Suchergebnisse

BackgroundCryptococcal meningitis is a leading cause of death among HIV‐infected individuals in sub‐Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre‐emptive treatment. In this study, we describe the impact of screening HIV‐positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital.MethodsAll adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV‐positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in‐hospital mortality were recorded.ResultsOf 333 HIV‐infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in‐hospital deaths.ConclusionsDespite screening of all HIV‐positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high‐dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in‐hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre‐emptive treatment for high‐risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed.

BackgroundDetection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV‐positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre‐emptively. Recently developed point‐of‐care cryptococcal antigen tests may be useful for screening, particularly in resource‐limiting settings, but few studies have assessed their utility.MethodologyThe objectives of this study were to determine the prevalence and factors associated with cryptococcal antigenemia in HIV‐positive patients with CD4+ T‐cell counts ≤200 cells/µL who were initiating ART, and also to evaluate the utility of the point‐of‐care urine lateral flow assay (LFA) cryptococcal antigen test using two different diluents, compared to gold standard serum antigen testing, as a screening tool. Urine and serum of outpatients initiating antiretroviral therapy at two hospitals in Mwanza were tested for cryptococcal antigen, and demographic and clinical characteristics were obtained using structured questionnaires and patients' files. Patients with asymptomatic cryptococcal antigenemia received oral fluconazole in accordance with World Health Organization recommendations.ResultsAmong 140 patients screened, 10 (7.1%) had asymptomatic cryptococcal antigenemia with a positive serum cryptococcal antigen. Four of these ten patients had CD4 counts between 100 and 200 cells/µL. The prevalence of cryptococcal antigen detected in urine using a standard (older) and a test (newer) diluent were 44 (31.4%) and 19 (13.6%), with Kappa coefficients compared to serum of 0.28 and 0.51 (p<0.001 for both). Compared to the new LFA diluent for urine cryptococcal antigen, the standard diluent had higher sensitivity (100% versus 80%) but lower specificity (74% versus 92%) using serum cryptococcal antigen as a gold standard.ConclusionsOur findings suggest that HIV‐positive outpatients with CD4 counts <200 cells/µL, rather than 100, should be screened for asymptomatic cryptococcal antigenemia given its association with mortality if untreated. Agreement of the urine LFA with the serum LFA was not sufficient to recommend routine screening with urine LFA.

BackgroundSince HIV‐1 RNA (viral load) testing is not routinely available in Haiti, HIV‐infected patients receiving antiretroviral therapy (ART) are monitored using the World Health Organization (WHO) clinical and/or immunologic criteria. Data on survival and treatment outcomes for HIV‐1 infected patients who meet criteria for ART failure are limited. We conducted a retrospective study to compare survival rates for patients who experienced failure on first‐line ART by clinical and/or immunologic criteria and switched to second‐line ART vs. those who failed but did not switch.MethodsPatients receiving first‐line ART at the GHESKIO Center in Port‐au‐Prince, Haiti, who met WHO clinical and immunologic criteria for failure were identified. Survival and treatment outcomes were compared in patients who switched their ART regimen and those who did not. Cox regression analysis was used to determine predictors of mortality after failure of first‐line ART.ResultsOf 3126 patients who initiated ART at the GHESKIO Center between 1 March 2003 and 31 July 2008, 482 (15%) met WHO immunologic and/or clinical criteria for failure. Among those, 195 (41%) switched to second‐line ART and 287 (59%) did not. According to Kaplan–Meier survival analysis, the probability of survival to 12 months after failure of first‐line ART was 93% for patients who switched to second‐line ART after failure and 88% for patients who did not switch. Predictors of mortality after failure of first‐line ART were weight in the lowest quartile for sex, CD4 T cell count ≤ 100, adherence < 90% at the time of failure and not switching to second‐line ART.ConclusionsPatients who failed first‐line ART based on clinical and/or immunologic criteria and did not switch to second‐line therapy faced a higher mortality than those who switched after failure. To decrease mortality, interventions to identify patients in whom ART may be failing earlier are needed urgently. In addition, there is a major need to optimize second‐line antiretroviral regimens for improved potency, lower toxicity and greater convenience for patients.

IntroductionAdolescents account for over 40% of new HIV infections in Haiti. This analysis compares outcomes among HIV‐positive adolescents before and after implementation of an adolescent HIV clinic in Port‐au‐Prince, Haiti.MethodsWe conducted a cohort study using programmatic data among HIV‐positive adolescents aged 13 to 19. Data from 41,218 adolescents who were HIV tested from January 2003 to December 2012 were included. Outcomes across the HIV care cascade were assessed before and after implementation of an adolescent clinic (2009), including HIV testing, enrolment in care, assessment for antiretroviral therapy (ART) eligibility, ART initiation and 12‐month retention. Pre‐ART outcomes were assessed 12 months after HIV testing. Factors associated with pre‐ART and ART attrition were identified through multivariable competing risk and Cox proportional hazards regression modelling.ResultsCumulatively, 1672 (4.1%) adolescents tested HIV positive (80% female, median age 16 years). Retention by cascade step comparing pre‐ and post‐clinic included the following: 86% versus 87% of patients enrolled in care, 61% versus 79% were assessed for ART eligibility, 85% versus 92% initiated ART and 68% versus 66% were retained 12 months after ART initiation. Pre‐ART attrition decreased from 61% pre‐clinic to 50% post‐clinic (p<0.001). Pre‐ART attrition was associated with being female (sub‐distributional hazard ratio (sHR): 1.59; CI: 1.31–1.93), syphilis diagnosis (sHR: 1.47; CI: 1.16–1.85) and slum residence (sHR: 0.84; CI: 0.72–0.97). ART attrition was associated with syphilis diagnosis (hazard ratio (HR): 2.23; CI: 1.35–3.68) and CD4 <50 cells/µL (HR: 1.88; CI: 1.15–3.06).ConclusionsImplementation of a youth‐friendly adolescent clinic improved retention in HIV care among adolescents, particularly in the assessment of ART eligibility and ART initiation. Additional interventions are needed to improve retention among pre‐ART patients and support long‐term retention among ART patients.