Browsing by Author "Sivro, Aida."

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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.
Evaluation of laboratory tests for COVID-19 in South Africa.
(2023) Samsunder, Natasha.; Kharsany, Ayesha Bibi Mahomed.; Sivro, Aida.
Abstract available in PDF.
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.
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.
Immune biomarkers of pulmonary tuberculosis treatment response and disease severity among HIV-infected and uninfected individuals from Kwazulu-Natal, South Africa.
(2023) Rambaran, Santhuri.; Sivro, Aida.; Naidoo, Kogieleum.
Background: Tuberculosis is one of the major causes of morbidity and mortality worldwide. The COVID -19 pandemic has had a devastating impact on TB, contributing to increased incidence of both TB and drug-resistant TB. Identification of host immune biomarkers of TB risk, treatment outcome and disease severity are key to the development of more efficient diagnostics and treatment modalities. There is an urgent need for accurate and easily detectable non-sputum-based biomarkers that can correlate with the activity or burden of Mycobacterium tuberculosis. Here, we characterised soluble and cellular phenotypes during active TB and TB/HIV co-infection and assessed their associations with time to negative culture conversion and disease severity. Methods: The study was performed utilizing stored plasma and peripheral blood mononuclear cells from the Improving Retreatment Success (IMPRESS) trial. Multiplex immunoassays and ELISAs were used to evaluate 24 cytokine and chemokine expression during active TB (n=132). Flow cytometry was used to evaluate phenotypic profiles of monocytes, dendritic cells (n=90) and CD4+ T cells (n=75). A Cox proportional hazards and logistic regression models were used to assess the associations between the measured cytokines and chemokines, phenotypic profiles of monocytes, dendritic cells and CD4+ T cells and time to negative culture conversion and lung cavitation in individuals with TB and TB/HIV co-infection. Results: We identified soluble inflammatory signatures of treatment response and disease severity. IP-10 expression during active TB was associated with increased odds of sputum culture conversion by 8-weeks in the total cohort and among the HIV-infected individuals. Increased MCP-3 expression was associated with a shorter time to culture conversion in the total cohort. While among the HIV-infected individuals, higher expression of IL-1RA, IP-10 and IL-1α associated with a shorter time to culture conversion. Higher expression of IL-6 was significantly associated with shorter time to culture conversion and increased risk of lung cavitation in the overall cohort and among TB/HIV co-infected individuals. Additionally, higher IL-1RA expression was associated with the presence of lung cavitation in the total cohort and in HIV-infected individuals. We observed distinct monocyte and dendritic cell profiles in TB/HIV co-infection. Individuals with TB/HIV co-infection had a significantly higher percentage of total monocytes and dendritic cells compared to healthy controls. Increase in CCR2, CD11b and CD40 was associated with active TB while decrease in CX3CR1 and increase in CD163 was associated with HIV infection. Expression of CX3CR1 on non-classical monocytes was associated with longer time to culture conversion while expression of CD86 on intermediate monocytes was associated with presence of lung cavitation. With respect to CD4+ T cells HIV positive individuals with active TB had significantly lower percentage of CD4+ T cells and significantly higher proportion of activated CD4+ T cells compared to TB and healthy control groups. Percentage of CD4+ T cells was significantly associated with increased risk, while the percentage of activated CD4+ T cells was associated with decreased risk of lung cavitation. Integrin α4β7 expressing CD4+ T cells were increased in TB/HIV compared to TB group and was associated with longer time to TB culture conversion in co-infected individuals. Conclusion: The data from this study provides valuable insight into the role that plasma immune biomarkers, monocytes, dendritic and CD4+ T cells play in TB treatment response and disease severity in active TB and TB/HIV co-infection.
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.
Inflammation and cellular immune phenotypes in TB/HIV co-infection.
(2023) Maseko, Thando Glory.; Sivro, Aida.; Archary, Derseree.
Abstract available in PDF.
Mucosal HIV shedding during ART.
(Oxford University Press., 2017) Sivro, Aida.; McKinnon, Lyle R.
Abstract available in pdf.
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.
Type I, II, and III interferon responses in the female genital tract.
(2024) Ngubane, Slindile Brilliant Lyzeth.; Sivro, Aida.
Abstract available in PDF.