdoor activity time of HEU children to reduce the occurrence of vitamin D inadequacy.

Poorer longitudinal growth among HIV exposed compared to unexposed infants in Kenya.

Most infants born to women living with HIV (WLH) are HIV-exposed but uninfected exposed infants have poorer growth than HIV-unexposed uninfected children. Few large studies have compared children who are exposed (CHEU) and unexposed (CHUU) in the era of dolutegravir (DTG)-based antiretroviral treatment (ART). Longitudinal study of mother-infant CHEU and CHUU pairs in Nairobi and Western Kenya. Mother-infant pairs were enrolled at 6 weeks postpartum with 6-monthly growth assessments. We compared longitudinal growth between CHEU and CHUU infants during the first year and assessed biological and social factors affecting growth (length and weight-for-age z-scores [LAZ, WAZ] and weight for length z-scores [WLZ]) and stunting (LAZ<-2), underweight (WAZ<-2), and wasting (WLZ<-2) from birth to 1 year. Among 2000 infants (1000 CHEU and 1000 CHUU), CHEU infants had significantly lower LAZ at 6 months (-0.165 (95% CI: -0.274, -0.056), p-value = 0.003) and 12 months (-0.195, 95% CI:-0.294, -0.095, p-value = 0.0001; n = 1616). CHEU infants had a higher prevalence of stunting at 6 months compared to CHUU infants (Prevalence Ratio: 1.45, 95% CI: 1.14, 1.85). Among all children, greater maternal BMI, education, and caregiver-perceived social support were positively associated with growth. Higher maternal and infant comorbidities were associated with growth deficits for CHEU infants. Among CHEU, ART timing (before versus during pregnancy) and ART regimen (dolutegravir(DTG)-based, efavirenz-based, and protease inhibitor/other) did not affect growth. Growth deficits among CHEU persist, despite DTG-based ART. Addressing comorbidities, amplifying social support, and education may improve growth outcomes.

Phenotypic characterization of NK cells in 5-year-old children exposed to maternal HIV and antiretroviral therapy in early-life

BackgroundHIV-exposed uninfected (HEU) children are at increased risk of morbidity during the first years of life. Although the immune responses of HEU infants in early-life are relatively well described, studies of natural killer (NK) cells in older HEU children are lacking. NK cell subsets were analysed in HEU children and compared to those in HIV unexposed uninfected (HUU) children aged ~ five years.MethodsMulti-parametric flow cytometry was used to characterize peripheral blood-derived NK cell CD56, CD16, CD57, NKG2A and KIR3DL1/KIR2DL2/L3 expression, including intracellular perforin and granzyme B. NK cell subsets were compared between HEU children exposed to prenatal antiretroviral therapy (ART) from conception [long-term (HEULT)]; those exposed to ART during pregnancy [medium-term (HEUMT)] with continued exposure throughout the breastfeeding period and HUU peers. Furthermore, clinical data of the children, including sick clinic visits and hospitalizations documented in morbidity diaries from birth to 5 years were compared between HEU and HUU groups. Frequencies of CD56bright and CD56dim NK cell were correlated with these clinical parameters.Results139 children were enrolled however, 133 comprising 43 HEULT, 38 HEUMT and 52 HUU were included in the main analyses. Total NK cell, CD56bright nor CD56dim NK cell proportions differed between HEU and HUU children. However, HEULT children had lower frequencies of CD56dim NK cells compared to HEUMT children, (p = 0.002) which maintained significance after controlling for preterm birth, p = 0.012. No differences were observed between HEULT and HUU. The expressions of NKG2A, KIR3DL1/KIR2DL2/L3 and CD57 on CD56bright and CD56dim NK cells were similar between the three groups. Furthermore, the frequencies of granzyme B and perforin double positive NK cells were similar between the HUU with HEULT and HEUMT children. CD56dim NK cell counts had a significant moderate negative correlation with recurrent respiratory infections (rho=-0.38; p = 0.010) in HUU children and negatively correlated with total sick clinic visits in HEUMT (rho=-0.40, p = 0.064).ConclusionThe proportions of total NK cell, CD56bright and CD56dim NK cells, NK cells inhibitory and differentiation surface marker expression and cytolytic granule-positive cells were similar between HEU and HUU children. These data suggest that early-life HIV/ART exposure may not result in major changes in NK cell subsets at 5 years of age.

Impact of HIV exposure without infection on hospital course and mortality among young children in sub-Saharan Africa: a multi-site cohort study

BackgroundAlthough mortality risk associated with HIV is well described, HIV-exposed uninfected (HEU) young children are also at increased risk of hospitalization and death as compared to HIV-unexposed uninfected (HUU) children. The drivers of poor outcomes among HEU children remain unknown, limiting the development of interventions to support this vulnerable population.MethodsWe performed a secondary analysis of data from a large multi-country prospective cohort [Childhood Acute Illness and Nutrition (CHAIN) Network] study. Data from 5 sites in Uganda, Kenya, and Malawi were included. Hospitalized children aged 2–23 months were followed from an index admission for 6 months after discharge to determine acute and long-term outcomes. Using perinatal HIV exposure (HEU and HUU) as the primary exposure and adjusting for child, caregiver, and household characteristics, we compared inpatient and 30-day survival outcomes, nutritional status, hospital length of stay, illness severity, and utilization of inpatient resources.ResultsWe included 1486 children: 217 HEU and 1269 HUU. HEU children had an increased risk of mortality both during hospitalization [adjusted OR 1.96, 95% CI (1.14–3.37)] and in the 30 days following hospital admission [adjusted hazard ratio 2.20, 95% CI (1.10–4.42)]. Wasting and stunting were more frequent in HEU than HUU children, with adjusted OR 1.41, 95% CI (1.03–1.95) and adjusted OR 1.91, 95% CI (1.34–2.70), respectively. HEU children were also more likely to have a prolonged hospital stay compared to HUU children [adjusted OR 1.58, 95% CI (1.08–2.29)], although admission diagnoses, illness severity at admission, and use of inpatient resources (supplemental oxygen, nasogastric tube, and second-line antibiotics) did not differ significantly between groups.ConclusionsHEU children are more likely to die during hospitalization and within 30 days of admission, to be wasted and stunted upon hospital admission, and to require a prolonged hospital stay, as compared to HUU children. Hospitals in settings with a high prevalence of women-living-with-HIV should ensure that maternal HIV status is established among children requiring admission and build capacity to provide additional hospital monitoring and early post-discharge support for HEU children.

Infectivity and Immunogenicity of Live-Attenuated Respiratory Syncytial Virus Vaccines in Human Immunodeficiency Virus-Exposed Uninfected Children.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines. In a pooled analysis of clinical trials of 7 live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed, uninfected (HUU) children. Nasal washes were collected during the first 28 days after vaccination. Serum RSV-neutralizing and anti-RSV F glycoprotein immunoglobulin G (IgG) antibodies were measured prior to and 56 days after vaccination, and before and after the following winter season. Of 156 children, 90 (58%) were HUU and 66 (42%) were HEU. Seventy-six (84%) HUU and 63 (95%) HEU participants were infected with vaccine (shed vaccine virus and/or had a ≥4-fold rise in serum RSV antibodies at 56 days after vaccination). HUU children had higher serum RSV-neutralizing and anti-RSV F IgG titers prior to vaccination. Compared to HEU children, lower percentages of HUU children had ≥4-fold rises in RSV-neutralizing (67% vs 88%) and anti-RSV F IgG (70% vs 89%) titers at 56 days after vaccination. Live-attenuated RSV vaccines are highly immunogenic in HEU children. Given their increased burden of RSV disease and higher early childhood mortality in some settings, HEU children should be prioritized for vaccination against RSV as these vaccines become available.

Single and two-dose typhoid conjugate vaccine safety and immunogenicity in HIV-exposed uninfected and HIV-unexposed uninfected Malawian children

ABSTRACT Vaccine safety and immunogenicity data in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children are important for decision-making in HIV and typhoid co-endemic countries. In an open-label study, we recruited Malawian HEU and HIV unexposed uninfected (HUU) infants aged 9 – 11 months. HEU participants were randomized to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) at 9 months, Vi-TT at 15 months, or Vi-TT at 9 and 15 months. HUU participants received Vi-TT at 9 and 15 months. Safety outcomes included solicited and unsolicited adverse events (AE) and serious AEs (SAEs) within 7 days, 28 days, and 6 months of vaccination, respectively. Serum was collected before and at day 28 after each vaccination to measure anti-Vi IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Cohort 1 (66 participants) enrollment began 02 December 2019, and follow-up was terminated before completion due to the COVID-19 pandemic. Cohort 2 (100 participants) enrollment began 25 March 2020. Solicited AEs were mostly mild, with no significant differences between HEU and HUU participants or one- and two-dose groups. All six SAEs were unrelated to vaccination. Anti-Vi geometric mean titers (GMT) increased significantly from 4.1 to 4.6 ELISA units (EU)/mL at baseline to 2572.0 – 4117.6 EU/mL on day 28 post-vaccination, and similarly between HEU and HUU participants for both one- and two-dose schedules. All participants seroconverted (>4-fold increase in GMT) by the final study visit. Our findings of comparable safety and immunogenicity of Vi-TT in HUU and HEU children support country introductions with single-dose Vi-TT in HIV-endemic countries.

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&#x0D; 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.&#x0D; 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.&#x0D; 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.

Psychiatric disorders in perinatally HIV-exposed, uninfected children: a systematic review

ABSTRACT The population of perinatally HIV-exposed but uninfected (HEU) children is growing rapidly globally. However, perinatal HIV and antiretroviral (ARV) medicine exposure in HIV-uninfected children has raised concerns about HEU children’s mental well-being. The objective of this study was to systematically review the literature on psychiatric disorders in HEU children. The PRISMA guideline was used as a methodical frame of reference. A systematic search was conducted in 5 databases. Data from the included studies were extracted, and the results were summarized qualitatively. The search identified 1,976 articles of which 105 were eligible for full-text analysis. 13 studies met the inclusion criteria. Eight studies compared psychiatric disorder prevalence in perinatally HIV-infected children with HEU children, and only one study found a difference between the two groups. Three studies found that HEU children had a higher prevalence of psychiatric disorders compared with HIV-unexposed, uninfected (HUU) children. These findings indicate that factors such as psychosocial stress, socioeconomic status, and stigma contribute to the increased risk of mental disorders in HEU children. More research is needed comparing HEU children with HUU children adjusting for potential confounders that might partially explain the higher rates seen in the HIV-exposed population. Prospero ID: CRD42020212420.

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria

BackgroundHIV infection and its management confer a substantial health burden to affected individuals and have been associated with increased risk of oral and dental diseases. In this study, we sought to quantify HIV-associated differences in the prevalence and severity of dental caries in the primary and permanent dentition of 4–11-year-old Nigerian Children.MethodsWe used clinical, laboratory, demographic, and behavioral data obtained from an ongoing cohort study of age-matched HIV-infected (HI, n = 181), HIV-exposed-but-uninfected (HEU, n = 177), and HIV-unexposed-and-uninfected (HUU, n = 186) children. Measures of dental caries experience (i.e., prevalence and severity) were based on dmft/DMFT indices recorded by trained and calibrated clinical examiners. Differences in primary and permanent dentition caries experience between HI, HEU, and HUU were estimated using multivariable logistic and negative binomial regression modeling.ResultsHI children had significantly higher caries experience (33%) compared to HEU (15%) and HUU (22%) children. This difference persisted in fully adjusted analyses [odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.0–2.6], was most pronounced in the permanent dentition (OR = 3.4; 95% CI = 1.2–9.5), and mirrored differences in caries severity. While molars were predominantly affected in both primary and permanent dentitions, caries lesion patterns differed between dentitions. Caries severity was significantly associated with hypoplastic primary teeth, gingival inflammation, and lower CD4 counts.ConclusionsWe found that the higher prevalence and severity of dental caries among HI children was driven by increased burden of permanent dentition caries compared to their uninfected counterparts. The dentition-specific associations identified in this study highlight the need to design and implement age-specific caries prevention strategies. These may include intensified oral hygiene regimens aimed at mitigating the cariogenic impact of hyposalivation among HI children. Similarly, the long-lasting impacts of developmental defects of the enamel in the primary and permanent dentitions must not be ignored.

Anthropometry, body composition, early growth and chronic disease risk factors among Zambian adolescents exposed or not to perinatal maternal HIV.

Early life exposures and growth patterns may affect long-term risk of chronic non-communicable diseases (NCD). We followed up in adolescence two Zambian cohorts (n 322) recruited in infancy to investigate how two early exposures - maternal HIV exposure without HIV infection (HEU) and early growth profile - were associated with later anthropometry, body composition, blood lipids, Hb and HbA1c, blood pressure and grip strength. Although in analyses controlled for age and sex, HEU children were thinner, but not shorter, than HIV-unexposed, uninfected (HUU) children, with further control for socio-demographic factors, these differences were not significant. HEU children had higher HDL-cholesterol than HUU children and marginally lower HbA1c but no other biochemical or clinical differences. We identified three early growth profiles - adequate growth, declining and malnourished - which tracked into adolescence when differences in anthropometry and body fat were still seen. In adolescence, the early malnourished group, compared with the adequate group, had lower blood TAG and higher HDL, lower grip strength (difference: -1·87 kg, 95 % CI -3·47, -0·27; P = 0·02) and higher HbA1c (difference: 0·5 %, 95 % CI 0·2, 0·9; P = 0·005). Lower grip strength and higher HbA1c suggest the early malnourished children could be at increased risk of NCD in later life. Including early growth profile in analyses of HIV exposure reduced the associations between HIV and outcomes. The results suggest that perinatal HIV exposure may have no long-term effects unless accompanied by poor early growth. Reducing the risk of young child malnutrition may lessen children's risk of later NCD.

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).

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

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.

Growth deficits in antiretroviral and HIV-exposed uninfected versus unexposed children in Malawi and Uganda persist through 60 months of age.

To compare childhood physical growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) compared with HIV-unexposed uninfected (HUU) children. Longitudinal follow-up of PROMISE trial (NCT01061151) AHEU and age-matched and sex-matched HUU children, enrolled (September 2013 to October 2014) in Malawi and Uganda. We compared WHO population standardized z-scores [height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ), head-circumference-for-age (HCAZ) at 12, 24, 36, 48, and 60 months of age]. We evaluated HUU versus AHEU [in-utero combination antiretroviral treatment (cART) versus Zidovudine (ZDV) alone]; stratified by country, using longitudinal linear and generalized linear mixed models. Of 466 Malawian and 477 Ugandan children, median maternal age at enrollment was 24.5 years (Malawi) and 27.8 years (Uganda); more than 90% were breastfed through 12 months except Uganda AHEU (64.0%). HAZ scores (adjusted for maternal age, breastfed, and socioeconomic status) were lower among AHEU versus HUU children at every time point, significant (P < 0.05) among Ugandan but not Malawian children. Similar patterns were seen for WAZ but not for WHZ or HCAZ scores. High stunting was observed in both countries, significantly higher in Malawi; and higher among AHEU versus HUU children through 48 months of age, significantly (P < 0.05) among Ugandan but not Malawian children. We found no differences in childhood growth trajectories with in-utero exposures to ZDV compared with cART. AHEU versus HUU children had lower median LAZ and WAZ scores persisting through 60 months of age. However, proportions of children with stunting or underweight decreased after 24 months of age.

Comparing growth velocity of HIV exposed and non-exposed infants: An observational study of infants enrolled in a randomized control trial in Zambia.

BackgroundImpaired growth among infants remains one of the leading nutrition problems globally. In this study, we aimed to compare the growth trajectory rate and evaluate growth trajectory characteristics among children, who are HIV exposed uninfected (HEU) and HIV unexposed uninfected (HUU), under two years in Zambia.MethodOur study used data from the ROVAS II study (PACTR201804003096919), an open-label randomized control trial of two verses three doses of live, attenuated, oral RotarixTM administered 6 &10 weeks or at 6 &10 weeks plus an additional dose at 9 months of age, conducted at George clinic in Lusaka, Zambia. Anthropometric measurements (height and weight) were collected on all scheduled and unscheduled visits. We defined linear growth velocity as the rate of change in height and estimated linear growth velocity as the first derivative of the mixed effect model with fractional polynomial transformations and, thereafter, used the second derivative test to determine the peak height and age at peak heigh.ResultsWe included 212 infants in this study with median age 6 (IQR: 6–6) weeks of age. Of these 97 (45.3%) were female, 35 (16.4%) were stunted, and 59 (27.6%) were exposed to HIV at baseline. Growth velocity was consistently below the 3rd percentile of the WHO linear growth standard for HEU and HUU children. The peak height and age at peak height among HEU children were 74.7 cm (95% CI = 73.9–75.5) and 15.5 months (95% CI = 14.7–16.3) respectively and those for HUU were 73 cm (95% CI = 72.1–74.0) and 15.6 months (95% CI = 14.5–16.6) respectively.ConclusionWe found no difference in growth trajectories between infants who are HEU and HUU. However, the data suggests that poor linear growth is universal and profound in this cohort and may have already occurred in utero.

Caregivers' report of HIV-associated oral manifestations among HIV-unexposed, exposed, and infected Kenyan children.

Few oral health studies have been conducted in HIV-exposed uninfected children, who, like their HIV-infected peers, have altered immunity and perinatal drug exposures. To compare caregiver' self-report of oral diseases, hygiene practices and utilization of routine dental care, between HIV-infected (HIV), HIV-exposed uninfected (HEU), and HIV-unexposed uninfected (HUU) children in Kenya. This nested cross-sectional study was conducted at the Kenyatta National Hospital, Nairobi, Kenya. Caregivers of 196 children (104 HIV-infected, 55 HEU, and 37 HUU) participated in this study. Using a validated questionnaire from the WHO and photographs of HIV-related oral lesions, we collected data on oral diseases and oral health practices. Caregivers of HIV-infected children reported at least one oral disease in their children (42%; HEU [27%]; HUU [17%; P=.008]). Oral candidiasis was the most common disease reported (HIV-infected [24%], HEU [5.5%], and HUU [2.8%; P<.05]). Baseline CD4% was associated with oral candidiasis (OR=0.93, 95% CI: 0.88-0.98). Only 16% of children had ever visited a dentist, and most initiated brushing after 3years of age (83%). Nearly all (98%) caregivers desired a follow-up oral examination. HIV infection/exposure and low CD4% were associated with increased odds of oral diseases. Most caregivers desired a follow-up oral examination for their children.