Background:Complete follow up is an essential component of observational cohorts irrespective of the type of disease.Objectives:To describe five years follow up of mother and child pairs on a PMTCT program, highlighting loss to follow up (LTFU) and mortality (attrition).Study Design:A cohort of pregnant women was enrolled from the national PMTCT program at 36 weeks gestational age attending three peri urban clinics around Harare offering maternal and child health services. Mother-infant pairs were followed up from birth and twice yearly for five years.Results:A total of 479 HIV infected and 571 HIV negative pregnant women were enrolled, 445(92.9%) and 495(86.6%) were followed up whereas 14(3.0%) and 3(0.5%) died in the 1st year respectively; RR (95%CI) 5.3(1.5-18.7). At five years 227(56.7%) HIV infected and 239(41.0%) HIV negative mothers turned up, whereas mortality rates were 34 and 7 per 100 person years respectively. Birth information was recorded for 401(83.7%) HIV exposed and 441(77.2%) unexposed infants, 247(51.6%) and 232(40.6) turned up in the first year whilst mortality was 58(12.9%) and 22(4.4%) respectively, RR (95%CI) 3.2(2.0-5.4). At five years 210(57.5%) HIV exposed and 239(44.3%) unexposed infants were seen, whilst mortality rates were 53 per 1000 and 15 per 1 000 person years respectively. Mortality rate for HIV infected children was 112 compared to 21 per 1 000 person years for the exposed but uninfected.Conclusion:HIV infected mothers and their children succumbed to mortality whereas the HIV negatives were LTFU. Mortality rates and LTFU are high within PMTCT program.

With long-term survival of children infected with HIV, information on cognitive function at school age is needed. To determine cognitive function among 6- to 8 year-old children exposed to HIV and to assess factors associated with cognitive impairment, we conducted a cross-sectional study from October 2010 to December 2011 among children whose mothers participated in a national HIV prevention program in Harare. Cognitive function was assessed using the McCarthy Scales of Children's Abilities (MSCA). Of the 306 assessed children, 32 (10%) were HIV infected, 121 (40%) exposed uninfected, and 153 (50%) unexposed uninfected. The mean (SD) General Cognitive Index for the whole study group was 82 (15). An overall of 49 (16%) out of the 306 children had cognitive impairment with no difference in general cognitive function among the three groups. Children with HIV infection scored lowest in perceptual performance domain, p = .028. Unemployed caregivers, child orphanhood and undernutrition were associated with impaired cognitive performance in univariate analysis. In multivariate analysis, caregiver unemployment status remained a factor associated with cognitive impairment with an ODDS ratio of 2.1 (95% CI 1.03-3.36). In a cohort of 6- to 8-year-olds, HIV infection did not show evidence of significant difference in general cognitive function. Children infected with HIV had major deficits in perceptive performance. Lower socioeconomic status was associated with cognitive impairment. In resource-constrained settings, strategies aimed at poverty alleviation and good nutritional management should complement early infant diagnosis and treatment of HIV in order to optimize neurocognitive potential.

Objective: To determine immune-metabolic dysregulation in children born to women living with HIV. Methods: Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed. Results: Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length. Conclusion: These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.

Background Human immunodeficiency virus (HIV) severely damages the epithelial cells of the gut lining leading to an inflamed leaky gut, translocation of microbial products, and dysbiosis resulting in systemic immune activation. Also, microbiota composition and maternal gut function can be altered in pregnancy through changes in the immune system and intestinal physiology. The aim of this study was to investigate the gut microbiota in HIV-infected and HIV-uninfected pregnant women and to compare and identify the association between gut microbial composition and adverse birth outcomes. Results A total of 94 pregnant women (35 HIV-infected and 59 HIV-uninfected controls) were recruited in Harare from 4 polyclinics serving populations with relatively poor socioeconomic status. Women were of a median age of 28 years (interquartile range, IQR: 22.3–32.0) and 55% of women were 35 weeks gestational age at enrolment (median 35.0 weeks, IQR: 32.5–37.2). Microbiota profiling in these participants showed that species richness was significantly lower in the HIV-infected pregnant women compared to their HIV-uninfected peers and significant differences in β-diversity using Bray–Curtis dissimilarity were observed. In contrast, there was no significant difference in α-diversity between immune-compromised (CD4+  < 350 cells/µL) and immune-competent HIV-infected women (CD4+  ≥ 350 cells/µL) even after stratification by viral load suppression. HIV infection was significantly associated with a reduced abundance of Clostridium, Turicibacter, Ruminococcus, Parabacteroides, Bacteroides, Bifidobacterium, Treponema, Oscillospira, and Faecalibacterium and a higher abundance of Actinomyces, and Succinivibrio. Low infant birth weight (< 2500 g) was significantly associated with high abundances of the phylum Spirochaetes, the families Spirochaeteceae, Veillonellaceae, and the genus Treponema. Conclusion The results reported here show that the species richness and taxonomy composition of the gut microbiota is altered in HIV-infected pregnant women, possibly reflecting intestinal dysbiosis. Some of these taxa were also associated with low infant birth weight.

Introduction Despite being a leading infectious cause of childhood disability globally, testing for cytomegalovirus (CMV) infections in pregnancy is generally not done in Sub-Sahara Africa (SSA), where breastfeeding practice is almost universal. Whilst CMV and human immunodeficiency virus (HIV) are both endemic in SSA, the relationship between antenatal plasma CMV-DNA, HIV-1-RNA levels and HIV-1-mother to child transmission (MTCT) including pregnancy outcomes remains poorly described. Methods Pregnant women at least 20 weeks’ gestational age at enrolment were recruited from relatively poor high-density suburbs in Harare, Zimbabwe. Mother-infant dyads were followed up until 6 months postpartum. In a case–control study design, we tested antenatal plasma CMV-DNA levels in all 11 HIV-1 transmitting mothers, as well as randomly selected HIV-infected but non-transmitting mothers and HIV-uninfected controls. CMV-DNA was detected and quantified using polymerase chain reaction (PCR) technique. Antenatal plasma HIV-1-RNA load was quantified by reverse transcriptase PCR. Infants’ HIV-1 infection was detected using qualitative proviral DNA-PCR. Predictive value of antenatal plasma CMV-DNAemia (CMV-DNA of > 50 copies/mL) for HIV-1-MTCT was analyzed in univariate and multivariate regression analyses. Associations of CMV-DNAemia with HIV-1-RNA levels and pregnancy outcomes were also explored. Results CMV-DNAemia data were available for 11 HIV-1 transmitting mothers, 120 HIV-infected but non-transmitting controls and 46 HIV-uninfected mothers. In a multivariate logistic regression model, we found a significant association between CMV-DNAemia of > 50 copies/mL and HIV-1 vertical transmission (p = 0.035). There was no difference in frequencies of detectable CMV-DNAemia between HIV-infected and -uninfected pregnant women (p = 0.841). However, CMV-DNA levels were higher in immunosuppressed HIV-infected pregnant women, CD4 < 200 cells/µL (p = 0.018). Non-significant associations of more preterm births (< 37 weeks, p = 0.063), and generally lower birth weights (< 2500 g, p = 0.450) were observed in infants born of HIV-infected mothers with CMV-DNAemia. Furthermore, in a multivariate analysis of HIV-infected but non-transmitting mothers, CMV-DNAemia of > 50 copies/mL correlated significantly with antenatal plasma HIV-1-RNA load (p = 0.002). Conclusion Antenatal plasma CMV-DNA of > 50 copies/mL may be an independent risk factor for HIV-1-MTCT and higher plasma HIV-1-RNA load, raising the possibility that controlling antenatal CMV-DNAemia might improve infant health outcomes. Further studies with larger sample sizes are warranted to confirm our findings.