Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda

University of California, San Francisco, San Francisco, California, United States
Tropical Medicine & International Health (Impact Factor: 2.3). 08/2007; 12(8):929-35. DOI: 10.1111/j.1365-3156.2007.01874.x
Source: PubMed

ABSTRACT To evaluate the association between a positive serum cryptococcal antigen (CRAG) test at baseline and mortality during the first 12 weeks on antiretroviral therapy (ART). Cryptococcal meningitis is a leading cause of HIV-related mortality in Africa, but current guidelines do not advocate CRAG testing as a screening tool.
Between May 2003 and December 2004, we enrolled HIV-1 infected individuals into a study of ART monitoring in rural Uganda. CRAG testing was conducted retrospectively on stored pre-ART serum samples of participants whose baseline CD4 cell count was <100 cells/mul and who were without symptoms suggestive of disseminated cryptococcal disease at enrolment.
Of 377 participants, 5.8% had serum CRAG titre >/=1:2. Of these, 23% died during follow-up. Controlling for CD4 cell count, HIV-1 viral load, anaemia, active tuberculosis and body mass index, relative risk of death during follow-up among those with asymptomatic cryptococcal antigenemia at baseline was 6.6 [95% confidence interval (CI) 1.86-23.61, P = 0.0036]. The population attributable risk for mortality associated with a positive CRAG at baseline was 18% (CI 2-33%), similar to that associated with active tuberculosis (19%, CI 1-36%).
Asymptomatic cryptococcal antigenemia independently predicts death during the first 12 weeks of ART among individuals with advanced HIV disease in rural Uganda. Routine screening and provision of azole antifungal therapy prior to or simultaneous with the start of ART should be evaluated for the potential to prevent mortality in this population.

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    • "However, the magnitude of the survival difference is substantially below that reported in prior research of individuals with untreated asymptomatic cryptococcal infection. A study from Uganda noted a relative risk of death of 6.6 [95%CI: 1.86, 23.61] (Liechty et al. 2007) and a study from South Africa noted a hazard ratio of 4.75 [95% CI: 2.6, 8.8] and an adjusted hazard ratio of 3.2 [95% CI: 1.5. 6.6] for individuals with asymptomatic cryptococcal infection (Jarvis et al. 2009). "
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    ABSTRACT: OBJECTIVES: To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. METHODS: Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4 ≤ 100 cells/μl were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre ≥ 1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4 ≤ 100 cells/μl in the intervention and historical control groups. RESULTS: The median age was 34 years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/μl [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group, 66% (514/782) were tested for sCrAg; of whom, 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [hazard ratio (HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg-positive individuals had significantly lower survival rates than sCrAg-negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. CONCLUSIONS: A screening and treatment intervention to identify sCrAg-positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts ≤ 100 cells/μl compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole.
    Tropical Medicine & International Health 02/2013; 18(4). DOI:10.1111/tmi.12067 · 2.30 Impact Factor
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    ABSTRACT: The success of antiretroviral therapy (ART) programs in the developing world is limited by the lack of adequate diagnostic tests to screen for life-threatening opportunistic infections such as tuberculosis (TB) and cryptococcal disease. Furthermore, there is an increasing need for implementation research in measuring the effectiveness of currently available rapid diagnostic tests. The recently developed lateral flow assays for both cryptococcal disease and TB have the potential to improve care and greatly reduce the time to initiation of ART among individuals who need it the most. However, we caution that the data on feasibility and effectiveness of these assays are limited and such research agendas must be prioritized.
    09/2013; 12(5):301-5. DOI:10.1177/2325957413500472
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    ABSTRACT: Cryptococcal meningitis is one of the most important fungal infections in the developing world, where deaths related to this disease are numerous. In resource-limited settings, mortality is high in large part because of difficulties in the diagnosis and management of this infection. This paper outlines many of the realities in many resource-limited settings, and describes priorities for public health action and research.
    Current Fungal Infection Reports 03/2012; 6(1). DOI:10.1007/s12281-011-0082-6
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