HIV-exposed Uninfected Children Research Articles

Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children

IntroductionHIV-exposed uninfected (HEU) infants in tuberculosis (TB) endemic settings are at high risk of Mycobacterium tuberculosis (Mtb) infection and TB disease, even in the absence of known Mtb exposure. Because...

The impact of health programmes to prevent vertical transmission of HIV. Advances, emerging health challenges and research priorities for children exposed to or living with HIV: Perspectives from South Africa.

Over the past three decades, tremendous global progress in preventing and treating paediatric HIV infection has been achieved. This paper highlights the emerging health challenges of HIV-exposed uninfected (HEU) children and the ageing population of children living with HIV (CLHIV), summarises programmatic opportunities for care, and highlights currently conducted research and remaining research priorities in high HIV-prevalence settings such as South Africa. Emerging health challenges amongst HEU children and CLHIV include preterm delivery, suboptimal growth, neurodevelopmental delay, mental health challenges, infectious disease morbidity and mortality, and acute and chronic respiratory illnesses including tuberculosis, pneumonia, bronchiectasis and lymphocytic interstitial pneumonitis. CLHIV and HEU children require three different categories of care: (i) optimal routine child health services applicable to all children; (ii) routine care currently provided to all HEU children and CLHIV, such as HIV testing or viral load monitoring, respectively, and (iii) additional care for CLHIV and HEU children who may have growth, neurodevelopmental, behavioural, cognitive or other deficits such as chronic lung disease, and require varying degrees of specialised care. However, the translation thereof into practice has been hampered by various systemic challenges, including shortages of trained healthcare staff, suboptimal use of the patient-held child's Road to Health book for screening and referral purposes, inadequate numbers and distribution of therapeutic staff, and shortages of assistive/diagnostic devices, where required. Additionally, in low-middle-income high HIV-prevalence settings, there is a lack of evidence-based solutions/models of care to optimise health amongst HEU and CLHIV. Current research priorities include understanding the mechanisms of preterm birth in women living with HIV to optimise preventive interventions; establishing pregnancy pharmacovigilance systems to understand the short-, medium- and long-term impact of in utero ART and HIV exposure; understanding the role of preconception maternal ART on HEU child infectious morbidity and long-term growth and neurodevelopmental trajectories in HEU children and CLHIV, understanding mental health outcomes and support required in HEU children and CLHIV through childhood and adolescence; monitoring HEU child morbidity and mortality compared with HIV-unexposed children; monitoring outcomes of CLHIV who initiated ART very early in life, sometimes with suboptimal ART regimens owing to medication formulation and registration issues; and testing sustainable models of care for HEU children and CLHIV including later reproductive care and support.

Myocardial peak systolic velocity-a tool for cardiac screening of HIV-exposed uninfected children.

HIV-uninfected children exposed prenatally to the virus and to prophylactic antiretroviral therapy are at an uncertain risk of long-term myocardial dysfunction. This study aimed to analyse the structure and function of their ventricles and to identify potential screening tools for this at-risk population. One hundred and fifteen children (77 exposed vs 38 controls) aged between 2.7 and 16.2years were included. An echocardiographic study was performed where both ventricles' dimensions and systolic functions were evaluated. In the left ventricle, parameters related to diastolic function were also analysed. Tissue Doppler values were determined in the basal state and after passive leg raising. Serologic analysis of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) was carried out. The two groups had identical ventricular sizes and left ventricular diastolic functions. However, contractility assessed by myocardial peak systolic velocity was significantly inferior in the exposed group. These systolic echocardiographic differences were present despite similar values of NT-proBNP in both groups.Conclusion: HIV-exposed uninfected children may be vulnerable to ventricular systolic dysfunction at long term. Cardiovascular surveillance and periodic monitoring of biventricular function are therefore recommended. Myocardial peak systolic velocity may be a useful screening tool for this purpose.What is Known:• Previous studies on HIV-exposed uninfected children subjected prenatally to antiretroviral therapy have alerted to potential long-term cardiovascular toxicity effects on the left ventricle.What is New:• The study gives new insights on ventricular function and morphology in HIV-exposed uninfected children.• Myocardial peak systolic velocities are significantly inferior in this paediatric sub-group, therefore long-term cardiac surveillance is recommended.

Impact of HIV and antiretroviral drug exposure on lung growth and function over 2 years in an African Birth Cohort.

To assess the impact of HIV and antiretroviral exposure without infection on lung growth and function over the first 2 years of life. Prospective observational study of an African birth cohort, Drakenstein Child Health Study. Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received antiretroviral therapy (ART) as per local guidelines. The association between HIV and antiretroviral exposure with lung function was assessed using mixed effects modelling. Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume compared with HIV-unexposed infants (1.13 ml, confidence interval: 0.02-2.23, P = 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, confidence interval 0.00-0.34, P = 0.046). First-line ART initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (-2.7 ml, -5.31 to -0.10, P = 0.042), and low maternal CD4 cell counts associated with lower infant tidal over 2 years (-11.1 ml, -18.58-3.58, P = 0.004). HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. These data highlight the importance of ongoing surveillance of respiratory health in HEU children.

Development, Cognition, Adaptive Function and Maladaptive Behavior in HIV-infected and HIV-exposed Uninfected Children Aged 2–9 Years

To compare development/cognition, adaptive function and maladaptive behavior of HIV-infected and HIV-exposed uninfected children between 2 to 9 years with HIV-uninfected controls. This hospital-based cross-sectional study was conducted from November, 2013 to March, 2015. 50 seropositive HIV-infected, 25 HIV-exposed uninfected and 25 HIV-uninfected children between 2 to 9 years were administered Developmental Profile 3, Vineland Adaptive Behavior Scale 2, and Child Behavior Checklist for assessing development, adaptive function and maladaptive behaviour, respectively. Additional data were obtained by history, examination and review of records. Significant developmental/cognitive impairment was observed in 38 (76%), 16 (64%) and 6 (24%) HIV-infected, HIV-exposed uninfected, and HIV-uninfected children, respectively. Significant impairment in adaptive function was found in 12 (24%) and 2 (8%) HIV-infected and HIV-exposed uninfected children, respectively. Maladaptive behavior was not seen in any group. High magnitude of impaired development/cognition and adaptive function in HIV-exposed and HIV-infected children warrants assessment of these domains during follow-up of these children, and incorporation of interventions for these deficits in standard care for this group.

Association between zidovudine-containing antiretroviral therapy exposure in utero and leukocyte telomere length at birth

Zidovudine (ZDV) is a nucleoside reverse transcriptase inhibitor that could cause telomere shortening through inhibition of telomerase. We examined the association between in utero exposure to ZDV and telomere length at birth in HIV-exposed-uninfected (HEU) newborns. We selected 94 ZDV-exposed HEU children and 85 antiretroviral therapy (ART)-unexposed HEU children from the Surveillance Monitoring for ART Toxicities Study and the Women and Infants Transmission Study. We assessed relative telomere length in stored peripheral blood mononuclear cells taken in the first 7 days of life using quantitative polymerase chain reaction. We used linear regression to compare relative telomere length between ZDV-exposed and ART-unexposed children. We additionally evaluated relative telomere length according to maternal and infant characteristics. Relative telomere length was longer in ZDV-exposed children compared with ART-unexposed individuals (adjusted mean ratio difference 0.21, 95% confidence interval 0.15-0.28, P < 0.001). We found an inverse correlation between maternal HIV RNA levels and infant relative telomere length (-0.06 per log10 copies, 95% confidence interval -0.08 to -0.03, P < 0.001). Relative telomere length was not associated with maternal CD4 cell count, maternal age, gestational age, sex, sample storage time, or maternal substance use (P > 0.05). Relative telomere length was longer in ZDV-exposed infants. This difference may reflect beneficial health effects of ART during pregnancy, as we observed an inverse association with maternal HIV RNA levels.

CCR2 Genetic Polymorphism And Its Potential Effect On HIV Acquisition In A Population Of Children Living In The Northern Region Of Cameroon.

Background and objectivesThe association of chemokine receptor-2 (CCR2) polymorphism with HIV transmission or disease progression remains highly controversial. The role of CCR2-64I allele in HIV infection may differ from one population to another because of their genetic background. The objectives of this study were to characterize the CCR2 genetic polymorphism and to determine its potential effect in HIV acquisition in children living in the Northern Region of Cameroon.Materials and methodsA cross-sectional study was carried out in five health facilities in the Northern region of Cameroon. DNA was extracted from the Buffy coat of each participant using the QIAamp®DNA mini kit. The DNA extract was then subjected to polymorphic analyses. CCR2 genotypes were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The Chi-Squared test was used for the assessment of the Hardy-Weinberg equilibrium.ResultsA total of 134 children under 15 years comprised of 38 HIV-exposed infected (28.36%) and 96 HIV-exposed un-infected (71.64%) participants were recruited. Prevalences of 44.78% wild type homozygous, 48.52% heterozygous and 6.7% mutant homozygous alleles were found in the overall population. An allelic frequency of 29.69% for the mutant allele CCR2-64I was found in HIV-exposed un-infected individuals as compared to 34.21% in HIV-infected children (p=0.47).ConclusionThe CCR2-64I allele is relatively common in the Northern Region of Cameroon, with a similar distribution among HIV-exposed un-infected and infected children. As this allele alone does not seem to confer protection against HIV-1 infection, further studies using genotype-combination of CCR2 polymorphism and other single nucleotide polymorphisms would be of great relevance in both HIV prevention and novel therapeutic strategies.

Growth of HIV-uninfected children born to HIV-infected mothers in Guangdong, China: an 18-month longitudinal follow-up study

BackgroundTo evaluate the early growth (weight and length) of HIV-exposed uninfected (HEU) children from the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) program in Guangdong Province, China.MethodsA total of 731 HEU children were longitudinally followed up at 7 time points, with anthropometric measurement conducted of weight and length (supine) in the first 18 months. Z scores were calculated, with and without adjustment for gestational age.ResultsA total of 708 HEU children were included in the final follow-up cohort, and 105 (14.83%) children completed all 7 follow-up visits. The mean of adjusted weight-for-age Z scores in these children was above zero and showed a decreasing trend in 18 months. The mean of adjusted length-for-age Z scores showed a decreasing trend and was above zero in the first 12 months; this declined to under zero at age 18 months. The proportion of underweight was 0.28–2.19% and that of stunting was 0.71–4.63% at each follow-up month-age. Slower growth in HEU children was associated with no sustained food subside after 6 month, mothers’ hemoglobin content less than 100 g/L during pregnancy, preterm birth, and low birth weight (p < 0.05).ConclusionsHEU children could catch up to WHO growth standards in first 18 months in Guangdong; however, growth declined after 12 months, and these children need sustained nutritional support.

364. Association of Maternal ARV Use with Microcephaly in HIV-Exposed Uninfected Children

BackgroundPerinatal HIV transmission has dramatically decreased with combination antiretroviral (ARV) regimens, but complications among HIV-exposed uninfected (HEU) children, such as microcephaly, warrant ongoing surveillance.MethodsWe evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a prospective cohort study conducted by the PHACS network at 22 US sites. Microcephaly was defined using 2000 CDC Growth z-scores for head circumference (HC) measured at 6–36 months of age (z-score <−2) and using Nellhaus standards (<2nd percentile) after age 3 (“SMARTT” criteria), or using Nellhaus standards across all ages. Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero ARV exposure and microcephaly status, adjusted for potential confounders. Sensitivity analyses were conducted. Neurodevelopmental functioning was compared between HEU children with vs. without microcephaly.ResultsAmong 3055 SMARTT participants enrolled as of April 2017 with a HC measurement over 5.1 years median follow-up (IQR = 3.0, 7.2), 159 (5.2%, 95% CI: 4.4–6.1%) had microcephaly identified by Nellhaus criteria and 70 (2.3%, 95% CI: 1.8–2.9%) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4.7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (aRR=2.02, 95% CI: 1.16, 3.51) and SMARTT criteria (adjusted RR = 2.56, 95% CI: 1.22, 5.37). These associations were more pronounced among children exposed to combination regimens of efavirenz which included zidovudine+lamivudine than those including tenofovir+emtricitabine (Figure 1). Associations of microcephaly with efavirenz persisted in several sensitivity analyses (Figure 2). Protective associations were observed for darunavir exposure (aRR = 0.50; 95% CI: 0.24, 1.00). HEU children with microcephaly had lower mean scores on neurodevelopmental assessments at ages 1 and 5 years and higher prevalence of impairment than those without microcephaly.ConclusionEfavirenz exposure during pregnancy was associated with a higher risk of microcephaly in infancy and childhood. These findings may support identification of alternatives to efavirenz as part of first-line ARV therapy. Disclosures All authors: No reported disclosures.

Birth Prevalence of Congenital Cytomegalovirus Infection in HIV-Exposed Uninfected Children in the Era of Combination Antiretroviral Therapy

To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200cells/μL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

2528. Inflammation and Plasma Selenium and Chromium in Ugandan Children Living with HIV

BackgroundSelenium deficiency has been reported to be associated with HIV disease progression and chromium deficiency with insulin resistance and hyperlipidemia. Here, we assessed selenium and chromium status in a cohort of Ugandan HIV+, HIV exposed uninfected (HEU) and HIV negative (HIV−) children and their associations with markers of systemic inflammation, immune activation, and gut integrity.MethodsThis is a cross-sectional study in HIV+, HEU and HIV unexposed uninfected (HIV-) children aged 2–10 years old enrolled in Uganda. HIV+ children were on stable ART with undetectable viral load. We measured plasma concentrations of selenium and chromium as well as markers of systemic inflammation, monocyte activation, gut integrity and insulin resistance (HOMA-IR).ResultsAmong HIV+ children (n = 57), 93% had viral load ≤ 20 copies/mL, mean CD4 was 34% and 77% were receiving a non-nucleotide reserve transcriptase regimen. Mean age of all participants was 7 years and 55% were girls. Mean selenium concentrations were higher in the HIV+ group (106 µg/L) compared with the HEU (84 µg/L) and HIV− (98 µg/L) groups (p . Mean chromium concentrations were 1 µg/L; 1 HIV+ child and 6 HEU children had chromium levels > 1 µg/L (p.ConclusionIn this cohort of HIV+ children on ART in Uganda, plasma selenium and chromium concentrations appear sufficient. Higher plasma selenium concentrations were associated with lower systemic inflammation and higher gut integrity markers. Although our findings do not support the use of selenium supplementation broadly for HIV-infected children in Uganda, further studies are warranted to assess the role of selenium supplements in attenuating heightened inflammation.Disclosures All authors: No reported disclosures.

Behavioral problems in perinatally HIV-infected young children with early antiretroviral therapy and HIV-exposed uninfected young children: prevalence and associated factors

ABSTRACTAlthough behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted. Behavioral problems were assessed with the Child Behavior Checklist (CBCL) at baseline and 12 months later among children aged 18–60 months old. The Patient Health Questionnaire-9 and the Parenting Styles & Dimensions Questionnaire identified primary caregivers’ symptoms of depression and parenting styles, respectively, at both visits. Chi-squared analyses were used to compare the prevalence of behavioral problems between groups. Factors associated with behavioral problems were analyzed by logistic regression. From 2016 to 2017, 121 children (41 PHIV and 80 HEU) were assessed with no significant differences in prevalence of Total, Internalizing, Externalizing, and Syndrome scales problems between PHIV and HEU at both visits (p > 0.5). Primary caregivers’ depression and lower education in addition to authoritarian and permissive parenting styles were significantly related to child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted.

2.64 A PSYCHOSOCIAL INTERVENTION IMPROVES SUSTAINED ATTENTION IN PRESCHOOL UGANDAN CHILDREN WITH HIV AND HIV-EXPOSED UNINFECTED (HEU) CHILDREN

HIV has been associated with cognitive impairments. Whether the impairments are the result of HIV or highly active antiretroviral therapy (HAART), toxicity remain to be identified. Findings have shown that HIV-exposed uninfected (HEU) children may show some cognitive impairment. Nonpharmacological methods of cognitive interventions strongly are advocated, particularly in resource-poor settings. Our study examined the benefits of a psychosocial training method called mediational intervention for sensitizing caregivers (MISC) on visual attention capacity among Ugandan preschool children living with HIV and HEU.

Differential expression of Fas receptors (CD95) and Fas ligands (CD95L) in HIV infected and exposed uninfected children in Cameroon versus unexposed children.

IntroductionThe number of HIV exposed uninfected (HEU) infants is increasing as vertical transmission is reducing. This subpopulation requires more investigations. This study aimed at comparing the expression level of soluble Fas receptors (FasR) and ligands (FasL) between HIV infected, HEU and unexposed children.MethodsEighty eight HIV-1infected, 86 HEU and 38 HIV unexposed children were recruited. Soluble FasR and FasL were measured in their plasma. Mann-Whitney U-Test was used to compare groups with 95% confidence. Spearman coefficient was used to test the correlation with CD4 and viral load (VL).ResultsOverall plasma levels of FasR were higher than that of FasL. The concentration of FasR and FasL were significantly higher in HIV-1 infected children in comparison to HEU and unexposed children. There was no difference in the plasma level of FasL in HIV infected compared to HEU children. A significant difference was observed between HIV infected children and HEU children (P=0.001) for the FasL. FasR were higher in both HIV infected and unexposed children compared to HEU children. There was a positive correlation (rs=+0.4; p=0.01) in ARV treated children between CD4 count and FasL concentration. Significant negative correlation (rs=-0.3; p=0.040) in ARV naïve children was observed between CD4 percentage and FasL. Significant and positive correlation (rs=+0.4; p=0.008) was observed between the VL and FasL in HIV infected, treated or not.ConclusionHEU children differ from HIV infected and unexposed children as the level of FasL/R expression is concerned. HEU should be considered different from HIV unexposed although exempt from virus as some immune dysfunctions have been reported among them.

Neurodevelopment of HIV-exposed uninfected children in South Africa: outcomes from an observational birth cohort study

SummaryBackgroundHIV infection is known to cause developmental delay, but the effects of HIV exposure without infection during pregnancy on child development are unclear. We compared the neurodevelopmental outcomes of HIV-exposed uninfected and HIV-unexposed children during their first 2 years of life.MethodsPregnant women (>18 years of age) at 20–28 weeks' gestation were enrolled into the Drakenstein Child Health cohort study while attending routine antenatal appointments at one of two peri-urban community-based clinics in Paarl, South Africa. Livebirths born to enrolled women during follow-up were included in the birth cohort. Mothers and infants received antenatal and postnatal HIV testing and antiretroviral therapy per local guidelines. Developmental assessments on the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), were done in a subgroup of infants at 6 months of age, and in the full cohort at 24 months of age, with assessors masked to HIV exposure status. Mean raw scores and the proportions of children categorised as having a delay (scores <–2 SDs from the reference mean) on BSID-III were compared between HIV-exposed uninfected and HIV-unexposed children.Findings1225 women were enrolled between March 5, 2012, and March 31, 2015. Of 1143 livebirths, 1065 (93%) children were in follow-up at 6 months and 1000 (87%) at 24 months. Two children were diagnosed with HIV infection between birth and 24-month follow-up and were excluded from the analysis. BSID-III assessments were done in 260 (24%) randomly selected children (61 HIV-exposed uninfected, 199 HIV-unexposed) at 6 months and in 732 (73%) children (168 HIV-exposed uninfected, 564 HIV-unexposed) at 24 months. All HIV-exposed uninfected children were exposed to antiretrovirals (88% to maternal triple antiretroviral therapy). BSID-III outcomes did not significantly differ between HIV-exposed uninfected and HIV-unexposed children at 6 months. At 24 months, HIV-exposed uninfected children scored lower than HIV-unexposed for receptive language (adjusted mean difference −1·03 [95% CI −1·69 to −0·37]) and expressive language (−1·17 [–2·09 to −0·24]), whereas adjusted differences in cognitive (−0·45 [–1·32 to 0·43]), fine motor (0·09 [–0·49 to 0·66]), and gross motor (−0·41 [–1·09 to 0·27]) domain scores between groups were not significant. Correspondingly, the proportions of HIV-exposed uninfected children with developmental delay were higher than those of HIV-unexposed children for receptive language (adjusted odds ratio 1·96 [95% CI 1·09 to 3·52]) and expressive language (2·14 [1·11 to 4·15]).InterpretationUninfected children exposed to maternal HIV infection and antiretroviral therapy have increased odds of receptive and expressive language delays at 2 years of age. Further long-term work is needed to understand developmental outcomes of HIV-exposed uninfected children, especially in regions such as sub-Saharan Africa that have a high prevalence of HIV exposure among children.FundingBill & Melinda Gates Foundation, SA Medical Research Council, Wellcome Trust.

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

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

Impact of in Utero and Breastfeeding Exposure to Tenofovir on Renal Function in HIV-exposed Uninfected Children

Impact of in Utero and Breastfeeding Exposure to Tenofovir on Renal Function in HIV-exposed Uninfected Children

In Utero Efavirenz Exposure and Neurodevelopmental Outcomes in HIV-exposed Uninfected Children in Botswana.

Minimal data exist related to neurodevelopment after in utero exposure to Efavirenz (EFV). We sought to compare neurodevelopmental outcomes in HIV-exposed/uninfected (HEU) children with in utero exposure to EFV-based triple antiretroviral treatment (ART) versus non-EFV-based ART, and to examine whether timing of initial EFV exposure is associated with neurodevelopment deficits. Women living with HIV who had received EFV-based ART during pregnancy and whose HEU newborn participated in a prior study were reconsented for their HEU toddler to undergo neurodevelopmental testing at 24 months old. We administered the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Developmental Milestones Checklist (DMC) and Profile of Social Emotional Development (PSED). We compared outcomes to previously-collected data from a cohort of 24-month-old HEU children with in utero exposure to non-EFV-based ART. Adjusted general linear models were used to compare mean outcomes. Our analysis included 493 HEU children (126 EFV-exposed, 367 EFV-unexposed). Adjusted mean scores for the EFV-exposed group were worse than the EFV-unexposed group on BSID-III Receptive Language (adjusted means = 21.5 vs. 22.5, P = 0.05), DMC Locomotor (30.7 vs. 32.0, P < 0.01) and Fine Motor scales (17.8 vs. 19.2, P < 0.01); and PSED (11.7 vs. 9.9, P = 0.02); but better on the DMC Language scale (17.6 vs. 16.5, P = 0.01). Earlier (vs. later) EFV exposure was associated with worse scores on the BSID-III Receptive Language scale (20.7 vs. 22.2, P = 0.02). HEU children exposed in utero to EFV-based ART may be at higher risk for neurodevelopmental and social-emotional deficits than HEU children exposed to non-EFV-based ART.

Antibody Responses Specific to Hepatitis B Virus Vaccine in Children Exposed InUtero to Antiretroviral Therapy

The use of antiretroviral (ARV) has been one of the most effective means of preventing vertical transmission of the human immunodeficiency virus (HIV) to exposed children born of HIV infected mothers. Nevertheless, responses to childhood vaccination against Hepatitis B virus (HBV) infections remain suboptimal in HIV exposed uninfected children irrespective of maternal ARV prophylaxis. In a cross-sectional study we have assessed the impact of in-utero exposure to ARV on paediatric HBV vaccination. Anti-HBV surface antigen specific antibodies (anti-HBs abs) were measured in plasma specimens from 44 healthy children unexposed to both HIV and ARV (HU), 25 HIV-exposed uninfected children naïve to intrauterine exposure to ARV (HEU.AR - ), 29 ARV and HIV-exposed uninfected children during pregnancy (HEU.ARV +), 50 children vertically infected with HIV but naïve to intrauterine exposure to ARV (HEI.ARV - ) and 22 children vertically infected with HIV with in utero exposure to ARV (HEI.ARV +). The protective seroconversion rate after childhood HBV vaccination (anti-HBs ≥10 mUI/ml) among HEU.ARV + children (58%) was significantly lower relative to both HEU.ARVc - (100%, P=0.0010) and the healthy unexposed children (92 %, P=0.0069). Similarly, HEI.ARV + children also had significantly lower anti-HBs IgM antibody responses when compared to both HU (p=0.0003) and HEI.ARV - (0.0001) children respectively. Thus in-utero exposure to ARV probably contributes in reducing HBV vaccine antibody response rate in both HIV exposed uninfected and vertically infected children after childhood vaccination. Nevertheless, the overall impact of ARV was to improve anti-HBs IgG responses in HIV infected children suggesting a possible role in immune reconstitution leading to improved IgG antibody responses.

Neurodevelopmental and behavioural outcomes of HIV-exposed uninfected and HIV-unexposed children at 2–3 years of age in Cape Town, South Africa

ABSTRACTSuccessful vertical HIV transmission prevention programmes (VTP) have resulted in an expanding population of HIV-exposed uninfected (HEU) infants whose growth, health and neurodevelopmental outcomes could have consequences for future resource allocation. We compared neurodevelopmental and behavioural outcomes in a prospective cohort of 2–3 year old HEU and HIV-unexposed uninfected (HU) children.Women living with and without HIV and their infants were enrolled within three days of birth from a low-risk midwife obstetric unit in Cape Town, South Africa during 2012 and 2013, under WHO Option A VTP guidelines. HIV-uninfected children aged 30–42 months were assessed using the Bayley scales of Infant Development-Third edition (BSID) and Strengths and Difficulties questionnaire (SDQ).Thirty-two HEU and 27 HU children (mean birth weight 3048g vs 3096g) were assessed. HEU children performed as well as HU children on BSID cognitive, language and motor domains. Mean scores fell within the low average range. Mothers of HEU children reported fewer conduct problems but stunting was associated with increased total difficulties on the SDQ.HEU and HU children’s performance on the BSID was similar. In this low-risk cohort, HIV exposure did not confer additional risk. Stunting was associated with increased behavioural problems irrespective of HIV exposure.