Browsing by Author "Sivro, Aida."
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Item Bugs, drugs, and HIV : the role of the vaginal microbiome in HIV risk and antiretroviral efficacy for HIV prevention.(BioMed Central., 2017) Liebenberg, Lenine Julie.; Archary, Derseree.; Sivro, Aida.; Kwon, Douglas S.Abstract available in pdf.Item Ex vivo HIV entry into blood CD4+ T cells does not predict heterosexual HIV acquisition in women.(Public Library of Science., 2018) Joag, Vineet.; Sivro, Aida.; Yende-Zuma, Fortunate Nonhlanhla.; Imam, Hajra.; Samsunder, Natasha.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; McKinnon, Lyle R.; Kaul, Rupert.Abstract available in pdf.Item Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women.(Nature Publishing Group., 2018) McKinnon, Lyle R.; Liebenberg, Lenine Julie.; Yende-Zuma, Fortunate Nonhlanhla.; Archary, Derseree.; Ngcapu, Sinaye.; Sivro, Aida.; Nagelkerke, Nico.; Garcia Lerma, Gerardo.; Kashuba, Angela D. M.; Masson, Lindi.; Mansoor, Leila Essop.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Passmore, Jo-Ann Shelley.Abstract available in pdf.Item In vitro effects of intravaginal insertion products (IVIPs) on biomarkers of inflammation and immune cellular activation in the era of HIV.(2019) Hlophe, Rejoice Zanele.; Gumbi, Pamela Phumelele.; Sivro, Aida.; Ngcapu, Sinaye.The use of vaginal products is associated with increased HIV acquisition risk, but the mechanism is not fully understood. Vaginal practices entail the use of a wide variety of products which can alter the vaginal environment to achieve a desired state. Strong motivations for vaginal practices include women’s desire to maintain stable relationships, manage health, hygiene and sexuality. This adjustment of the vaginal microenvironment may increase HIV acquisition risk. High levels of inflammation and immune activation in the female genital tract are associated with a threefold increase in HIV acquisition risk. We hypothesized that intravaginal insertion products (IVIPs) may be linked to high levels of inflammation and immune activation in the female genital tract which may subsequently lead to an increased risk of HIV acquisition Objective The pH of the IVIPs (Kuber, Snuff, Alum, Savlon and Rose water) was measured and the cytotoxicity of the IVIPs was evaluated by determining their effect on cell viability at different dilutions (Neat/stock, 1/5, 1/10, 1/100 and 1/1000). The mechanisms by which potassium aluminium sulfate (“Alum”) and smokeless tobacco (“snuff”) impact cellular activation and inflammation were investigated using peripheral blood mononuclear cells (PBMCs) in vitro. Methods The pH of alum, snuff, kuber, savlon and rose water was measured at different dilutions (Neat/Stock, 1/5, 1/10, 1/100 and 1/1000). The effect of the IVIPs on cell viability was determined by exposing PBMCs to the different dilutions of IVIPs mentioned above. PBMCs from 26 HIV-negative healthy donors were unstimulated (negative control) or stimulated for 3 hours at 37°C with 1/1000 dilutions of 450 mg/ml of alum or snuff and 10μg/ml of PHA (positive control). The PBMC supernatants were collected following PBMC stimulation, and eleven cytokines were measured from 12 of the 26 PBMC supernatants. Pro-inflammatory (IL-1β, TNF-α, IL-6), chemokines (IL-8, IP-10, MIP-1α, MIP-1β, MCP-1), hematopoietic (IL-7, GM-CSF) and regulatory (IL-10) cytokines were measured using Bio-Plex multiplex assay. The activation status of T lymphocytes was determined by evaluating CD38+, HLA-DR+, dual expression of CD38+HLA-DR+ and chemokine receptor CCR5+ expression from CD4+ and CD8+ T cells using flow cytometry assay. Results Alum stock solution was acidic with a pH of 2.62 whereas the snuff stock solution was basic with a pH of 9.11. Alum and savlon were found to have high cytotoxicity. Snuff exposed cell resulted in a significantly increased CCR5 chemokine expression in CD4+ T cells when compared to the unexposed cells (p=0.0483) and also when compared to alum exposed cells (p=0.0446). However, snuff exposure did not significantly increase any of the activation markers in CD8+ T cells and it did not change the inflammatory cytokine profile. In CD8+ T lymphocytes the CD38+ biomarker was significantly more expressed in unexposed cells compared to the alum exposed cells (p=0.0185). Alum exposed cells significantly increased expression of HLADR+ (P=0.0348) and also the dual expression of CD38+HLA-DR+in CD8+ T cells (p=0.0208) when compared to the unexposed cells and was also associated with significantly high levels of cytokines IP-10 (p=0.039), MCP-1 (P=0.0024), MIP-1α (p=0.0005), IL-6 (P=0.0005), TNF-α (P=0.0020), IL-7 (P=0.0005) and GM-SCF (P=0.0005) when compared to the unexposed cells. Conclusion This study is the first of its kind to identify a possible link between intravaginal insertion products and inflammation. Alum, in particular, was more inflammatory compared to snuff. These findings may help explain the previous observations of an increased HIV acquisition risk in IVIP users. Future research can extend the current pilot study on an invitro human vaginal epithelial cell model. Knowledge from this work and future studies is crucial in developing new female-initiated interventions for preventing HIV acquisition.Item Mucosal HIV shedding during ART.(Oxford University Press., 2017) Sivro, Aida.; McKinnon, Lyle R.Abstract available in pdf.Item Systemic lymphocyte trafficking markers in TB and TB/HIV co-infections.(2019) Pillay, Kimesha.; Sivro, Aida.; Naidoo, Kogieleum.Background. Several studies demonstrate that immune inflammation and trafficking of immune cells to affected tissues plays a major role in the pathogenesis of tuberculosis (TB) and human immunodeficiency virus (HIV) infections; however, characterization of soluble markers of lymphocyte trafficking and inflammation in the context of TB and TB/HIV co-infection remains to be elucidated. Here we sought to evaluate the role of specific lymphocyte trafficking and inflammatory markers as predictors of TB disease. Methods. The presented study was performed on stored plasma samples from TB Recurrence upon Treatment with HAART (TRuTH) and Improving Recurrence Success (IMPRESS) cohorts. TB recurrent cases (n = 37) were matched to controls (n = 103) on study arm in the original trial and antiretroviral therapy (ART) start date. A subset of cases was followed longitudinally at: preTB, active TB and postTB/cure timepoints. In IMPRESS a subset of HIV infected (n = 41) and HIV uninfected (n = 37) individuals were sampled at active TB disease and post TB/cure. Plasma concentrations of soluble mucosal addressin cell adhesion molecule (sMAdCAM), soluble intracellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM), lipopolysaccharide binding protein (LBP) and transforming growth factor – beta (TGF-β) were measured using enzyme-linked immunosorbent assays (ELISAs) and Multiplex assays. Results. Two analytes were associated with increased rate of TB recurrence in the univariate model: square root transformed (sqrt) sICAM (odds ratio [OR] 1.047. 95% confidence interval [CI] 1.014 – 1.081, p = 0.005) and sqrtLBP (OR 3.283, 95% CI 1.018 – 10.588, p = 0.047) and the multivariable model. Longitudinal analysis showed reduced levels of LBP, sMAdCAM and sVCAM and an increase in levels of TGF- β3 during the entire follow-up. In IMPRESS data, trends of increased plasma LBP from active TB to post TB/cure in HIV infected individuals and trends of reduced plasma LBP in HIV uninfected individuals post treatment were observed. Conclusion. The TRuTH data demonstrates that plasma levels of sICAM and LBP can act as predictors of TB recurrence in HIV infected individuals receiving ART treatment. A decrease of plasma LBP levels from active TB to treatment completion in HIV uninfected individuals likely suggests that active TB and associated inflammatory changes are associated with gut inflammation and dysbiosis.