Sulfamethoxazole Levels in HIV-Exposed Uninfected Ugandan Children.
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ABSTRACT:
SUBMITTER: Kasule J
PROVIDER: S-EPMC6086194 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
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Sulfamethoxazole Levels in HIV-Exposed Uninfected Ugandan Children.
Kasule Jingo J Gabriel Erin E EE Anok Aggrey A Neal Jillian J Eastman Richard T RT Penzak Scott S Newell Kevin K Serwadda David D Duffy Patrick E PE Reynolds Steven J SJ Hobbs Charlotte V CV
The American journal of tropical medicine and hygiene 20180419 6
Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in HIV-uninfected, exposed (HUE) children variably reduces clinical malaria burden despite antifolate resistance, but data regarding achieved serum levels and adherence are lacking. Serum samples from 70 HUE children aged 3-12 months from Rakai, Uganda, enrolled in an observational study were assayed for random SMX levels using a colorimetric assay. Adherence with TMP-SMX prophylaxis data (yes/no) was also collected. Of 148 visits with concurre ...[more]
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Project description:BackgroundVery few studies consider the oral health status and quality of life in HIV-1 exposed uninfected (HEU) children. The aim of this study was to estimate the prevalence of caries in primary teeth and its oral health related quality of life impacts in HEU children compared to HIV-unexposed-uninfected (HUU) children, whilst adjusting for confounding covariates.MethodsThis study uses data from the Ugandan site of the ANRS 121741 PROMISE- PEP trial (ClinicalTrials.gov, number NCT00640263) conducted in 2009-2013 that recruited mothers with HIV-1 and their uninfected children. Of 244 HEU-children-caretaker pairs available at the end of the one-year trial, 166 were re-enrolled in the ANRS 12341 PROMISE-PEP M&S study at 5-7 years and 164 were included in this study. These were age and sex-matched with 181 HUU children-caretaker comparators. Caries experience was recorded using World Health Organization's Decayed, Missed and Filled teeth (dmft/DMFT) indices. The Early Childhood Oral health Impact Scale (ECOHIS) was used for assessment of oral health related quality of life. Mixed effects logistic regression was conducted with dmft and ECOHIS scores as outcomes and HIV-1 exposure status as the main exposure.ResultsForty-eight percent of HEU children and 60% of HUU had dmft> 0. Corresponding figures for ECOHIS> 0 were 12% of HEU and 22% of HUU. The crude analysis showed differences related to HIV-1 exposure in caries experience and oral health related quality of life. Mixed effect logistic regression analyses were not significant when adjusted for use of dental care and toothache. If caregivers' DMFT> 0, the adjusted odds ratio for caries experience (dmft> 0) was 1.6 (95% CI: 1.0-2.8) while if dmft> 0 the adjusted odds ratio for quality of life impacts (ECOHIS> 0) was 4.6 (95% CI: 2.0-10.6).ConclusionThe prevalence of untreated caries in primary teeth and quality of life impacts was high in this study population. HIV-1 exposed uninfected children were not more likely than HUU children to experience dental caries or have impaired oral health related quality of life. Given the global expansion of the HEU child population, the present findings indicating no adverse effect of pre- and post-natal HIV-1 exposure on caries in deciduous teeth are reassuring.
| S-EPMC7106612 | biostudies-literature
Project description:ObjectiveTo report vigilance attention outcomes from a cluster randomized controlled trial of early childhood development caregiver training for perinatally HIV-exposed/uninfected preschool-age children in rural Uganda. The Early Childhood Vigilance Test (ECVT) provides a webcam recording of proportion of time a child views an animation periodically moving across a computer screen.Study designSixty mothers/caregivers received biweekly year-long training sessions of the Mediational Intervention for Sensitizing Caregivers (MISC), and 59 mothers received biweekly training about nutrition, hygiene, and health care. Children were tested for attention at baseline, 6 months, and 12 months with the ECVT, in terms of proportion of time spent viewing a 6-minute animation of animals greeting the child and moving across the computer monitor screen. Time viewing the animation were scored by trained observers using ProCoder program for webcam scoring of proportion of time the child faced the animation. Mixed-effects modeling was used to compare ECVT outcomes for the 2 intervention groups.ResultsUnadjusted and adjusted (for age, sex, height, and ECVT at baseline) group differences on ECVT significantly favored the MISC arm at 6 months (P = .03; 95% CI (0.01, 0.11), effect size = 0.46) but not at 12 months. Both groups made significant gains in sustained attention across the year-long intervention (P = .021) with no significant interaction effects between time and treatment arms or sex.ConclusionsCaregiver early childhood development training enhanced attention in at-risk Ugandan children, which can be foundational to improved working memory and learning, and perhaps related to previous language benefits reported for this cohort.Trial registrationClinicaltrials.gov: NCT00889395.
| S-EPMC8316287 | biostudies-literature
Project description:BACKGROUND:HIV-exposed uninfected (HEU) children experience increased mortality compared with their HIV-unexposed uninfected (HUU) peers. It is unclear whether HEU children are also at increased risk for undernutrition, a modifiable risk factor for mortality. METHODS:We conducted a cross-sectional, population-based survey of children <5 years of age in 5 health districts in Botswana. Linear mixed-effects models were used to assess continuous outcomes, and generalized estimating equations were used to estimate relative risks of stunting, wasting, and underweight between HEU (n = 396) and HUU (n = 1109) children. Secondary analyses examined potential mediation by low birth weight. RESULTS:The association between maternal HIV exposure and child stunting varied significantly by child age (P < 0.01). HEU children <1 and ?2 years of age had 1.85 [95% confidence interval (CI): 1.03 to 3.31; P = 0.04] and 1.41 (95% CI: 1.06 to 1.88; P = 0.02) times the risk of stunting compared with HUU children after multivariate adjustment, respectively. During the period of 1-2 years of age, when breastfeeding cessation occurred among HUU children, HUU children had increased risk of stunting compared with HEU children who were predominantly formula fed (relative risk: 1.56; 95% CI: 1.05 to 2.32; P = 0.03). A mediation analysis estimated that 67% of the excess risk of stunting among HEU children ?2 years was attributable to low birth weight (P = 0.02). There was no difference in risk of wasting or underweight. CONCLUSION:HEU children are at increased risk of stunting compared with their HUU peers; however, interventions to increase birth weight may significantly ameliorate this excess risk. Interventions to support optimal growth during weaning are needed for all breast-fed children.
| S-EPMC5023451 | biostudies-literature
Project description:We sought to determine if HIV-exposed uninfected (HEU) children had worse neurodevelopmental outcomes at 24 months compared with HIV-unexposed uninfected (HUU) children in Botswana. HIV-infected and uninfected mothers enrolled in a prospective observational study ("Tshipidi") in Botswana from May 2010 to July 2012. Child neurodevelopment was assessed at 24 months with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III: cognitive, gross motor, fine motor, expressive language, and receptive language domains) and the Development Milestones Checklist (DMC), a caregiver-completed questionnaire (locomotor, fine motor, language and personal-social domains). We used linear regression models to estimate the association of in-utero HIV exposure with neurodevelopment, adjusting for socioeconomic and maternal health characteristics. We evaluated 670 children (313 HEU, 357 HUU) with ≥1 valid Bayley-III domain assessed and 723 children (337 HEU, 386 HUU) with a DMC. Among the 337 HEU children with either assessment, 122 (36%) were exposed in utero to maternal 3-drug antiretroviral treatment and 214 (64%) to zidovudine. Almost all HUU children (99.5%) breastfed, compared with only 9% of HEU children. No domain score was significantly lower among HEU children in adjusted analyses. Bayley-III cognitive and DMC personal-social domain scores were significantly higher in HEU children than in HUU children, but differences were small. HEU children performed equally well on neurodevelopmental assessments at 24 months of age compared with HUU children. Given the global expansion of the HEU population, results suggesting no adverse impact of in-utero HIV and antiretroviral exposure on early neurodevelopment are reassuring.
| S-EPMC5613819 | biostudies-literature
Project description:OBJECTIVE:Early childhood development programs typically combine healthy nutrition and cognitive stimulation in an integrated model. We separately delivered these 2 components in a cluster-randomized controlled trial to evaluate their comparative effectiveness in promoting healthy child development and caregiver mental health. This is the first study to do so for HIV-affected children and their infected mothers. METHODS:Two hundred twenty-one HIV-exposed but uninfected child (2-3 years old) and caregiver dyads in 18 geographic clusters in Eastern Uganda were randomized by cluster to receive biweekly individualized sessions of either (1) Mediational Intervention for Sensitizing Caregivers (MISC) training emphasizing cognitive stimulation or (2) Uganda Community Based Association for Child Welfare (UCOBAC) program that delivered health and nutrition training. Children were evaluated at baseline, 6 months, 1 year (training conclusion), and 1-year posttraining with the Mullen Scales of Early Learning (MSEL), the Color-Object Association Test for memory, the Early Childhood Vigilance Test of attention, and the Behavior Rating Inventory of Executive Function (BRIEF-parent). The Caldwell Home Observation for the Measurement of the Environment (HOME) was completed by observers to gauge caregiving quality after training. Caregiver depression/anxiety (Hopkins Symptom Checklist-25) and functionality (list of activities of daily living) were also evaluated. Data collectors were blinded to trial arm assignment. RESULTS:Mediational Intervention for Sensitizing Caregivers resulted in significantly better quality of caregiving compared with UCOBAC midintervention with an adjusted mean difference (MadjDiff) of 2.34 (95% confidence interval [CI]: 1.54-3.15, p < .01), postintervention (MadjDiff = 2.43, 95% CI: 1.61-3.25, p < .01), and at 1-year follow-up (MadjDiff = 2.07, 95% CI: 1.23-2.90, p < .01). MISC caregivers reported more problems on the BRIEF for their child at 1-year posttraining only (p < .01). Caregiving quality (HOME) was significantly correlated with MSEL composite performance 1-year posttraining for both the MISC and the UCOBAC trial arms. Likewise, physical growth was significantly related to child development outcomes even though it did not differ between trial arms. CONCLUSION:Even though MISC demonstrated an advantage of improving caregiving quality, it did not produce better child cognitive outcomes compared with health and nutrition training. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01640561.
| S-EPMC5668186 | biostudies-literature
Project description:ObjectiveWith increasing maternal antiretroviral treatment (ART), the number of children newly infected with HIV has declined. However, the possible increased mortality in the large number of HIV-exposed, uninfected (HEU) children may be of concern. We quantified mortality risks among HEU children and reviewed associated factors.MethodsSystematic search of electronic databases (PubMed, Scopus). We included all studies reporting mortality of HEU children to age 60 months and associated factors. Relative risk of mortality between HEU and HIV-unexposed, uninfected (HUU) children was extracted where relevant. Inverse variance methods were used to adjust for study size. Random-effects models were fitted to obtain pooled estimates.ResultsA total of 14 studies were included in the meta-analysis and 13 in the review of associated factors. The pooled cumulative mortality in HEU children was 5.5% (95% CI: 4.0-7.2; I(2) = 94%) at 12 months (11 studies) and 11.0% (95% CI: 7.6-15.0; I(2) = 93%) at 24 months (four studies). The pooled risk ratios for the mortality in HEU children compared to HUU children in the same setting were 1.9 (95% CI: 0.9-3.8; I(2) = 93%) at 12 months (four studies) and 2.4 (95% CI: 1.1-5.1; I(2) = 93%) at 24 months (three studies).ConclusionCompared to HUU children, mortality risk in HEU children was about double at both age points, although the association was not statistically significant at 12 months. Interpretation of the pooled estimates is confounded by considerable heterogeneity between studies. Further research is needed to characterise the impact of maternal death and breastfeeding on the survival of HEU infants in the context of maternal ART, where current evidence is limited.
| S-EPMC5021152 | biostudies-literature
Project description:OBJECTIVES:To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures. DESIGN:Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV and PHEU youth. METHODS:Serum samples were analyzed among 402 youth in the PHACS Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs-cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide (NT-proBNP, a myocardial stress marker), and inflammatory markers [high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-? (TNF-?), and soluble TNF receptor II (sTNF-RII)]. Echocardiograms were centrally measured and parameters converted to z cores to account for differences in age and body size. RESULTS:Compared with PHEU (N?=?156), PHIV youth (N?=?246) more often had detectable hs-cTnT and higher levels of sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with higher left ventricular (LV) wall stress and lower LV function and LV mass in the two groups. Among PHIV youth, the biomarkers were more strongly associated with current rather than historical immunologic and virologic status. CONCLUSION:PHEU and PHIV have modest, significant differences in serum levels of specific inflammatory and active myocardial injury biomarkers. Higher biomarker levels were associated with lower LV mass and shifts in LV structure. Further study is warranted on the longitudinal role of cardiac and inflammatory biomarkers for targeting interventions among PHIV and PHEU youth.
| S-EPMC6387791 | biostudies-literature
Project description:OBJECTIVES:To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART). DESIGN:Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother-infant pairs through 12-18 months postpartum. SETTING:Peri-urban community, Cape Town, South Africa. PARTICIPANTS:HEU (n = 215) and HIV-unexposed (n = 306) children. MAIN OUTCOME MEASURES:Cognitive, motor and language development at median 13 (interquartile range 12-14) months of age: continuous and dichotomous Bayley Scales of Infant and Toddler Development Third Edition (delay defined as composite score <85). RESULTS:Incidence of preterm delivery (<37 weeks) was similar among HEU and HIV-unexposed children (11 vs. 9%, P = 0.31; median gestation 39 weeks); 48% were boys. Median breastfeeding duration was shorter among HEU vs. HIV-unexposed children (6 vs. 10 months). All HIV-infected mothers initiated lifelong ART (tenofovir-emtricitabine-efavirenz) antenatally. HEU (vs. HIV-unexposed) children had higher odds of cognitive delay [odds ratio (OR) 2.28 (95% confidence interval (CI) 1.13-4.60)] and motor delay [OR 2.10 (95% CI 1.03-4.28)], but not language delay, in crude and adjusted analysis. Preterm delivery modified this relationship for motor development: compared with term HIV-unexposed children, term HEU children had similar odds of delay, preterm HIV-unexposed children had five-fold increased odds of delay (adjusted OR 4.73, 95% CI 1.32; 16.91) and preterm HEU children, 16-fold increased odds of delay (adjusted OR 16.35, 95% CI 5.19; 51.54). CONCLUSION:Young HEU children may be at increased risk for cognitive and motor delay despite universal maternal ART and breastfeeding; those born preterm may be particularly vulnerable.
| S-EPMC6341164 | biostudies-literature
Project description:BackgroundCytomegalovirus (CMV) viremia is associated with mortality in severely ill immunocompetent adults and hospitalized children with HIV (CWH). We measured CMV viremia in HIV-exposed and -unexposed Kenyan children aged 1-59 months discharged from hospital and determined its relationship with postdischarge mortality.MethodsCMV DNA levels were measured in plasma from 1024 children (97 of which were HIV exposed uninfected [HEU], and 15 CWH). Poisson and Cox proportional hazards regression models were used to identify correlates of CMV viremia ≥ 1000 IU/mL
and estimate associations with 6-month mortality, respectively.ResultsCMV viremia was detected in 31% of children, with levels ≥ 1000 IU/mL in 5.8%. HIV infection, age < 2 years, breastfeeding, and midupper arm circumference < 12.5 cm were associated with CMV viremia ≥ 1000 IU/mL. Among HEU children, CMV ≥ 1000 IU/mL (hazard ratio [HR] = 32.0; 95% confidence interval [CI], 2.9-354.0; P = .005) and each 1-log increase in CMV viral load (HR = 5.04; 95% CI, 1.7-14.6; P = .003) were associated with increased risk of mortality. CMV viremia was not significantly associated with mortality in HIV-unexposed children.ConclusionsCMV levels at hospital postdischarge predict increased risk of 6-month mortality in Kenyan HEU children. CMV suppression may be a novel target to reduce mortality in HEU children.Clinical trial registrationNCT02414399.
| S-EPMC9624454 | biostudies-literature
Project description:ObjectivePrevious 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.DesignMeta-analysis.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.
| S-EPMC8214449 | biostudies-literature