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IntroductionChildren who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls.Methods and analysisOne hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4-24 weeks and 4-48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention.Ethics and disseminationEthical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications.Trial registration numberClinicalTrials.gov Identifier: NCT05282485. SANCTR ID number: DOH-27-122021-6543.

Developing a broadly protective vaccine covering most ETEC variants has been elusive. The most clinically advanced candidate yet is an oral inactivated ETEC vaccine (ETVAX®). We report on the use of a proteome microarray for the assessment of cross-reactivity of anti-ETVAX® IgG antibodies against over 4000 ETEC antigens and proteins. We evaluated 40 (pre-and post-vaccination) plasma samples from 20 Zambian children aged 10–23 months that participated in a phase 1 trial investigating the safety, tolerability, and immunogenicity of ETVAX® adjuvanted with dmLT. Pre-vaccination samples revealed high IgG responses to a variety of ETEC proteins including classical ETEC antigens (CFs and LT) and non-classical antigens. Post-vaccination reactivity to CFA/I, CS3, CS6, and LTB was stronger than baseline among the vaccinated compared to the placebo group. Interestingly, we noted significantly high post-vaccination responses to three non-vaccine ETEC proteins: CS4, CS14, and PCF071 (p = 0.043, p = 0.028, and p = 0.00039, respectively), suggestive of cross-reactive responses to CFA/I. However, similar responses were observed in the placebo group, indicating the need for larger studies. We conclude that the ETEC microarray is a useful tool for investigating antibody responses to numerous antigens, especially because it may not be practicable to include all antigens in a single vaccine. [ABSTRACT FROM AUTHOR]

A study was conducted on African people to analyze the stromal cell derived factor 1 (SDF1)-3'A single nucleotide polymorphism (SNP) and performed mutation screening for polymorphic markers in the chemokine receptor 4 (CXCR4) gene to determine existence of significant associations with susceptibility to HIV-1 infection. Comprehensive mutation analysis of the CXCR4 gene confirmed a high degree of genetic conservation within the coding region of African ancient populations.

The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. It is hypothesized that the critical events initiating this condition occur outside the brain, particularly in the peripheral blood. Diagnoses of HIV-induced neurocognitive disorders largely rely on neuropsychometric assessments, which are not precise. Total HIV DNA in the peripheral blood mononuclear cells (PBMCs), quantified by PCR, correlate with disease progression, which is a promising biomarker to predict HAND. Numerous PCR assays for HIV DNA in cell compartments are prone to variation due to the lack of standardization and, therefore, their utility in predicting HAND produced different outcomes. This review evaluates the clinical relevance of total HIV DNA in circulating mononuclear cells using different published quantitative PCR (qPCR) protocols. The rationale is to shed light on the most appropriate assays and sample types used to accurately quantify HIVDNAload, which predicts severity of neurocognitive impairment. The role of monocytes as a vehicle for trafficking HIV into the CNS makes it the most suitable sample for determining a HAND associated reservoir. Studies have also shown significant associations between monocyte HIV DNA levels with markers of neurodamage. However, qPCR assays using PBMCs are cheaper and available commercially, thus could be beneficial in clinical settings. There is need, however, to standardise DNA extraction, normalisation and limit of detection. [ABSTRACT FROM AUTHOR]

The effective role of antiretroviral (ARV) therapy in the regulation of CD4 T cell subset distribution, coreceptor expression, and activation status in individuals with chronic HIV also presenting with active pulmonary TB is not clearly understood. A cross-sectional analysis was performed on a total of 137 South African individuals. CCR5, CXCR4, and CD38 expression of CD4 T cell subsets in HIV-infected individuals with and without active pulmonary tuberculosis (TB) disease, pre- and post-ARV therapy, were determined by flow cytometry. In treatment-naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 in TB/HIV coinfection as compared to HIV infection alone despite the overall percentage of CD4 T cells expressing CCR5 being reduced. Total CD38+ CD4 T cells were not significantly increased in either group; however, mean CD38 fluorescence was significantly higher in the context of TB infection. HIV/TB-coinfected individuals also displayed an increased percentage of activated (CD38+) CCR5+ CD4 T cells as compared to HIV patients alone. The naive CD4 T cell subset was depleted similarly in both HIV and HIV/TB groups. Only the HIV treatment group and not the TB-coinfected treatment group showed significantly decreased activated CCR5+ CD4 T cells, an increased percentage of naive T cells, and a decreased percentage of antigen-experienced T cells. This study highlighted an association of TB disease with immune activation, particularly of the CCR5+ CD4 T cell subset in HIV infection and the differential impact of ARV treatment. Further studies are needed to understand how TB coinfection confounds normal responses to ARV. [ABSTRACT FROM AUTHOR]

Within-population genetic diversity is greatest within Africa, while between-population genetic diversity is directly proportional to geographic distance. The most divergent contemporary human populations include the click-speaking forager peoples of southern Africa, broadly defined as Khoesan. Both intra- (Bantu expansion) and inter-continental migration (European-driven colonization) have resulted in complex patterns of admixture between ancient geographically isolated Khoesan and more recently diverged populations. Using gender-specific analysis and almost 1 million autosomal markers, we determine the significance of estimated ancestral contributions that have shaped five contemporary southern African populations in a cohort of 103 individuals. Limited by lack of available data for homogenous Khoesan representation, we identify the Ju/'hoan (n = 19) as a distinct early diverging human lineage with little to no significant non- Khoesan contribution. In contrast to the Ju/'hoan, we identify ancient signatures of Khoesan and Bantu unions resulting in significant Khoesan- and Bantu-derived contributions to the Southern Bantu amaXhosa (n = 15) and Khoesan !Xun (n = 14), respectively. Our data further suggests that contemporary !Xun represent distinct Khoesan prehistories. Khoesan assimilation with European settlement at the most southern tip of Africa resulted in significant ancestral Khoesan contributions to the Coloured (n = 25) and Baster (n = 30) populations. The latter populations were further impacted by 170 years of East Indian slave trade and intra-continental migrations resulting in a complex pattern of genetic variation (admixture). The populations of southern Africa provide a unique opportunity to investigate the genomic variability from some of the oldest human lineages to the implications of complex admixture patterns including ancient and recently diverged human lineages. [ABSTRACT FROM AUTHOR]

An abstract of the article "Monocytes in Chronic HIV-1 Infection: Putative Gut Homing Markers and their Relationship with Immune Activation" by Karmistha Poovan, Hayley Ipp and Richard H. Glashoff is presented.