Browsing by Author "Liebenberg, Lenine Julie."

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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.
Distinct genital tract HIV-specific antibody profiles associated with Tenofovir gel.
(Nature., 2016) Archary, Derseree.; Seaton, Kelly E.; Passmore, Jo-Ann Shelley.; Werner, Lise.; Deal, Aaron W.; Dunphy, Laura J.; Arnold, Kelly B.; Yates, Nicole L.; Lauffenburger, Douglas A.; Bergin, Philip.; Liebenberg, Lenine Julie.; Samsunder, Natasha.; Mureithi, Marianne W.; Altfeld, Marcus.; Garrett, Nigel Joel.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Morris, Lynn.; Tomaras, Georgia D.
Abstract available in PDF file.
Genital inflammation and the risk of HIV acquisition in women.
(Oxford University Press., 2015) Masson, Lindi.; Passmore, Jo-Ann Shelley.; Liebenberg, Lenine Julie.; Werner, Lise.; Baxter, Cheryl.; Arnold, Kelly B.; Williamson, Carolyn.; Little, Francesca.; Mansoor, Leila Essop.; Naranbhai, Vivek.; Lauffenburger, Douglas A.; Ronacher, Katharina.; Walzl, Gerhard.; Garrett, Nigel Joel.; Williams, Brent L.; Couto-Rodriguez, Mara.; Hornig, Mady.; Lipkin, Walter Ian.; Grobler, Anna Christina.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.
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.
Genital tract immune activation, inflammation and sexually transmitted infections in CAPRISA 008 trial participants.
(2016) Mhlungu, Sanele Nobleman.; Liebenberg, Lenine Julie.; Ngcapu, Sinaye.
Abstract available in PDF file.
Genital—systemic chemokine gradients and the risk of HIV acquisition in women.
(Wolters Kluwer Health., 2017) Liebenberg, Lenine Julie.; Masson, Lindi.; Arnold, Kelly B.; McKinnon, Lyle R.; Werner, Lise.; Proctor, Elizabeth.; Archary, Derseree.; Mansoor, Leila Essop.; Lauffenburger, Douglas A.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Passmore, Jo-Ann Shelley.
Abstract available in pdf.
The impact of point-of-care testing and treatment of sexually transmitted infections and bacterial V aginosis on the genital epithelial barrier integrity.
(2022) Ndlela, Nonsikelelo.; Liebenberg, Lenine Julie.
In sub-Saharan Africa, women and young girls suffer the highest burden of HIV infections. Inflammation at the genital tract is a factor responsible for the increased susceptibility to HIV risk in women, presumably through related epithelial barrier damage and target cell recruitment. Considering the direct contribution of sexually transmitted infections (STIs) and bacterial vaginosis (BV) to this inflammation, their effective treatment could potentially reduce HIV risk in this vulnerable population. It has recently been shown in South African women that a point-of-care (POC) STI/BV detection model, immediate treatment, and expedited partner therapy (EPT) resolved STIs and reduced concentrations of genital proinflammatory cytokines. This study investigated an additional impact of the model on the genital epithelial barrier. Methods POC STI/BV screening was conducted on HIV-negative women (n=238) enrolled in the CAPRISA 083 trial between May 2016 and June 2017. Chlamydia trachomatis and Neisseria gonorrhoeae infections were detected by Xpert CT/NG test, while the OSOM Rapid test detected Trichomonas vaginalis. Women were further tested for Mycoplasma genitalium and BV using PCR and microscopy, respectively. Multiplex ELISA was used to quantify 48 cytokines and five matrix metalloproteinase (MMP) biomarkers of epithelial barrier integrity from menstrual cup (MC) specimens (MMP-1, MMP-2, MMP-7, MMP-9, MMP-10). Mann- Whitney U tests were used to assess the relationship between MMPs and STI/BV at baseline, with ANOVA and multivariable linear mixed models used to determine the impact of treatment on MMP concentrations. Results At baseline, women diagnosed with STI/BV (170/238) had higher concentrations of all MMPs compared to women with neither STI/BV (68/238; p>0.05). Several proinflammatory and chemotactic cytokine concentrations correlated significantly with that of MMPs at baseline. By 12 weeks post-treatment, 31/35 (88.57%) women resolved their baseline STIs, while only 14/57 (24.56%) resolved their baseline BV status. Most participants received concurrent treatment for STIs and BV (n=60), with few receiving treatments for STI (n=3) or BV alone15 (n=25). Significant reductions in MMP-1 concentrations were observed after 6 weeks in women treated for STI and BV (2.763 pg/ml; p= 0.0066) or STIs regardless of BV status (2.760 pg/ml; p= 0.0048). No changes in MMP concentrations were observed in women treated for BV. Conclusion POC STI/BV treatment was associated with a reduction in MMP-1 concentrations. This implies that although POC STI/BV treatment may treat STIs and reduce inflammation, the integrity of the genital epithelial barrier may not be fully restored, and women remain susceptible to genital infections, including HIV, as a result. Additional strategies may be needed to repair the genital epithelium after treatment.
The impact of semen exposure on the immune and microbial environments of the female genital tract.
(2021) Jewanraj, Janine.; Liebenberg, Lenine Julie.; Ngcapu, Sinaye.
Background: Semen is an immunomodulatory fluid that induces mucosal changes at the female genital tract (FGT) for sperm survival and conception. Semen-induced alterations necessary for reproduction may also modulate the inflammatory environment related to HIV risk in women. This thesis investigated the impact of semen exposure on biomarkers of female genital inflammation (GI) and the persistence of these associations over time. Methods: Stored genital specimens were assessed from HIV-negative women participating in the CAPRISA 008 trial. Cervicovaginal lavage (CVL) samples were screened for Y-chromosome DNA (YcDNA) by real-time PCR as a biomarker of semen exposure within 15 days of genital sampling. Prostate-specific antigen (PSA) detection by ELISA stratified CVLs into semen exposure within 48 hours (PSA+YcDNA+) and between 3-15 days (PSA-YcDNA+). Vaginal cytokine concentrations, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were assessed in CVLs using multiplexed ELISA. Endocervical T-cell frequencies were measured in cytobrushes by flow-cytometry. Vaginal microbes and sexually transmitted infections (STIs) were detected in vulvovaginal swabs by PCR. Results: Self-reported condom use as a measure of semen exposure was not associated with changes in the FGT microenvironments. Conversely, YcDNA detection predicted significant increases in several cytokines, barrier-related proteins, and Prevotella bivia detection (p=0.001). Since YcDNA detection alone was not associated with the immune environment linked to HIV risk, this thesis further investigated the contribution of more recent sex to female GI. PSA detection (semen exposure within 48 hours) was associated with higher YcDNA concentrations (p<0.0001), suggesting a relationship between the timing of semen exposure and vaginal YcDNA concentrations after condomless sex. In support of this, both PSA detection and higher YcDNA concentrations predicted significant increases in several cytokines, barrier-related proteins (MMP-2, TIMP-1, TIMP-4), and higher frequencies of activated CD4+HLA-DR+ T-cells (p=0.032) and CD4+CCR5+HLA-DR+ HIV targets (p=0.046). PSA detection was also associated with increased detection of several bacterial vaginosis (BV)-associated microbes and reduced Lactobacillus jensenii detection. Conclusion: Recent semen exposure contributes to the inflammatory environment associated with HIV risk in women. These studies highlight the need for clinical and immunological studies of STIs and their biomedical interventions to consider semen’s contribution to the immune and microbial microenvironments of the FGT.
Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells.
(Nature., 2016) Arnold, Kelly B.; Burgener, Adam D.; Birse, Kenzie D. M.; Romas, Laura.; Dunphy, Laura J.; Shahabi, Kamnoosh.; Abou, Max.; Westmacott, Garrett R.; McCorrister, Stuart J.; Kwatampora, Jessie.; Nyanga, Billy.; Kimani, Joshua.; Masson, Lindi.; Liebenberg, Lenine Julie.; Abdool Karim, Salim Safurdeen.; Passmore, Jo-Ann Shelley.; Lauffenburger, Douglas A.; Kaul, Rupert.; McKinnon, Lyle R.
Abstract available in pdf.
Investigation of multiple concurrent Human papillomavirus infections, oncogenicity, and STI co-infection as risk factors for Human immunodeficiency virus infection.
(2017) Jewanraj, Janine.; Liebenberg, Lenine Julie.; Archary, Derseree.
Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STIs) globally and a necessary factor for cervical cancer development. While HPV infection has been associated with increased Human immunodeficiency virus (HIV) risk, the underlying mechanisms remain unclear. Since STIs upregulate cytokine production and immune cell recruitment, and reduce epithelial barrier integrity, this study investigated whether the immune responses associated with HPV infection contribute to a genital immune environment conducive to an increased risk of HIV infection. Methods: This study included a baseline assessment of 167 HIV negative women participating in the CAPRISA 008 trial. The Roche Linear Array was used to detect the presence of 37 HPV genotypes in cervicovaginal lavage (CVL) pellets. The concentrations of 48 cytokines and 9 matrix metalloproteinases (MMPs) were assessed in matching CVL supernatants by multiplex ELISA. The frequencies of activated or proliferating T cells, NK cells, and of HIV target cells were assessed on cervical cytobrush-derived specimens by flow cytometry. Multiplex PCR was conducted to determine infection with common discharge-associated STIs. Results: The study demonstrated a 50.8% HPV prevalence. HPV infection was associated with younger age, older male partners, not living with a regular partner, and higher parity. HPV infection was also associated with greater levels of IL-5, IL-6 and G-CSF, an association otherwise masked by the inflammatory nature of other STI. Concomitant HPV/STI infection resulted in reduced concentrations of IL-6 and IL-1RA relative to HPV-STI+ women. In multivariate analyses controlling for other STI and nugent score, HPV-infected women had increased concentrations of SDF-1α (β = 0.148 pg/ml). Women with HR-HPV had higher concentrations of MCP-1 (β = 0.127 pg/ml) and IL-13 (β = 0.117 pg/ml), and greater frequencies of lymphocytes (β = 1.987 pg/ml) relative to those infected with LR-HPV. Having multiple HPV infections was associated with reduced concentrations of IL-5 (β = -0.170 pg/ml). Conclusion: While discharge-related STIs are inflammatory, a more subtle immune profile was associated with HPV infection that did not overtly relate to an increased potential for HIV risk. However, this study demonstrated an association between HR-HPV and biomarkers of inflammation, suggesting the need for longitudinal investigation to confirm a biological mechanism for the relationship between persistent HR-HPV infection and HIV acquisition.
Randomized cross-sectional study to compare HIV-1 specific antibody and cytokine concentrations in female genital secretions obtained by menstrual cup and cervicovaginal lavage.
(Public Library of Science., 2015) Archary, Derseree.; Liebenberg, Lenine Julie.; Werner, Lise.; Tulsi, Sahil.; Majola, Nelisile.; Naicker, Nivashnee.; Dlamini, Sarah Alexandra.; Hope, Thomas J.; Samsunder, Natasha.; Abdool Karim, Salim Safurdeen.; Morris, Lynn.; Passmore, Jo-Ann Shelley.; Garrett, Nigel Joel.
Abstract available in pdf.