14 research outputs found
The costâeffectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa
Introduction Many HIVâpositive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhancedâprophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the costâeffectiveness of this enhancedâprophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods The REALITY trial enrolled from June 2013 to April 2015. A decisionâanalytic model was developed to estimate the costâeffectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standardâprophylaxis, enhancedâprophylaxis, standardâprophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhancedâprophylaxis (CrAgâpositive) or standardâprophylaxis (CrAgânegative), the second to enhancedâprophylaxis (CrAgâpositive) or enhancedâprophylaxis without fluconazole (CrAgânegative) and the third to standardâprophylaxis with fluconazole (CrAgâpositive) or without fluconazole (CrAgânegative). The model estimated costs, lifeâyears and qualityâadjusted lifeâyears (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhancedâprophylaxis was costâeffective at costâeffectiveness thresholds of US500 per QALY with an incremental costâeffectiveness ratio (ICER) of US113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US2.30. Conclusions The REALITY enhancedâprophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is costâeffective. Efforts should continue to ensure that components are accessed at lowest available prices
Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.
This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children â„5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/”L), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/”L) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/”L), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-LiverpoolâWellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation
Rapid Multiplexed Immunoassay for Detection of Antibodies to Kaposiâs Sarcoma-Associated Herpesvirus
<div><p>Diagnosis of KSHV-infected individuals remains a challenge. KSHV prevalence is high in several populations with high prevalence of HIV, leading to increased risk of development of Kaposiâs sarcoma (KS). While current assays are reliable for detecting antibodies to KSHV, none are routinely utilized to identify individuals with KSHV infection and thus at increased risk for KS due to assay complexity, lack of access to testing, and cost, particularly in resource-limited settings. Here we describe the addition of KSHV proteins LANA and K8.1 to a previously evaluated HIV/co-infection multiplexed fluorescence immunoassay system. This study demonstrates assay performance by measuring antibody reactivity for KSHV and HIV-1 in a collection of clinical specimens from patients with biopsy-proven KS and sourced negative controls. The KSHV assay correctly identified 155 of 164 plasma samples from patients with biopsy-proven KS and 85 of 93 KSHV antibody (Ab)-negative samples for a sensitivity of 95.1% and specificity of 91.4%. Assay performance for HIV-1 detection was also assessed with 100% agreement with independently verified HIV-1 Ab-positive and Ab-negative samples. These results demonstrate good sensitivity and specificity for detection of antibody to KSHV antigens, and demonstrate the potential for multiplexed co-infection testing in resource-limited settings to identify those at increased risk for HIV-1-related complications.</p></div
ROC curve for MBio assay, including individual antigens, LANA and K8.1 and maximum S/CO.
<p>ROC curve for MBio assay, including individual antigens, LANA and K8.1 and maximum S/CO.</p
Signal / Cutoff values for the KSHV antigens LANA and K8.1 in the MBio Array cartridge.
<p>âPOSâ indicates the Kaposiâs Sarcoma biopsy-positive samples. âNEGâ indicates negative control sera as determined by KSHV ELISA. The box and whisker plots show the median, 10<sup>th</sup>, 25<sup>th</sup>, 75<sup>th</sup> and 90<sup>th</sup> percentiles. The circles show location of the 5<sup>th</sup> and 95<sup>th</sup> percentiles.</p