Differences in HIV cure clinical trial preferences of French people living with HIV and physicians in the ANRS-APSEC study: a discrete choice experiment.

INTRODUCTION: Despite the advent of HIV cure-related clinical trials (HCRCT) for people living with HIV (PLWH), the risks and uncertainty involved raise ethical issues. Although research has provided insights into the levers and barriers to PLWH and physicians' participation in these trials, no information exists about stakeholders' preferences for HCRCT attributes, about the different ways PLWH and physicians value future HCRCT, or about how personal characteristics affect these preferences. The results from the present study will inform researchers' decisions about the most suitable HCRCT strategies to implement, and help them ensure ethical recruitment and well-designed informed consent. METHODS: Between October 2016 and March 2017, a discrete choice experiment was conducted among 195 virally controlled PLWH and 160 physicians from 24 French HIV centres. Profiles within each group, based on individual characteristics, were obtained using hierarchical clustering. Trade-offs between five HCRCT attributes (trial duration, consultation frequency, moderate (digestive disorders, flu-type syndrome, fatigue) and severe (allergy, infections, risk of cancer) side effects (SE), outcomes) and utilities associated with four HCRCT candidates (latency reactivation, immunotherapy, gene therapy and a combination of latency reactivation and immunotherapy), were estimated using a mixed logit model. RESULTS: Apart from severe SE - the most decisive attribute in both groups - PLWH and physicians made different trade-offs between HCRCT attributes, the latter being more concerned about outcomes, the former about the burden of participation (consultation frequency and moderate SE). These different trades-offs resulted in differences in preferences regarding the four candidate HCRCT. PLWH significantly preferred immunotherapy, whereas physicians preferred immunotherapy and combined therapy. Despite the heterogeneity of characteristics within the PLWH and physician profiles, results show some homogeneity in trade-offs and utilities regarding HCRCT. CONCLUSIONS: Severe SE, not outcomes, was the most decisive attribute determining future HCRCT participation. Particular attention should be paid to providing clear information, in particular on severe SE, to potential participants. Immunotherapy would appear to be the best HCRCT candidate for both PLWH and physicians. However, if the risk of cancer could be avoided, gene therapy would become the preferred strategy for the latter and the second choice for the former.

Renunciation of health care by people living with HIV in France is still associated with discrimination in health-care services and social insecurity - results from the ANRS-VESPA2 survey.

BACKGROUND: This study aimed to estimate the frequency of renunciation of health care among people living with HIV (PLHIV) in France, including health care unrelated to HIV, and to characterize associated socioeconomic and psychosocial risk factors. METHODS: The cross-sectional ANRS-VESPA2 survey was conducted on adult PLHIV attending French hospitals in 2011. Correlates of health-care renunciation in the 12 months before the survey were assessed through logistic modelling. RESULTS: Among the 3,020 PLHIV included in the sample, 17% declared health-care renunciation during the preceding year and 42% had a high level of social insecurity. During the previous 2 years, 8% and 11%, respectively, were discriminated against by medical staff and family. In multivariate analysis, positive associations were found between health-care renunciation and a high level of social insecurity (adjusted odds ratio [95% CI] 3.44 [2.54, 4.65]; P<0.001), having children (1.52 [1.10, 2.10]; P=0.01), smoking tobacco (1.50 [1.13, 1.98]; P=0.01), discrimination by medical staff (1.53 [1.22, 2.29]; P=0.04) or family (2.48 [1.75, 3.52]; P<0.001), major depressive episodes (1.46 [1.02, 2.09]; P=0.04), past or current drug injection (1.54 [1.03, 2.30]; P=0.04), and younger age (0.98 [0.97, 1.00]; P=0.03). Health-care renunciation was also negatively associated with HIV diagnosis after 1996 (1996-2002: 0.64 [0.46, 0.90]; P=0.01; ≥2003: 0.56 [0.40, 0.77]; P=0.001). CONCLUSIONS: In spite of universal health insurance in France, barrier- and refusal-renunciation of health care by PLHIV remain frequent. Poor psychosocial outcomes and discrimination by families and health-care providers compound the negative effect of social insecurity on health-care seeking in this population. To ensure optimal medical care, strategies are needed to prevent discrimination against PLHIV in health-care services. Special attention must be provided to patients experiencing social insecurity.

Subclinical inflammation affects iron and vitamin A but not zinc status assessment in Senegalese children and Cambodian children and women.

OBJECTIVE: To assess the impact of the acute-phase response (APR) during inflammation on Fe, Zn and vitamin A biomarkers to allow accurate evaluation of micronutrient status in populations. DESIGN: Ferritin (FER), soluble transferrin receptor (TfR), retinol-binding protein (RBP), Zn, α1-acid glycoprotein and C-reactive protein concentrations were measured. Correction factors (CF) for each biomarker were calculated as the ratio for groups at different stages of inflammation v. the reference group without inflammation.Setting/SubjectsSenegalese (n 594) and Cambodian schoolchildren (n 2471); Cambodian women of reproductive age (n 2117). RESULTS: TfR was higher during the incubation phase (CF=1·17) and lower during early and late convalescence (CF=0·87 and 0·78). FER was higher during all phases (CF=0·83, 0·48 and 0·65, respectively). RBP was higher during incubation (CF=0·88) and lower during early convalescence (CF=1·21). No effect of inflammation on Zn status was found. CONCLUSIONS: Inflammation led to overestimation of Fe status and underestimation of vitamin A status. The response of the biomarker for vitamin A status to inflammation depended on the vitamin A status of the populations. Surprisingly, the assessment of Zn status was hardly affected by inflammation. Different phases of the APR had opposite effects on the assessment of Fe status using TfR. More research is needed to define the correct methods to adjust for inflammation in nutritional studies.

Cognitive Performance and Iron Status are Negatively Associated with Hookworm Infection in Cambodian Schoolchildren.

Soil-transmitted helminth (STH) infection has been associated with lower cognitive performance of schoolchildren. To identify pathways through which STH infection might affect school performance, baseline data from a large rice-fortification trial in Cambodian schoolchildren were used to investigate associations between STH infection, micronutrient status, anemia, and cognitive performance. Complete data on anthropometry, cognitive performance, and micronutrient status were available for 1,760 schoolchildren, 6-16 years of age. STH infection was identified using Kato-Katz, whereas cognitive performance was assessed using Raven's Colored Progressive Matrices (RCPM), block design, and picture completion. STH infection was found in 18% of the children; almost exclusively hookwork infection. After adjusting for age and gender, raw cognitive test scores were significantly lower in hookworm-infected children (-0.65; -0.78; -2.03 points for picture completion, RCPM, and block design, respectively; P < 0.05 for all). Hookworm infection was associated with iron status (total body iron), but not with vitamin A and zinc status, nor with inflammation or anthropometry. Body iron was negatively associated with increased intensity of hookworm infection (R = 0.22, P < 0.001). Hookworm infection in Cambodian schoolchildren was associated with lower cognitive performance, an effect most likely mediated through lower body iron. Interventions that are more effective against hookworm infection are needed to contribute to better health and improvement of cognitive performance.

Current MUAC Cut-Offs to Screen for Acute Malnutrition Need to Be Adapted to Gender and Age: The Example of Cambodia.

BACKGROUND: Early identification of children <5 yrs with acute malnutrition is a priority. Acute malnutrition is defined by the World Health Organization as a mid-upper-arm circumference (MUAC) <12.5 cm or a weight-for-height Z-score (WHZ) <-2. MUAC is a simple and low-cost indicator to screen for acute malnutrition in communities, but MUAC cut-offs currently recommended by WHO do not identify the majority of children with weight-for-height Z-score (<-2 (moderate malnourished) or r<-3 (severe malnourished). Also, no cut-offs for MUAC are established for children >5 yrs. Therefore, this study aimed at defining gender and age-specific cut-offs to improve sensitivity of MUAC as an indicator of acute malnutrition. METHODS: To establish new age and gender-specific MUAC cut-offs, pooled data was obtained for 14,173 children from 5 surveys in Cambodia (2011-2013). Sensitivity, false positive rates, and areas under receiver-operator characteristic curves (AUC) were calculated using wasting for children <5yrs and thinness for children ≥5yrs as gold standards. Among the highest values of AUC, the cut-off with the highest sensitivity and a false positive rate ≤33% was selected as the optimal cut-off. RESULTS: Optimal cut-off values increased with age. Boys had higher cut-offs than girls, except in the 8-10.9 yrs age range. In children <2yrs, the cut-off was lower for stunted children compared to non stunted children. Sensitivity of MUAC to identify WHZ<-2 and <-3 z-scores increased from 24.3% and 8.1% to >80% with the new cut-offs in comparison with the current WHO cut-offs. CONCLUSION: Gender and age specific MUAC cut-offs drastically increased sensitivity to identify children with WHZ-score <-2 z-scores. International reference of MUAC cut-offs by age group and gender should be established to screen for acute malnutrition at the community level.

Impact of Multi-Micronutrient Fortified Rice on Hemoglobin, Iron and Vitamin A Status of Cambodian Schoolchildren: a Double-Blind Cluster-Randomized Controlled Trial.

In Cambodia, micronutrient deficiencies remain a critical public health problem. Our objective was to evaluate the impact of multi-micronutrient fortified rice (MMFR) formulations, distributed through a World Food Program school-meals program (WFP-SMP), on the hemoglobin concentrations and iron and vitamin A (VA) status of Cambodian schoolchildren. The FORISCA-UltraRice+NutriRice study was a double-blind, cluster-randomized, placebo-controlled trial. Sixteen schools participating in WFP-SMP were randomly assigned to receive extrusion-fortified rice (UltraRice Original, UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. Four additional schools not participating in WFP-SMP were randomly selected as controls. A total of 2440 schoolchildren (6-16 years old) participated in the biochemical study. Hemoglobin, iron status, estimated using inflammation-adjusted ferritin and transferrin receptors concentrations, and VA status, assessed using inflammation-adjusted retinol-binding protein concentration, were measured at the baseline, as well as at three and six months. Baseline prevalence of anemia, depleted iron stores, tissue iron deficiency, marginal VA status and VA deficiency were 15.6%, 1.4%, 51.0%, 7.9%, and 0.7%, respectively. The strongest risk factors for anemia were hemoglobinopathy, VA deficiency, and depleted iron stores (all p < 0.01). After six months, children receiving NutriRice and URN had 4 and 5 times less risk of low VA status, respectively, in comparison to the placebo group. Hemoglobin significantly increased (+0.8 g/L) after three months for the URN group in comparison to the placebo group; however, this difference was no longer significant after six months, except for children without inflammation. MMFR containing VA effectively improved the VA status of schoolchildren. The impact on hemoglobin and iron status was limited, partly by sub-clinical inflammation. MMFR combined with non-nutritional approaches addressing anemia and inflammation should be further investigated.

Stunting, poor iron status and parasite infection are significant risk factors for lower cognitive performance in Cambodian school-aged children.

BACKGROUND: Nutrition is one of many factors affecting the cognitive development of children. In Cambodia, 55% of children <5 y were anemic and 40% stunted in 2010. Currently, no data exists on the nutritional status of Cambodian school-aged children, or on how malnutrition potentially affects their cognitive development. OBJECTIVE: To assess the anthropometric and micronutrient status (iron, vitamin A, zinc, iodine) of Cambodian schoolchildren and their associations with cognitive performance. METHODS: School children aged 6-16 y (n = 2443) from 20 primary schools in Cambodia were recruited. Anthropometry, hemoglobin, serum ferritin, transferrin receptors, retinol-binding protein and zinc concentrations, inflammation status, urinary iodine concentration and parasite infection were measured. Socio-economic data were collected in a sub-group of children (n = 616). Cognitive performance was assessed using Raven's Colored Progressive Matrices (RCPM) and block design and picture completion, two standardized tests from the Wechsler Intelligence Scale for Children (WISC-III). RESULTS: The prevalence of anemia, iron, zinc, iodine and vitamin A deficiency were 15.7%; 51.2%, 92.8%, 17.3% and 0.7% respectively. The prevalence of stunting was 40.0%, including 10.9% of severe stunting. Stunted children scored significantly lower than non-stunted children on all tests. In RCPM test, boys with iron-deficiency anemia had lower scores than boys with normal iron status (-1.46, p<0.05). In picture completion test, children with normal iron status tended to score higher than iron-deficient children with anemia (-0.81; p = 0.067) or without anemia (-0.49; p = 0.064). Parasite infection was associated with an increase in risk of scoring below the median value in block design test (OR = 1.62; p<0.05), and with lower scores in other tests, for girls only (both p<0.05). CONCLUSION: Poor cognitive performance of Cambodian school-children was multifactorial and significantly associated with long-term (stunting) and current nutritional status indicators (iron status), as well as parasite infection. A life-cycle approach with programs to improve nutrition in early life and at school-age could contribute to optimal cognitive performance.