Browsing by Author "Roberts, Lindi."

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Genital tract inflammation during early HIV-infection predicts higher plasma viral load set point in women.
(Oxford University Press., 2011) Roberts, Lindi.; Passmore, Jo-Ann Shelley.; Mlisana, Koleka Patience.; Williamson, Carolyn.; Little, Francesca.; Bebell, Lisa M.; Walzl, Gerhard.; Abrahams, Melissa-Rose.; Woodman, Zenda.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.
Background. The biggest challenge in human immunodeficiency virus type 1 (HIV-1) prevention in Africa is the high HIV-1 burden in young women. In macaques, proinflammatory cytokine production in the genital tract is necessary for target cell recruitment and establishment of simian immunodeficiency virus (SIV) infection following vaginal inoculation. The purpose of this study was to assess if genital inflammation during early HIV-1 infection predisposes women to rapid disease progression. Methods. Inflammatory cytokine concentrations were measured in cervicovaginal lavage (CVL) from 49 women 6, 17, 30, and 55 weeks after HIV-1 infection and from 22 of these women before infection. Associations between genital inflammation and viral load set point and blood CD4 cell counts 12 months after infection were investigated. Results. Elevated genital cytokine concentrations 6 and 17 weeks after HIV-1 infection were associated with higher viral load set points and, to a lesser extent, with CD4 depletion. CVL cytokine concentrations during early infection did not differ relative to preinfection but were elevated in women who had vaginal discharge, detectable HIV-1 RNA in their genital tracts, and lower blood CD4 counts. Conclusion. Genital inflammation during early HIV-1 infection was associated with higher viral load set point and CD4 depletion, which are markers of rapid disease progression. Strategies aimed at reducing genital inflammation during early HIV-1 infection may slow disease progression.
Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression.
(Lippincott Williams & Wilkins., 2010) Roberts, Lindi.; Williamson, Carolyn.; Little, Francesca.; Bebell, Lisa M.; Mlisana, Koleka Patience.; Burgers, Wendy A.; Passmore, Jo-Ann Shelley.; van Loggerenberg, Francois.; Walzl, Gerhard.; Djoba Siawaya, Joel Fleury.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.
Background: Both T-cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown. Objectives: To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression. Design: Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection. Methods: The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set point 12 months postinfection and time taken for CD4 cell counts to fall below 350 cells/ul were determined using multivariate and Cox proportional hazards regression. Results: We found that the concentrations of five plasma cytokines, IL-12p40, IL-12p70, IFN-y, IL-7 and IL-15 in women with acute infection predicted 66% of the variation in viral load set point 12 months postinfection. IL-12p40, IL-12p70 and IFN-y were significantly associated with lower viral load, whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and granulocyte–macrophage colony-stimulating factor during acute infection were associated with maintenance of CD4 cell counts above 350 cells/ul, whereas IL-1a, eotaxin and IL-7 were associated with more rapid CD4 loss. Conclusion: A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women.
Symptomatic vaginal discharge is a poor predictor of sexually transmitted infections and genital tract inflammation in high-risk women in South Africa.
(Oxford University Press., 2011) Mlisana, Koleka Patience.; Naicker, Nivashnee.; Werner, Lise.; Roberts, Lindi.; van Loggerenberg, Francois.; Baxter, Cheryl.; Passmore, Jo-Ann Shelley.; Grobler, Anna Christina.; Sturm, Adriaan Willem.; Williamson, Carolyn.; Ronacher, Katharina.; Walzl, Gerhard.; Abdool Karim, Salim Safurdeen.
Background. Diagnosis and treatment of sexually transmitted infections (STIs) is a public health priority, particularly in regions where the incidence of human immunodeficiency virus (HIV) infection is high. In most developing countries, STIs are managed syndromically. We assessed the adequacy of syndromic diagnosis of STIs, compared with laboratory diagnosis of STIs, and evaluated the association between STI diagnosis and the risk of HIV acquisition in a cohort of high-risk women. Methods. HIV-uninfected high-risk women (n = 242) were followed for 24 months. Symptoms of STIs were recorded, and laboratory diagnosis of common STI pathogens was conducted every 6 months. Forty-two cytokines were measured by Luminex in cervicovaginal lavage specimens at enrollment. Human immunodeficiency virus type 1 (HIV-1) infection was evaluated monthly. Results. Only 12.3% of women (25 of 204) who had a laboratory-diagnosed, discharge-causing STI had clinically evident discharge. Vaginal discharge was thus a poor predictor of laboratory-diagnosed STIs (sensitivity, 12.3%; specificity, 93.8%). Cervicovaginal cytokine concentrations did not differ between women with asymptomatic STIs and those with symptomatic STIs and were elevated in women with asymptomatic STIs, compared with women with no STIs or bacterial vaginosis. Although laboratory-diagnosed STIs were associated with increased risk of HIV infection (hazard ratio, 3.3 [95% confidence interval, 1.5–7.2)], clinical symptoms were not. Conclusions. Syndromic STI diagnosis dependent on vaginal discharge was poorly predictive of laboratory-diagnosed STI. Laboratory-diagnosed STIs were associated with increased susceptibility to HIV acquisition, while vaginal discharge was not.