Multi-modal analysis of inflammation as a potential mediator of depressive symptoms in young people with HIV: The GOLD depression study.

People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms.

Feasibility Study of a Powder-Based Supplement Intervention for a future Synbiotic Trial in Breastfed Children from South Africa.

Background: Children who are HIV-exposed uninfected (HEU), i.e., born to mothers living with HIV despite not acquiring HIV infection themselves, have increased morbidity and mortality.

Use of an ETEC Proteome Microarray to Evaluate Cross-Reactivity of ETVAX Vaccine-Induced IgG Antibodies in Zambian Children.

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.

Mitigating Infectious morbidity and Growth deficits in HIV-exposed uninfected infanTs with human Milk Oligosaccharide (MIGH-T MO): a randomised trial protocol.

Introduction: Children 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.

HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load.

There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 subtype C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment-naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function.

Peripheral-blood cytopenia, an early indicator of inborn errors of immunity.

Inborn errors of immunity (IEI) are inherited monogenic disorders resulting in defective immune response. Non-infectious presentations are increasingly more apparent. Widely available, cost-effective early indicators are needed.

HIV-1 subtype C Tat exon-1 amino acid residue 24K is a signature for neurocognitive impairment.

Variation and differential selection pressures on Tat genes have been shown to alter the biological function of the protein, resulting in pathological consequences in a number of organs including the brain. We evaluated the impact of genetic variation and selection pressure on 147 HIV-1 subtype C Tat exon 1 sequences from monocyte-depleted peripheral lymphocytes on clinical diagnosis of neurocognitive impairment. Genetic analyses identified two signature amino acid residues, lysine at codon 24 (24K) with a frequency of 43.

Mendelian susceptibility to mycobacterial disease in tuberculosis-hyperendemic South Africa.

Background: Severe infections in the absence of secondary immunodeficiency can alert clinicians to single-gene inborn errors of immunity/primary immunodeficiency disorders (PIDDs). Mendelian susceptibility to mycobacterial disease (MSMD) is characterised by selective susceptibility to mycobacterial infections due to inborn errors in the interleukin 12-interferon gamma pathway. The South African (SA) burden of hyperendemic tuberculosis (TB) infection provides an interesting context for the study of MSMD.

Plasma Cytokine Biomarker Cutoff Values for HIV-Associated Neurocognitive Impairment in Adults.

Diagnosing HIV-associated neurocognitive impairment in most high-burden, but resource-constrained, settings is difficult due to the unavailability of specialist neurologists and neuropsychologists in primary health care centers. New tests that are easy to perform, based on virological and host immune response biomarkers, may be valuable in the diagnosis of HIV-associated neurocognitive disorder. The receiver operator characteristic curve analysis was used to investigate the diagnostic accuracy of threshold/cutoff concentrations for the peripheral lymphocyte proviral load and plasma biomarkers as diagnostic candidates for neurocognitive impairment in 133 HIV-infected individuals, using global deficit scores as the clinical gold standard.

Phenotypic and immune functional profiling of patients with suspected Mendelian Susceptibility to Mycobacterial Disease in South Africa.

Background: Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a primary immunodeficiency (PID) characterised by a predisposition to infection by weakly-pathogenic mycobacteria. In countries with a high prevalence of tuberculosis (TB), individuals with MSMD are also prone to infections by Mycobacterium tuberculosis. Several MSMD-associated genes have been described, all resulting in a disruption of IL-12 and IFN-γ cytokine axis, which is essential for control of mycobacterial infections.

Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting.

Primary immunodeficiency disorders (PIDs) are inborn errors of immunity (IEI) that cause immune system impairment. To date, more than 400 single-gene IEI have been well defined. The advent of next generation sequencing (NGS) technologies has improved clinical diagnosis and allowed for discovery of novel genes and variants associated with IEI.

Expansion of GARP-Expressing CD4CD25FoxP3 T Cells and SATB1 Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa.

Although antiretroviral treatment lowers the burden of human immunodeficiency virus (HIV)-related disease, it does not always result in immunological recovery. This manifests as persistent chronic inflammation, immune activation or exhaustion that can promote the onset of co-morbidities. As the exact function of regulatory T (Treg) cells in HIV remains unclear, this cross-sectional study investigated three expression markers (Forkhead box protein P3 [FOXP3], glycoprotein A repetitions predominant [GARP], special AT-rich sequence binding protein 1 [SATB1]) and compared their expansion between CD4CD25 and CD4CD25 T cells.

Plasma Cytokine Levels As Predictors of Global and Domain-Specific Human Immunodeficiency Virus-Associated Neurocognitive Impairment in Treatment-Naive Individuals.

Central nervous system dysfunction, associated with human immunodeficiency virus (HIV) infection, remains a significant clinical concern, affecting at least 50% of infected people. Imbalances in cytokine expression levels have been linked to HIV-associated neurocognitive disorders. The aim of this study was to evaluate plasma cytokine levels as predictor neurocognitive impairment in HIV infection using a multiplex profiling kit.

Impact of Plasma IP-10/CXCL10 and RANTES/CCL5 Levels on Neurocognitive Function in HIV Treatment-Naive Patients.

Immune activation, which is accompanied by the production of proinflammatory cytokines, is a strong predictor of disease progression in HIV infection. Inflammation is critical in neuronal damage linked to HIV-associated neurocognitive disorders. We examined the relationship between plasma cytokine levels and deficits in neurocognitive function.

Monocyte/Macrophage-Mediated Innate Immunity in HIV-1 Infection: From Early Response to Late Dysregulation and Links to Cardiovascular Diseases Onset.

Although monocytes and macrophages are key mediators of the innate immune system, the focus has largely been on the role of the adaptive immune system in the context of human immunodeficiency virus (HIV) infection. Thus more attention and research work regarding the innate immune system-especially the role of monocytes and macrophages during early HIV-1 infection-is required. Blood monocytes and tissue macrophages are both susceptible targets of HIV-1 infection, and the early host response can determine whether the nature of the infection becomes pathogenic or not.

Peripheral blood lymphocyte proviral DNA predicts neurocognitive impairment in clade C HIV.

It is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region.

Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV.

Background: Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age at presentation and survival of HCC.

Identification of a novel WAS mutation in a South African patient presenting with atypical Wiskott-Aldrich syndrome: a case report.

Background: The X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in the WAS gene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes.

HIV and cardiovascular diseases risk: exploring the interplay between T-cell activation, coagulation, monocyte subsets, and lipid subclass alterations.

Although rollout of combined antiretroviral treatment (cART) has blunted human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) onset, there is increased development of cardiovascular diseases (CVDs) in HIV-infected individuals. While most HIV-infected individuals on cART achieve viral suppression, this may not necessarily result in complete immunological recovery. This study therefore evaluated T-cell-mediated changes and coagulation markers in HIV-positive individuals to ascertain their potential to increase CVD risk.

HBV and HIV viral load but not microbial translocation or immune activation are associated with liver fibrosis among patients in South Africa.

Background: Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection.

Methods: We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa.

Clinical Relevance of Total HIV DNA in Peripheral Blood Mononuclear Cell Compartments as a Biomarker of HIV-Associated Neurocognitive Disorders (HAND).

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.

Patterns of prevalent HPV and STI co-infections and associated factors among HIV-negative young Western Cape, South African women: the EVRI trial.

Objective: To estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial.

Methods: HIV-negative women aged 16-24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68).