👤 Christopher B Rupert

The association of mucosal shedding of human simplex virus (HSV)-2, Kaposi's sarcoma-associated herpesvirus (KSHV) and cytomegalovirus (CMV) after antiretroviral therapy (ART) initiation in women-living-with-HIV (WLWH) with systemic inflammation is unclear. We recruited 187 ART-naive adult WLWH in south-central Uganda. HSV-1, HSV-2, CMV, and Varicella Zoster Virus (VZV) in vaginal secretions and Kaposi's sarcoma-associated herpesvirus (KSHV) in oral swabs were quantified by PCR. Plasma biomarkers of systemic inflammation were measured by ELISA or electrochemiluminescence before and after ART initiation (weeks 8, 12, and 24). Participants had a baseline median age of 28 years and CD4 count of 413 cells/μL. Viral shedding rates were similar for all tested viruses between baseline and post-ART timepoints in the overall study population. CMV shedding significantly increased from a baseline rate of 53% to 77% at week 4 visit ( Although ART initiation was not associated with increased herpesvirus shedding overall, CMV shedding increased in women with advanced HIV-1. The association of mucosal shedding of CMV, HSV-2, and KSHV in post-ART timepoints with different baseline biomarkers of systemic inflammation suggest that distinct immunological functions are implicated in the control of their viral replication. Show less

After initiating antiretroviral therapy (ART), approximately 25% of people with HIV (PWH) may develop Immune Reconstitution Inflammatory Syndrome (IRIS), which is associated with increased morbidity and mortality. Several reports have demonstrated that low haemoglobin (Hb) levels are a risk factor for IRIS. To what extent the severity of anaemia contributes to the risk of IRIS and/or death is still insufficiently explored. We investigated both the presence and severity of anaemia in PWH in a multinational cohort of ART-na..ve patients. A large panel of plasma biomarkers was measured pre-ART and patients were followed up for 6 months. IRIS or deaths during this period were considered as outcomes. We performed multidimensional analyses, logistic regression, and survival curves to delineate associations. Patients with severe anaemia (SA) presented a distinct systemic inflammatory profile, characterized by higher TNF, IL-6, and IL-27 levels. SA was independently associated with IRIS, with a higher risk of both early IRIS onset and death. Among IRIS patients, those with SA had a higher risk of mycobacterial IRIS. PWH with SA display a more pronounced inflammatory profile, with an elevated risk of developing IRIS earlier and a statistically significant higher risk of death. Intramural Research Program of National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH). Coordena...·o de Aperfei..oamento de Pessoal de N.ível Superior (Finance code: 001) and the Conselho Nacional de Desenvolvimento Cient.ífico e Tecnol..gico (CNPq), Brazil. Show less

Immune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management. Plasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model. We identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort. Systemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART. NCT00286767. Show less

The Neurospora crassa cps-1 gene encodes a polysaccharide synthase with homology to the Cryptococcus neoformans hyaluronic acid synthase Cps1p. Homologs of the cps-1 gene are found in the genomes of many fungi. Loss of CPS-1 results in a cell wall defect that affects all stages of the N. crassa life cycle, including vegetative growth, protoperithecia (female mating structure) development, and conidia (asexual spore) development. The cell wall of cps-1 deletion mutants is sensitive to cell wall perturbation reagents. Our results demonstrate that CPS-1 is required for the incorporation of cell wall proteins into the cell wall and plays a critical role in cell wall biogenesis. We found that the N. crassa cell wall is devoid of hyaluronic acid, and conclude that the polysaccharide produced by the CPS-1 is not hyaluronic acid. Show less