PURPOSE:To explore changes in in-hospital mortality, admission to critical care unit (CCU) and clinical characteristics of patients hospitalized for COVID-19 in France. METHODS:Hospital discharge data were used to analyse outcomes during epidemic waves: W1 (January-July 2020), W2 (August 2020-June 2021), W3 (July-October 2021),W4 (November 2021-May 2022), W5 (June-September 2022). Join-point, logistic and survival regressions were used for the analyses. RESULTS:Overall, 502,532 patients were included. W3 patients were younger (median age: 61 years; interquartile-range: 44-76) and fewer than 10 % had a Charlson Comorbidity Index ≥ 3. The proportion of patients aged ≥ 75 years old was higher (59 %) during W5. Compared to W1, W3 patients had a higher risk of admission to CCU, adjusted odds ratios ranged from 1.18 (CI: 1.09-1.28) for < 45 years old to 1.30 (1.17-1.34) for ≥ 75 years old. In CCU the risk of death decreased by 47 % during W2 in < 45 years old, increased by 11 % during W4 for 45-74 years old, and increased by 13 % and 10 % during W2 and W3 respectively, for ≥ 75 years old. CONCLUSION:This analysis confirms the age as a major risk factor for adverse outcomes of COVID-19, and highlights the importance of hospital discharge data for future pandemics.

BACKGROUND:Lassa fever is one of the most important viral haemorrhagic fevers, yet post-discharge sequelae remain inadequately characterised. Previous studies have been limited by small sample sizes and unsystematic assessments. We aimed to describe post-discharge sequelae in Lassa fever survivors and explore the effect of disease severity on sequelae patterns. METHODS:LASCOPE was a prospective study of patients with PCR-confirmed Lassa fever hospitalised at Federal Medical Centre Owo, Owo, Nigeria, between April 23, 2018, and Feb 17, 2023. All patients who provided informed consent were included, with no age restriction. Severe disease was defined as the presence of at least one of the following during the acute phase: National Early Warning Score version 2 score of 7 or higher, Kidney Disease Improving Global Outcomes stage 2 or higher, or Lassa virus PCR Ct value of less than 25. At hospital discharge, follow-up of survivors was planned for day 60 after admission, or before that, based on medical need. A systematic symptom assessment was done at each visit. The main outcome was clinical remission, defined as complete absence of symptoms. Other outcomes were post-discharge death, symptom incidence, and prevalence of symptoms over time. Subgroup analyses were performed by age group (children aged <18 years or adults aged ≥18 years) and disease severity (severe or not severe). FINDINGS:Of 882 survivors (median age 32 years [IQR 22-46], 459 [52%] female and 423 [48%] male), post-discharge data were available for 807 (91%), with a total of 2603 person-months of follow-up. For three of 807 survivors with post-discharge information, only the vital status was collected. 736 (91%) of 807 reached clinical remission, with a median time to clinical remission of 19 days (95% CI 16-23) post discharge. The most frequently reported symptoms were asthenia (158 [20%] of 804), headache (148 [18%]), and post-exertional malaise (123 [15%]). Hearing symptoms were reported by only 17 (2%) of 804 survivors, which was substantially lower than previous studies. Disease severity did not affect time to remission. Six (1%) survivors died after hospital discharge. INTERPRETATION:Patient-reported symptoms suggest good recovery with few hearing or neurosensory disorders in most survivors of Lassa fever. Future research would benefit from extended follow-up periods and standardised diagnostic assessments, including objective audiometry, to further characterise the full spectrum of post-Lassa fever complications. FUNDING:Institut National de la Santé et de la Recherche Médicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, and French National Research Institute for Sustainable Development.

Ultraviolet germicidal irradiation (UVGI) has long been recognized for its ability to inactivate airborne pathogens under experimental conditions. However, despite strong in vitro evidence, randomized clinical evidence of its real-world effectiveness remains lacking. Nursing homes—where respiratory infections are a major cause of morbidity and mortality—represent a highly relevant setting to evaluate the preventive potential of UVGI. The RESPROTECT trial aims to assess whether continuous UVGI use in communal areas of nursing homes reduces the incidence of severe acute respiratory infections (ARIs) among residents. RESPROTECT is a multicenter, open cohort, quadruple-blind, cluster-randomized, crossover trial. A total of 848 UVGI devices were installed in communal living areas of 12 nursing homes in the Haute-Loire region, France. All devices are switched on, but some contain internal filters that deactivate UV light while remaining indistinguishable from the outside. Centers were randomized 1:1 into two groups: unfiltered UVGI devices active during period 1 (October 2024–April 2025), then filtered (inactive) during period 2 (October 2025–April 2026), or the reverse sequence. The primary outcome is the incidence of severe ARIs. Secondary outcomes include the incidence of ARIs of any grade, all-cause hospitalization or death, adverse events of interest (keratitis and erythema), antibiotic consumption, airborne and surface pathogen loads, and cost-effectiveness. All analyses will follow the intention-to-treat principle and use mixed-effects Poisson regression models with fixed effects for period and random effects for clusters, cluster-periods and individuals. RESPROTECT is one of the first large-scale blinded randomized trials to evaluate the clinical effectiveness of UVGI in preventing respiratory infections among elderly residents in nursing homes. It will complement recent findings from the PETRA trial (JAMA Intern Med 2025) and is designed to provide robust data on both clinical outcomes and environmental contamination. If UVGI proves effective, it could represent a practical, low-maintenance, and scalable infection-prevention strategy for high-risk institutional settings. French RCB identifier: RECHMIE-22-0003 - 2024-A00199-38. ClinicalTrials.gov Identifier: NCT06569160 (Registered on August 21, 2024). https://clinicaltrials.gov/study/NCT06569160.

Undernutrition and infectious diseases form a vicious cycle that poses a dual threat to vulnerable children in low- and middle-income countries. Integrating small-quantity lipid-based nutrient supplements (SQ-LNS) distribution into routine immunization services in children 6–23 months may act as both a nutritional intervention and as an incentive for increased vaccine uptake. We will conduct a two-arm superiority pragmatic parallel cluster-randomized controlled trial with baseline measures in 20 wards of Nguru and Karasuwa Local Government Areas, Yobe State, Northeast Nigeria. Wards will be randomly allocated 1:1 to either the standard National Program on Immunization (NPI) arm or the NutriVax arm, which combines NPI with SQ-LNS distribution. After up to 12 months of implementation, measles immunization coverage will be assessed at two levels: population-level coverage in children aged 12–23 months (primary outcome, endline cross-sectional survey) and individual-level coverage in children aged 6–12 months (key secondary outcome, longitudinal survey). Each cross-sectional survey (baseline and endline) will include 1560 participants. The longitudinal survey will enroll 600 participants. Sampling will use a multi-stage design with probability proportional to size and systematic random household selection. All outcomes will be analyzed by intention-to-treat. Qualitative interviews will assess feasibility and acceptability. Cost-efficiency differences between arms will be estimated using an incremental cost-efficiency ratio. To our knowledge, this is the first trial to evaluate whether a preventive nutrition supplement can also serve as an incentive to increase vaccination coverage. Findings will provide evidence to guide governments and donors in settings where high rates of undernutrition and low immunization coverage persist as major public health challenges. Protocol Number NCT06387511 (clinicaltrials.gov).

BACKGROUND:Despite tuberculosis being a well-known concern in patients with advanced human immunodeficiency virus (HIV), the STATIS trial, which focused on its management, highlighted significant mortality rates. Histoplasmosis, a fungal disease endemic in sub-Saharan Africa, presents with similar clinical manifestations as tuberculosis. Therefore, it may be prevalent and potentially responsible for deaths in patients with advanced HIV in this region. We conducted an ancillary study of the ANRS STATIS trial to provide the first prevalence estimates of histoplasmosis among individuals with advanced HIV in Côte d'Ivoire. METHODS:We analyzed urine samples from patients previously enrolled in the STATIS trial in Côte d'Ivoire. These ambulatory patients with newly diagnosed HIV infection, CD4+ T-cell counts <100/µL, and eligible for antiretroviral therapy (ART) were randomized to receive either systematic or test-guided tuberculosis treatment. We performed Histoplasma antigen enzyme immunoassay on their urine samples. RESULTS:The prevalence of Histoplasma antigenuria was 68/280 (24.3%; 95% CI: 19.5%-29.8%), including 52/280 (18.6%; 95% CI: 14.3%-23.7%) symptomatic patients. Of 22 tuberculosis cases documented at inclusion, 8 (36.4%) also had Histoplasma antigenuria. In patients who died within the 48-week follow-up, the prevalence of Histoplasma antigenuria was 15/42 (35.7%% 95% CI: 22.0%-52.0%) compared with 22.3% (95% CI: 17.3%-28.2%) in those surviving. These survivors had a higher body mass index, CD4+ T-cell count, and hemoglobin and platelet count than those who died. CONCLUSIONS:The prevalence of Histoplasma antigenuria was comparable to that of tuberculosis, and histoplasmosis was potentially responsible for preventable deaths. Prospective studies are needed to confirm these findings and promote screening strategies in sub-Saharan Africa.

Acute malnutrition (AM) causes large loss of life and disability in children in Africa. Researchers are testing innovative approaches to increase the efficiency of treatment programs This paper presents results of a cost-effectiveness analysis of one such program in the Democratic Republic of the Congo (DRC) based on a secondary analysis of a randomized controlled trial Optimizing Treatment for Acute Malnutrition (OptiMA), conducted in DRC in 2018-20. A total of 896 children aged 6-59 months with a mid-upper arm circumference (MUAC) <125 mm or with oedema were treated and followed for 6 months. The cost-effectiveness of OptiMA using ready-to-use therapeutic food (RUTF) at a tapered dose was compared with the standard national program in which severe cases (SAM) received RUTF proportional to weight, and moderate cases (MAM) were referred to another clinic for a fixed dose regimen of ready-to-use supplementary food. Cost analysis from the provider perspective used data collected during the trial and from administrative records. Statistical differences were derived using t-tests. The mean cost per enrolled child under OptiMA was $123 [95% confidence interval (CI): 114-132], not statistically different from the standard group [$127 (95%CI: 118-136), P = 0.549], while treatment success (i.e. recovery to MUAC > 125 mm and no relapse for 6 months) under OptiMA was 9% higher (72 vs 63%, P = 0.004). Among children with SAM at enrollment, there was no significant difference in treatment success between OptiMA and standard care (70 vs 62%, P = 0.12), but OptiMA's mean cost per enrolled child was 23% lower ($128 vs $166, P < 0.0001). OptiMA was more effective at preventing progression to SAM among those enrolled with MAM (5 vs 16%, P < 0.0001), with an incremental cost-effectiveness ratio of $234 per progression to SAM prevented. Overall, OptiMA had significantly better outcomes and was no more expensive than standard care. Its adoption could enable more children to be successfully treated in contexts where therapeutic food products are scarce.

BACKGROUND: Studies have shown that extended stays in Emergency Departments (ED) are detrimental to the health of elderly people. We aimed to compare Unscheduled Direct Admission (UDA) with admission after entry through the ED (EDA) for patients aged 75 and over, hospitalized in geriatrics at the Bordeaux University Hospital, between 2017 and 2019. METHODS: The study data were extracted from the hospital discharge database and the hospital information system. We compared in-hospital mortality and the modalities of discharge among UDA and EDA patients. A Cox proportional hazard model and a multinomial logistic regression were used to explore in-hospital mortality and the modalities of discharge, respectively. Missing data were handled by multiple imputation procedures. RESULTS: Between 2017 and 2019, 2,416 patients aged 75 and over were admitted for unscheduled hospitalization to geriatrics, including 669 (28%) UDA and 1,747 (72%) EDA. The UDA patients were younger (86.9 _vs_ 87.7 years old, p=0.002), had fewer acute diseases (43%_ vs_ 79%) and neurological diseases than EDA (24% _vs_ 30%, p=0.003). They also had a shorter length of stay on average (14.3 vs 15.9, p=0.0004). The UDA patients who were discharged alive more often returned home (83% _vs_ 75% for EDA), while EDA patients were more often transferred to rehabilitation (17% _vs_ 10% for UDA). The UDA patients, hospitalized for hematological diseases, were less likely to be transferred to rehabilitation (Odds Ratio: 0.10; 95% Confidence Interval [0.01-0.88]). The adjusted risk of death was not significantly different in UDA patients compared to EDA patients (HR = 1.00 [0.54;1.85]). CONCLUSIONS: The mortality and discharge rates did not differ between UDA and EDA patients. However, the length of hospital stay was longer for patients admitted through the Emergency Department. The UDA should be the admission pathway for elderly patients to relieve congestion in Emergency Departments.

Background Data on the presentation, management, and outcomes of Lassa fever (LF) in children are limited.Methods Description of the clinical and biological features, treatment, and outcomes of reverse transcriptase and polymerase chain reaction (RT-PCR)-confirmed LF in children aged under 15, enrolled in the LASsa fever clinical COurse and Prognostic factors in an Epidemic context (LASCOPE) prospective cohort study in Nigeria between April 2018 and February 2023.Results One hundred twenty-four children (aged under 12 months: 19; over 12 months: 105) were hospitalized with RT-PCR-confirmed LF. All received intravenous ribavirin. During follow-up, 99/124 (80%) had fever; 71/124 (57%) had digestive symptoms, vomiting (n = 56/122, 46%) and abdominal pain (n = 34/78 aged >= 5 years, 44%) more often than diarrhea (n = 19/124, 15%); 17/124 (14%) had hemorrhagic signs; 44/112 (39%) had a hematocrit lower than 25%, of whom 32/44 (73%) received transfusions; 44/88 (50%) developed hypotension; 18/112 (16.1%) developed kidney disease improving global outcome (KDIGO) >= 2 acute kidney injury; 10/112 (8.9%) had KDIGO 3 acute kidney failure; 4/124 (3.2%) underwent renal replacement therapy. Seven children died, including 4 aged under 12 months (case fatality rate: under 12 months-22%, 95% confidence interval (CI): 7%-48%; over 12 months-2.9%, 95% CI: 0.7%-8.7%). In univariable analysis, age (P = .003), impaired consciousness (P = .026), and Lassa RT-PCR Ct value (P = .006) were associated with Day 30 mortality.Conclusions The fatality rate for children over 12 months hospitalized with LF was lower than that previously reported for adults. Hypotension and acute kidney injury were the most frequent organ dysfunctions. Bleeding was relatively infrequent. Anemia and the need for transfusion were common, the relative contribution of ribavirin-induced hemolysis being unknown.

OBJECTIVES:Monitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. METHODS:ANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ-induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons. RESULTS:A total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (-71% in HIV-positive vs -33% in HIV-negative; P <0.001). The IP-10 plasma levels significantly decreased at W1 and W2 compared with baseline (P <0.0001); however, that decrease was less marked in participants with HIV. CONCLUSIONS:Our findings suggest that measuring IL-1Ra plasma levels with a standard enzyme-linked immunosorbent assay technique at baseline and then 1 week after TB treatment onset could help clinicians to quickly assess TB treatment response.

In severely immunosuppressed people with HIV, there is a clear benefit to systematically perform sputum Xpert and urine lipoarabinomannan tests prior to antiretroviral initiation as tuberculosis screening tests, not only in those with a positive World Health Organization 4-symptom screen. Background In people with human immunodeficiency virus (PWH), the World Health Organization-recommended tuberculosis (TB) 4-symptom screen (W4SS) targeting those who need molecular rapid testing may be suboptimal. We assessed the performance of different TB screening approaches in severely immunosuppressed PWH enrolled in the guided-treatment group of the STATIS trial (NCT02057796). Methods Ambulatory PWH with no overt evidence of TB and CD4 count <100 cells/mu L were screened for TB prior to antiretroviral therapy (ART) initiation with W4SS, chest radiograph (CXR), urine lipoarabinomannan (LAM) test, and sputum Xpert MTB/RIF (Xpert). Correctly and wrongly identified cases by screening approaches were assessed overall and by CD4 count threshold (<= 50 and 51-99 cells/mu L). Results Of 525 enrolled participants (median CD4 count, 28 cells/mu L), 48 (9.9%) were diagnosed with TB at enrollment. Among participants with a negative W4SS, 16% had either a positive Xpert, a CXR suggestive of TB, or a positive urine LAM test. The combination of sputum Xpert and urine LAM test was associated with the highest proportion of participants correctly identified as TB (95.8%) and non-TB cases (95.4%), with proportions equally high among participants with CD4 counts above or below 50 cells/mu L. Restricting the use of sputum Xpert, urine LAM test, or CXR to participants with a positive W4SS reduced the proportion of wrongly and correctly identified cases. Conclusions There is a clear benefit to perform both sputum Xpert and urine LAM tests as TB screening in all severely immunosuppressed PWH prior to ART initiation, not only in those with a positive W4SS.

Background: The assessment of iron status using a single biomarker of iron metabolism is not enough sensitive and specific to reliably diagnose iron deficiency associated with multiple comorbidities. The objective of this study was to describe the iron status of people living with HIV in sub-Saharan Africa using a multi-criteria approach based on the determination of blood ferritin, sTfR, CRP and the calculation of sTfR-F index. Methods: This study was conducted using a retrospective panel of 933 sera/plasmas. We determined serum ferritin concentration, serum sTfR concentration, and C-reactive protein (CRP) by immunoturbidimetry for each subject. The sTfR-F index was determined by calculating the sTfR/log ferritin ratio. The statistical test used was Chi2. Results: Regardless of the inflammatory syndrome, we determined 3.80%, 30.29%, and 42.70% iron deficiency based on the separate interpretation of ferritin concentration, sTfR, and sTfR-F calculation, respectively. We used those biomarkers in addition to CRP in an algorithm for the diagnosis of iron deficiency. Subjects without inflammatory syndrome, had iron deficiency of 2.89% (n = 26). Taking into account the presence of an inflammatory syndrome, the frequency obtained was n = 88 (9.78%). Overall, iron deficiency was diagnosed in 114 (12.67%) patients when we used the diagnostic algorithm. Conclusion: The use of diagnostic algorithms combining several biomarkers of iron metabolism and taking into account the presence or absence of an inflammatory syndrome is a good approach to detect a large number of iron deficiencies in a population. Therefore, an assessment of the effectiveness of different diagnostic algorithms is necessary.

Background: Current standard management of severe acute malnutrition uses ready-to-use therapeutic food (RUTF) at an increasing dosage as the child’s weight increases during recovery. Using RUTF at a gradually reduced dosage as the child recovers could optimise costs while achieving similar growth response.Methods: We conducted an open-label, non-inferiority, randomised controlled trial in the Democratic Republic of Congo. Children aged 6-59 months with a mid-upper arm circumference (MUAC) of less than 115 mm or a weight-for-height z-score (WHZ) of less than −3 or bipedal oedema were randomly assigned (1:1 ratio) using a specially developed software and random blocks (size was kept confidential), to either the current standard treatment (increasing the RUTF dose with increasing weight) or the OptiMA strategy (decreasing the RUTF dose with increasing weight and MUAC). The main endpoint was proportion of children who achieved recovery over the 6 months follow up period, as defined as meeting the following criteria for two consecutive weeks after a minimum of 4 weeks’ treatment: axillary temperature less than 37·5°C, no bipedal oedema, and anthropometric improvement (either MUAC 125 mm or greater or WHZ −1·5 or higher). We performed analyses on the intention-to-treat (all children) and per-protocol populations (participants who had a minimum prescription of 4 weeks’ RUTF, received at least 90% of the total amount of RUTF they were supposed to receive as per the protocol, and had a maximum interval of 6 weeks between any two visits in the 6-month follow-up). The non-inferiority margin was 10%. This trial is registered at ClinicalTrials.gov, and is now closed NCT03751475.Findings: Between July 22, 2019, and Jan 20, 2020, 491 children were randomly assigned, of whom 482 were analysed (240 in the standard group and 242 in the OptiMA group). In intention-to-treat analysis, 234 (98%) children in the standard group and 231 (96%) children in OptiMA recovered (difference 2·0%, 95% CI −2·0% to 6·4%). In the PP analysis, 234 (98%) children in the standard group and 228 (97%) in OptiMA recovered (difference 1·3%, 95% CI −2·3% to 5·1%). Interpretation: This non-inferiority trial treating children with MUAC of less than 115 mm or a WHZ of less than −3 or bipedal oedema with decreasing RUTF dose according to MUAC and weight proved to be non-inferior to the standard protocol in a highly food-insecure context in the Democratic Republic of Congo. These findings confirm the safety of RUTF dose reduction in children at a severe stage of acute malnutrition and point to benefits of an approach that could substantially increase access to treatment for children with acute malnutrition in sub-Saharan Africa.

Background Simplified approaches of acute malnutrition (AM) treatment have been conducted over the past 5 years intending to unify processes and increase coverage among children aged 6 to 59 months without medical complication. The Optimsing treatment for Acute Malnutrition (OptiMA) and the Combined Protocol for Acute Malnutrition Study (ComPAS) are mid-upper arm circumference (MUAC)-based approaches treating children with MUAC < 125 mm or oedema with one sole product—ready-to-use therapeutic food—at a gradually tapered doses. This trial aims to compare the OptiMA and ComPAS strategies to the standard nutritional protocol of Niger assessed by a favourable outcome in the treatment of uncomplicated AM at 6 months post-randomisation and in terms of recovery rate after treatment of uncomplicated SAM (WHZ < − 3 or MUAC < 115mm or oedema) and among the most vulnerable children (MUAC < 115mm or oedema). Methods A non-inferiority individually randomised controlled clinical trial was conducted at the primary health centres level and in the community in the Zinder region in Niger in March 2021. Participants are children aged 6–59 months attending outpatient health centres with MUAC < 125mm or oedema without medical complications. All participants are followed for 6 months. Simplified strategies propose a gradual reduction of RUTF according to MUAC and weight in OptiMA and MUAC only in ComPAS. Favourable outcome is compositely defined at 6 months post-inclusion as being alive, not acutely malnourished by the definition applied at inclusion and without any additional episode of AM throughout the 6-month observation period. Recovery is defined throughout the 6 months post-randomisation by a minimum of 4-week duration of treatment, an axillary temperature < 37.5°C, an absence of bipedal oedema and a MUAC ≥ 125 mm for two consecutive weeks. The sample size calculation required 567 children per arm for the main objective, 295 and 384 children per arm for the secondary objectives among SAM and MUAC < 115 mm children, respectively. Per-protocol and intention-to-treat analyses will be conducted for each outcome. Discussion This trial is intending to generate much-needed evidence on various simplified and optimised AM treatment approaches and to participate in reaching a consensus on such nutrition protocols. Trial registration ClinicalTrials.gov NCT04698070 . Registered on January 6, 2021

We report the association between pre‐antiretroviral therapy (pre‐ART) soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels and long‐term mortality in HIV‐infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial).

Introduction: The physiological status of a subject and the pathophysiology in some diseases might be under the influence of haptoglobin phenotype. The objective of this work was to determine the relationship between mortality from HIV/AIDS infection and haptoglobin phenotype in a black population in Côte d’Ivoire. Methods: The study was conducted from a retrospective panel of 933 sera/plasma from the previous workup of the ANRS 12136 TEMPRANO trial at month 0 of patients in deferred-ART arms. For each subject, we determined the serum haptoglobin concentration, haptoglobin phenotype, and other variables from patient files from the TEMPRANO trial database. Statistical tests used were Chi-2, Fischer, and Kruskal-Wallis tests for non-gaussian distribution. We used the Kaplan-Meier method for survival analysis. Results: The distributions of the haptoglobin phenotypes were 32.3% for Hp 1-1, 39.5% for Hp 2-1 and 27.2% for Hp 2-2. The blood haptoglobin concentration seemed to be associated with haptoglobin phenotypes (p-value > 5%). The survival rate at M30 and for an extended follow-up up to 6 years was independent of haptoglobin phenotype (p-value > 5%). Besides, the haptoglobin phenotypes do not appear to be associated with CD4+ T-cell count and with hemoglobin concentration. Conclusion: Haptoglobin phenotype seems to not impact the mortality of HIV/AIDS infection. However, given the antioxidant and immunomodulatory properties of some haptoglobin phenotypes, it would be relevant to seek out possible confounding factors indirectly associated with haptoglobin phenotypes and clinical or biological infection variables.

BACKGROUND:Global access to acute malnutrition treatment is low. Different programmes using different nutritional products manage cases of severe acute malnutrition and moderate acute malnutrition separately. We aimed to assess whether integrating severe acute malnutrition and moderate acute malnutrition treatment into one programme, using a single nutritional product and reducing the dose as the child improves, could achieve similar or higher individual efficacy, increase coverage, and minimise costs compared with the current programmes. METHODS:We conducted an open-label, non-inferiority, randomised controlled trial in the Democratic Republic of the Congo. Acutely malnourished children aged 6-59 months with a mid-upper-arm circumference (MUAC) of less than 125 mm or oedema were randomly assigned (1:1), using specially developed software and random blocks (size was kept confidential), to either the current standard strategy (one programme for severe acute malnutrition using ready-to-use therapeutic food [RUTF] at an increasing dose as weight increased, another for moderate acute malnutrition using a fixed dose of ready-to-use supplementary food [RUSF]) or the OptiMA strategy (a single programme for both severe acute malnutrition and moderate acute malnutrition using RUTF at a decreasing dose as MUAC and weight increased). The primary endpoint was a favourable outcome at 6 months, defined as being alive, not acutely malnourished as per the definition applied at inclusion, and with no further episodes of acute malnutrition throughout the 6-month observation period; the endpoint was analysed in the intention-to-treat (all children) and per-protocol populations (participants who had a minimum prescription of 4 weeks' RUTF, received at least 90% of the total amount of RUTF they were supposed to receive as per the protocol, or were prescribed RUSF rations for a minimum of 4 weeks [ie, minimum of 28 RUSF sachets], and had a maximum interval of 6 weeks between any two visits in the 6-month follow-up). The non-inferiority analysis (margin 10%) was to be followed by a superiority analysis (margin 0%) if non-inferiority was concluded. This trial is registered at ClinicalTrials.gov, NCT03751475, and is now closed. FINDINGS:Between July 22 and Dec 6, 2019, 912 children were randomly assigned; after 16 were excluded, 896 were analysed (446 in the standard group and 450 in the OptiMA group). In the intention-to-treat analysis, 282 (63%) of 446 children in the standard group and 325 (72%) of 450 children in the OptiMA group had a favourable outcome (difference -9·0%, 95% CI -15·9 to -2·0). In the per protocol analysis, 161 (61%) of 264 children in the standard group and 291 (74%) of 392 children in the OptiMA group had a favourable outcome (-13·2%, -21·6 to -4·9). INTERPRETATION:In this non-inferiority trial treating children with MUAC of less than 125 mm or oedema, decreasing RUTF dose according to MUAC and weight increase proved to be a superior strategy to the standard protocol in the Democratic Republic of the Congo. These results demonstrate the safety and benefits of an approach that could substantially increase access to treatment for millions of children with acute malnutrition in sub-Saharan Africa. FUNDING:Innocent Foundation and European Civil Protection and Humanitarian Aid Operations. TRANSLATION:For the French translation of the abstract see Supplementary Materials section.

Background: Data on HIV-1 controllers in Africa are scarce. We report the proportion of HIV-1 controllers in a group of adults prospectively monitored with frequent viral load measurements as part of a clinical trial in West Africa. Methods: For the Temprano trial, antiretroviral therapy (ART)-naive HIV-1 infected adults with no criteria for starting ART were randomized to start ART immediately or defer ART until the WHO starting criteria were met. Plasma viral load was measured every 6 months. The trial follow-up was 30 months. We considered all Temprano participants randomized to defer ART. Patients with all semestrial viral <2000 copies/ml and still off ART at month 30 were defined as HIV-1 controllers. Controllers with all viral loads <50 copies/ml were defined as elite controllers, the rest as viremic controllers. Results: Of the 1023 HIV-1-infected adults randomized in the Temprano deferred-ART group, 18 (1.8%) met the criteria for classification as HIV controllers, of whom seven (0.7%) were elite controllers and 11 (1.1%) viremic controllers. The HIV-1 controllers had low peripheral blood mononuclear cell HIV-1 DNA and low inflammatory marker levels. They maintained high CD4(+) cell count and percentages and had a low morbidity rate. Discussion: HIV controllers exist in Africa at a proportion close to that reported elsewhere. They represent a small fraction of all HIV-1-infected patients but raise important questions. Further studies should assess whether starting ART might represent more risk than benefit for some controllers, and where it does, how to identify these patients before they start ART.

The main objective was to compare the OptiMA strategy- ie.supplementing with ready-to-use therapeutic food at a gradually reduced doses- with the current national standard protocol. This non-inferiority, individually randomised controlled clinical trial was conducted in the Democratic Republic of Congo. Children 6–59 months with MUAC < 125 mm or weight-for-height Zscore< −3 or oedema and without medical complication were randomized to either OptiMA or standard arm and followed for 6 months. The main outcome was a binary composite indicator at 6-months post inclusion: child alive, not acutely malnourished per the study definition, and without an additional episode of acute malnutrition throughout the observation period. Non-inferiority was shown if the upper-bound of the 95% CI of the difference of proportion of favourable outcome between the two strategies was less than 10% in both intention-to-treat (ITT) and per-protocol (PP) analyses. Superiority (upper-bound of the 95% CI of this difference lower than 0%) was considered if non-inferiority was shown. Between July 2019 and July 2020, 981 children were enrolled. 896 children were included in the ITT analysis (450 OptiMA and 446 standard), 792 in the PP analysis. All children under OptiMA and 200 children in the standard arm were eligible for RUTF. ITT analysis showed 325 (72·2%) children had a favourable outcome under OptiMA versus 282 (63·2%) in the standard arm (difference: −9·2%, 95% CI: −15·9% to −2·0%). PP analysis was similar. Under OptiMA, weight and MUAC gain were greater (median weight gain, 1700 g versus 1600 g, P = 0·003 and median MUAC gain, 13 mm versus 12 mm, P = 0·012), and RUTF consumption was lower (median of 64 sachets versus 102 sachets, P = 0·018). There was no difference in hospitalization (10% OptiMA, 7% standard, P = 0·228) or mortality rates (0·2% in both arms). OptiMA was superior to the DRC standard protocol. It expanded access to RUTF, promoted improved anthropometry with lower RUTF consumption during treatment, and led to better outcomes at 6-months post inclusion. These results suggest benefits in giving smaller rations of RUTF at an earlier stage of malnutrition rather than larger rations only when children become severely malnourished. Innocent Foundation (London) European Civil Protection and Humanitarian Aid Operations (Brussels).

BACKGROUND:Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance.METHODS:In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30 months. Those in the deferred group who started ART were monitored for longer, until they had completed 30 months on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30 months after ART initiation.RESULTS:Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465 cells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10 copies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, P = 0.04) and a lower genotypic susceptibility score (P = 0.04).CONCLUSIONS:Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited.

The main secondary objective of OptiMA-DRC trial was to compare the OptiMA strategy, ie.supplementing with one product, ready-to-use therapeutic food at a gradually reduced doses, with the current national nutritionnal standard protocol in children with uncomplicated severe acute malnutrition (SAM) at inclusion (MUAC < 115 mm or WHZ< −3 or oedema) in both arms. This non-inferiority, individually randomised controlled clinical trial was conducted in Kasai province, Democratic Republic of Congo (DRC) between July 2019 and July 2020. Children 6–59 months with MUAC < 115 mm or weight-for-height Zscore (WHZ)< −3 or oedema and without medical complication were randomized to either the OptiMA or standard arm and followed for 6 months.. Recovery was defined as MUAC > 125 mm for OptiMA and MUAC > 125 mm or WHZ >−1.5 for the standard arm, and absence of oedema, for two consecutive weeks in treatment with a 4-week minimum stay, and at any time during 6-months post-inclusion. Non-inferiority was shown if the upper-bound of the 95%CI of the difference of proportion of recovery between the two strategies was less than 10% in both intention-to-treat (ITT) and per-protocol (PP) analyses. Superiority (upper-bound of the 95%CI of this difference lower than 0%) was considered if non-inferiority was shown. Overall, 482 children with uncomplicated SAM were included in ITT analysis (242 OptiMA, 240 standard). At 6 months, 231 (95·5%) children recovered under OptiMA versus 234 (97·5%) under standard protocol (difference −2·0%, 95%CI: −1·96% to 6·4%). PP analysis was similar. There was no difference in hospitalization (11% OptiMA, 12% standard, P = 0·887) or mortality rates (0·2% both arms). Under OptiMA, weight and MUAC gains in recovered children (N = 465) were greater (median weight gain, 1400g versus 1200g, P< 0·001; median MUAC gain, 14 mm versus 11 mm, P < 0·001) and RUTF consumption (sachets) was lower (median 74 versus 112, P < 0·001). Children with uncomplicated SAM recovered as well under OptiMA as under the DRC standard protocol. Gradual RUTF reduction may allow for increased nutrition program coverage by better allocating available resources. Innocent Foundation (London) European Civil Protection and Humanitarian Aid Operations (Brussels).