Infectious Diseases Institute (IDI)

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Browsing Infectious Diseases Institute (IDI) by Subject "AIDS"
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    Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: A prospective cohort study
    (PLoS Medicine, 2010) Boulware, David R. ; Meya, David B. ; Bergemann, Tracy L. ; Wiesner, Darin L. ; Rhein, Joshua ; Musubire, Paul ; Lee, Sarah J. ; Kambugu, Andrew ; Janoff, Edward N. ; Bohjanen, Paul R.
    Background: Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible. Methods and Findings: We prospectively followed 101 ART-naı¨ve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1–5.1, p = 0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p = 0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-a, granulocyte colony-stimulating factor (GCSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p#0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level .32 mg/l (highest quartile). Pre-ART CRP level .32 mg/l alone was associated with future death (OR = 8.3, 95% CI 2.7–25.6, p,0.001). Conclusions: Pre-ART increases in Th17 and Th2 responses (e.g., IL-17, IL-4) and lack of proinflammatory cytokine responses (e.g., TNF-a, G-CSF, GM-CSF, VEGF) predispose individuals to subsequent IRIS, perhaps as biomarkers of immune dysfunction and poor initial clearance of CRAG. Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start ART or use prophylactic interventions.
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    Low prevalence of pneumocystis jirovecii lung colonization in Ugandan HIV-infected patients hospitalized with non-Pneumocystis pneumonia
    (SciVerse ScienceDirect, 2012-02-15) Taylor, Steve, M. ; Meshnick, Steven, R. ; Worodria, William ; Andama, Alfred ; Davis, J. Lucian ; Cattamanchi, Adithya ; Den Boon, Saskia ; Yoo, Samuel D. ; Goodman, Carol D. ; Huang, Laurence
    Pneumocystis jirovecii is an important opportunistic infection in human immunodeficiency virus (HIV)–infected patients. In the developed world, P. jirovecii epidemiology is marked by frequent colonization in immunosuppressed patients, but data on the prevalence of colonization are very limited in sub-Saharan Africa, where the majority of persons living with HIV reside. Our objective was to describe the epidemiology of P. jirovecii colonization among HIV-positive patients in a cross-sectional, hospital-based study of patients admitted with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in bronchoalveolar lavage fluid from 7 (6%) of 124 consecutive patients with non-Pneumocystis pneumonia. Colonization was not associated with patient demographic or clinical information. This prevalence is substantially lower than in published studies in the developed world and suggests that there is a limited reservoir of organisms for clinical infections in this Ugandan population. These findings may partially explain the low incidence of Pneumocystis pneumonia in Uganda and other sub-Saharan African countries.
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    Tuberculosis preventive therapy (TPT) to prevent tuberculosis co-infection among adults with HIV-associated cryptococcal meningitis: A clinician's perspective
    (Elsevier, 2020) Kasibante, John ; Rutakingirwa, Morris K. ; Kagimu, Enock ; Ssebambulidde, Kenneth ; Ellis, Jayne ; Tugume, Lillian ; Mpoza, Edward ; Cresswell, Fiona ; Meya, David B.
    As part of the END TB strategy, the World Health organization (WHO) recommends provision of tuberculosis preventive therapy (TPT) to all people at high risk of developing active TB disease. Patients with HIV-associated cryptococcal meningitis are severely immunocompromised and therefore should be eligible for TPT. In this commentary we discuss the challenges associated with starting tuberculosis preventive therapy in patients with HIV associated cryptococcal meningitis in a clinical setting, we highlight the benefit, existing gaps and research opportunities of tuberculosis preventive therapy in this patient population.