The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction Many HIV‐positive 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 enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost‐effectiveness of this enhanced‐prophylaxis 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 decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced‐prophylaxis components. Enhanced‐prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced‐prophylaxis still conveyed health gains in CrAg‐negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost‐effective unless the price of CrAg testing fell below US$2.30. Conclusions The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. 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 ≥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/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) 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/µL), 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-Liverpool–Wellcome 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

Effects of Emerging Chemical Contaminants on Water Resources and Environmental Health

A major issue that has remained prevalent in today’s modern world has been the presence of chemicals within water sources that the public uses for drinking. The associated health risks that accompany these contaminants are unknown but have sparked serious concern and emotive arguments among the global community. Empirical research is a necessity to further understand these contaminants and the effects they have on the environment.Effects of Emerging Chemical Contaminants on Water Resources and Environmental Health is a pivotal reference source that provides vital research on current issues regarding the occurrence, toxicology, and abatement of emerging contaminants in water sources. While highlighting topics such as remediation techniques, pollution minimization, and technological developments, this publication explores sample preparation and detection of these chemical contaminants as well as policy and legislative issues related to public health. This book is ideally designed for environmental engineers, bИспользуемые программы Adobe AcrobatОсновной проблемой, которая остается распространенной в современном мире, является наличие химических веществ в источниках воды, которые население использует для питья. Связанные с этими загрязнителями риски для здоровья неизвестны, но вызвали серьезную озабоченность и эмоциональные споры среди мирового сообщества. Эмпирические исследования необходимы для дальнейшего понимания этих загрязняющих веществ и воздействия, которое они оказывают на окружающую среду. Воздействие появляющихся химических загрязнителей на водные ресурсы и здоровье окружающей среды является основным справочным источником, который предоставляет жизненно важные исследования по текущим вопросам, касающимся возникновения, токсикологии и борьбы с появлением загрязняющих веществ в водных источниках. Освещая такие темы, как методы восстановления, минимизация загрязнения и технологические разработки, эта публикация исследует подготовку проб и обнаружение этих химических загрязнителей, а также политические и законодательные вопросы, связанные с

Effect of packaging materials on weight loss and nutrient quality changes of rechanded sweet potatoes (Ipomoea batatas Poir) during short-term storage

The effects of packaging materials on weight loss and nutrient quality changes of recharged submerged in clean tap water) sweet potatoes (Ipomoea batatas Poir) roots during storage were determined. Sweet potatoes from two genotypes, ‘KEMB 10\' and ‘Yanshu\' were recharged for 14 hours and packaged in perforated polyethylene bags (0.02 mm), Kraft paper bags (0.025 mm) and nylon gunnysacks, with roots placed on open plate as control. The packages were then stored at prevailing ambient conditions (23 &#177 2 oC, 77.5 &#177 5.5 % relative humidity (RH)) for 21 days. During storage the sweet potatoes\' change in weight was determined every 3 days. Change in reduced ascorbic acid, &#223-carotene, total sugars and total soluble solids contents were determined every 7 days. There was a significant (p &#8804 0.05) weight loss as well as reduced ascorbic acid loss, but total sugars and &#223-carotene contents increased during storage. Although total sugars showed an apparent gradual increase in all packages and genotypes during storage, the increase was not significant (p &#8804 0.05). Perforated polyethylene bags significantly (p &#8804 0.05) prevented weight loss (up to 1.8 %) as well as allowed for the most retention in reduced ascorbic acid (13.45 g/100 g fresh weight), and increase in &#223-carotene (4.9 mg/100 g fresh weight) and total sugar (6.4 g/100 g dry weight) contents than Kraft paper bags and nylon gunnysacks. Roots packaged in Kraft paper bags were not different in weight and nutrient quality changes from those packaged in nylon gunnysacks. The control sweet potatoes always showed the highest losses in weight (up to 27.8 %) and nutrient quality. Packaging materials did not affect total soluble solids content during storage. The results show that packaging in perforated polyethylene bags can improve shelf life of recharged sweet potatoes by 14 days.Keywords: Ipomoea batatas; packaging; weight lossJAGST Vol 6(1) 2004: 29-4

Effects of Different Types of Zeolites on the Degradation Kinetics of Malathion Pesticide in Water

The study examined the effects of selected types of zeolites as an environmentally benign and friendly way to degrade, S-1, 2-bis (ethoxycarbonyl) ethyl O, O-dimethylphosphorodithioate (malathion), used as a model pesticide, from river water. The effect of the size of zeolite channels and dimensionality (such as 1D, 2D, and 3D), Si/Al ratio, and operating pH were studied to find a suitable type of zeolite and conditions to optimize the pesticide degradation. Mordenite (MOR (1D): Si/Al=6.83, and Si/Al=10.72), ferrierite (FER (2D): Si/Al=10.71), ZSM-5 (MFI (3D): Si/Al=6.83 and Si/Al=10.72) and USY (FAU (3D): Si/Al=2.77) zeolites were individually mixed with a water sample collected from Monjolinho River in São Carlos (SP), Brazil and the degradation trend studied. The results showed that all the zeolites accelerated the degradation of malathion. Nevertheless, lower zeolite Si/Al ratio and larger 3D channels or cavities had a positive influence on the degradation rate. The FAU zeolite presented the stronger degradation of the malathion with a half-life of 16.5 followed by ZSM-5 with 24.8, ferrierite with 29.7, and finally mordenite with 30.3 hours

Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial

Background In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. Methods and findings In a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76–1.28], p = 0.91); in serious (aHR = 0.99 [0.81–1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71–1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63–1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76–1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. Conclusions Although 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals. Trial registration ClinicalTrials.gov NCT01825031