C-reactive protein is more suitable than Serum Amyloid A to monitor crises and attack-free periods in Systemic Auto-Inflammatory Diseases.

BACKGROUND: With their broad presentations and no global biomarker to discriminate crises and attack-free periods, Systemic Auto-Inflammatory Diseases (SAID) are difficult to manage. This study assessed Serum Amyloid A (SAA), C-reactive protein (CRP) and serum calprotectin as potential biomarkers to monitor patients with SAID. METHOD: SAA (already studied in Familial Mediterranean Fever (FMF)), CRP and serum calprotectin were measured on SAID adult patients from Juvenile Inflammatory Rheumatism (JIR) cohort during their follow-up visits between 2020 and 2022. Crises and attack-free periods were clinically determined. RESULTS: 96 measures, mainly from FMF (43 %) and Unclassified SAID (USAID) (37 %) patients were included. Using ROC curves, a threshold with sensitivity and specificity of/over 75 % was determined for SAA (9 mg/L) and CRP (9 mg/L) but not for serum calprotectin, not investigated further. With this threshold, the results were similar in FMF and USAID patients' subgroups. SAA and CRP showed a positive correlation with crises and attack-free periods in SAID patients (r = 0.4796, p < 0.001 and r = 0.5525, p < 0.001, respectively) as in FMF and USAID patients, with no significant difference between both markers in diagnosis value and ROC curves Area Under Curve (AUC) (p = 0.32). Only the CRP results were not influenced by obesity. CONCLUSION: SAA and CRP can discriminate crisis and attack-free periods in our cohort of SAID patients mainly composed of FMF and USAID patients. However, only CRP can be used regardless of body mass index. It is the first report of common biomarkers for all SAID, including USAID patients, with CRP widely accessible in routine worldwide.

Biological markers of adipose tissue: Adipokines.

We currently have a large sum of clinical and experimental data documenting the involvement of numerous adipokines in the maintenance of energy homeostasis in healthy individuals and their dysregulation in diseases such as obesity, metabolic syndrome or type 2 diabetes. Despite the impressive discoveries made in this field over many years, much remains to be done before understanding all the physiological and pathological implications, and hoping for the development of other effective and safe therapeutic strategies. Two original adipokines will be taken as examples to illustrate these remarks, chemerin and neuregulin 4.

Prognostic mortality factors in advanced light chain cardiac amyloidosis: A prospective cohort study.

AIMS: Predicting mortality in severe AL cardiac amyloidosis is challenging due to elevated biomarker levels and limited thresholds for stratifying severe cardiac damage. METHODS AND RESULTS: This prospective, observational, cohort study included de novo, confirmed cardiac AL amyloidosis patients at the Henri Mondor National Reference Centre. The goal was to identify predictors of mortality to enhance prognostic stratification and improve informed decision-making regarding therapy. Over the 12-year study period, among the 233 patients included, 133 were NYHA III-IV and 179 Mayo 2004 III. The independent predictors for mortality identified were hsTnT, NT-proBNP, cardiac output, and conjugated bilirubin. A novel prognostic, conditional stratification, Mondor amyloidosis cardiac staging (MACS) was developed with biomarker cut-off values for Stage 1: hsTnT ≤ 107 ng/L and NT-proBNP ≤ 3867 ng/L (n = 77; 33%); for stage 2 NT-proBNP > 3867 ng/L (n = 72; 30%). For stage 3, if troponin >107 ng/L, regardless of NT-proBNP then CB 4 µmol/L, was added (n = 41; 17.5%) and stage 4: CB > 4 µmol/L (n = 43; 18.5%). The median overall survival was 8 months 95% CI [2-24]. At 1 year, 102 (44%) patients died and the Kaplan-Meier median survival with MACS Stage 1 was not reached, while stage 2 was 15.2 months (95% CI [11-18]) and stage 3, 6.6 months (95% CI [1-13]). Notably, among European stage II patients, 17.1%, n = 8 were MACS stage 3 and European stage IIIb 21.4% (n = 23) were MACS stage 4. Importantly, among European stage IIIb patients 42.2% (n = 29) were classified MACS stage 4 and 12.5% n = 9 were only MACS stage 2. CONCLUSIONS: The Mondor prognostic staging system, including conjugate bilirubin may significantly improve prognostic stratification for patients with severe cardiac amyloidosis.

Serum Versus Fecal Calprotectin Levels in Patients with Severe Obesity Before and 6 Months After Roux-Y-Gastric Bypass: Report of the Prospective Leaky-Gut Study.

INTRODUCTION: Obesity is associated with low-grade inflammation, including intestinal inflammation based on fecal or serum calprotectin (FC-SC) measurement. Roux-en-Y gastric bypass (RYGB) improves obesity-related parameters. However, the association between FC-SC levels and postoperative course and the link with metabolic and inflammatory phenotypes before and after RYGB remains unclear. METHODS: We determined SC levels in 48 patients before (T0) and 6 months after (T6M) RYGB. We then analyzed postoperative changes in FC-SC levels and the relationship with inflammation and metabolic status. RESULTS: Twenty-three patients (48%) had elevated SC levels (˃2.9 µg/mL) at T0 and T6M. Six of 29 patients (20.7%) had elevated FC concentrations (>50 µg/g) at T0 vs. 16 of 17 patients (94.1%) at T6M (p=0.006). At T0, FC levels correlated with BMI (Rho=0.63; p=0.001) and systemic inflammation (CRP: Rho=0.66, p=0.0006; IL-6: Rho=0.48, p=0.03; haptoglobin: Rho=0.75; p= 0.0006). SC tended to be positively associated with triglyceride levels (Rho=0.34; p=0.08), BMI (Rho=0.34; p=0.08), and inflammatory markers (CRP: Rho=0.33; p=0.09; IL-6: Rho=0.36; p=0.06). FC levels were associated with increased jejunal IL-17+CD8+ T-cell densities (Rho:0.90; p=0.0002). FC and SC were correlated together at T0 (Rho=0.83; p<0.001) but not at T6M. At T6M, SC decreased by 53.6%, whereas FC increased by 79.7%. SC and FC were not associated with any of the variables studied at T6M. CONCLUSION: FC is a surrogate marker of systemic and intestinal inflammation and adiposity, whereas SC only tends to correlate with systemic inflammation. At 6 months after RYGB, SC-based systemic inflammation decreased, whereas FC-based intestinal inflammation increased. FC and SC levels follow different trajectories and are unrelated to improvements following bariatric surgery.

[Impact of voxelotor on hemoglobin electrophoretic and chromatographic profiles]. / Conséquences du traitement par voxelotor sur les profils électrophorétiques et chromatographiques de l'hémoglobine.

Voxelotor (GBT440, OXBRYTA®) appeared recently as one of the possible treatments for sickle cell disease. This molecule, by binding the alpha globin of hemoglobin, causes hyperaffinity of the latter for oxygen and reduces its polymerization properties. Several therapeutic trials have been able to show its effectiveness on certain aspects of sickle cell disease; thus, the french HAS (High Authority of Health) college issued an early access authorization and, since 2021, this treatment can be offered to patients under a temporary authorization for use. Consequently, the laboratories that carry out the biological monitoring of sickle cell patients will be confronted with new profiles characteristic of the presence of hemoglobin combined with GBT440. This work presents a collection of images obtained by different techniques: HPLC, capillary electrophoresis, isoelectrofocusing, alkaline gel and acid agar gel electrophoresis in transfused or non-transfused sickle cell disease patients. The ability to observe the presence of GBT440 by these analyzes could be useful in order to characterize the therapeutic follow-up of patients.

Screening HIV Patients at Risk for NAFLD Using MRI-PDFF and Transient Elastography: A European Multicenter Prospective Study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a growing concern in the aging population with human immunodeficiency virus (HIV). Screening for NAFLD is recommended in patients with metabolic risk factors or unexplained transaminitis. This study aimed to prospectively assess the prevalence and associated factors of liver steatosis and advanced fibrosis (AF) in HIV-monoinfected patients at risk of NAFLD. METHODS: We conducted a multicenter study in HIV-monoinfected patients, nonexcessive drinkers with metabolic syndrome, and/or persistently elevated liver enzymes, and/or clinical lipodystrophy. All participants had magnetic resonance imaging proton density fat fraction (MRI-PDFF), Fibroscan/controlled attenuation parameter (CAP), and cytokine and genetic analysis. RESULTS: From March 2014 to November 2015, we enrolled 442 participants and analyzed 402: male (85%); median age, 55 years (interquartile range [IQR], 50-61 years); body mass index, 27.0 kg/m2 (IQR, 23.6-28.7 kg/m2); metabolic syndrome (67%); and CD4 cell count, 630/mm3 (IQR, 510-832/mm3). Overall 257 of 402 (64%) had NAFLD (MRI-PDFF ≥5%). Among them, 11.3% had a liver stiffness ≥9.6 kPa, suggestive of AF. Multivariable analysis identified 7 factors of steatosis: high CD4-cell count (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.92-8.51), high leptin level (OR, 2.12; 95% CI, 1.14-3.93), non-CC PNPLA3s738409 genetic polymorphism (OR, 1.92; 95% CI, 1.11-3.33), low high-density lipoprotein (OR, 1.83; 95% CI, 1.03-3.27), high triglycerides (OR, 1.48; 95% CI, 1.18-1.84), elevated alanine transaminase (OR, 1.23; 95% CI, 1.16-1.31), and hyper ferritinemia (OR, 1.05; 95% CI, 1.03-1.07). Two factors were associated with AF: high body mass index (OR, 1.23 ; 95% CI, 1.07-1.42 ; P = .005, and elevated aspartate aminotransferase (OR, 1.03; 95% CI, 1.01-1.05; P = .001). Using MRI-PDFF as a reference, CAP (best cutoff, 280 dB/m) had good accuracy (area under the receiver operating characteristic curve = 0.86; 95% CI, 0.82-0.90) for the diagnosis of moderate to severe steatosis. CONCLUSIONS: In a large cohort of HIV-moninfected patients at risk of NAFLD, steatosis is present in two-thirds of cases, and around 10% have AF. The CAP technique is accurate for screening steatosis in this population.

Role of non-invasive methods in detecting liver impairment in familial Mediterranean fever adult patients with persistent hepatic cytolysis.

Familial Mediterranean fever (FMF) patients may have hepatic cytolysis, although its origin is not formally elucidated. We aimed to evaluate liver involvement in familial Mediterranean fever (FMF) using non-invasive methods. All adult FMF patients harboring two non-ambiguous mutations of the MEFV gene with hepatic cytolysis were identified in a French tertiary adult center for FMF. Liver impairment was explored with FibroMax (a non-invasive method to estimate hepatic steatosis, necrosis, inflammation and fibrosis) and liver ultrasound. Among 520 FMF adult patients, 43 had persistent hepatic cytolysis and 20 patients were included (11 women, median age at inclusion: 49.5 years). According to the FibroMax results, patients were classified as having steatosis, fibrosis, and possible or definite nonalcoholic steato-hepatitis in 10 (50%), 9 (45%) and 7 (35%) of cases, respectively. The score of steatosis did not seem associated with the usual metabolic risk factors. No significant association was found between the cumulated dose of colchicine and any of the scores included in FibroMax. In adult FMF patients with persistent hepatic cytolysis, steatosis is the first cause to consider even in the absence of usual metabolic risk factors, suggesting other mechanisms. Colchicine did not seem to be involved in this toxicity.

Acute Kidney Injury in Critically-Ill COVID-19 Patients.

Purpose: Acute kidney injury (AKI) is common in patients with COVID-19, however, its mechanism is still controversial, particularly in ICU settings. Urinary proteinuria profile could be a non-invasive tool of interest to scrutinize the pathophysiological process underlying AKI in COVID-19 patients. Material and Methods: We conducted a retrospective study between March 2020 and April 2020. All patients with laboratory-confirmed COVID-19 and without end-stage kidney disease requiring renal replacement therapy before ICU admission were included. Our objectives were to assess the incidence and risk factors for AKI and to describe its clinical and biological characteristics, particularly its urinary protein profile. Results: Seventy patients were included; 87% needed mechanical ventilation and 61% needed vasopressor during their ICU stay; 64.3% of patients developed AKI and half of them needed dialysis. Total and tubular proteinuria on day 1 were higher in patients with AKI, whereas glomerular proteinuria was similar in both groups. The main risk factor for AKI was shock at admission (OR = 5.47 (1.74−17.2), p < 0.01). Mortality on day 28 was higher in AKI (23/45, 51.1%) than in no-AKI patients (1/25, 4%), p < 0.001. Risk factors for 28-days mortality were AKI with need for renal replacement therapy, non-renal SOFA score and history of congestive heart failure. Conclusions: AKI is common in COVID-19 patients hospitalized in ICU; it seems to be related to tubular lesions rather than glomerular injury and is related to shock at ICU admission.

Interleukins in adipose tissue: Keeping the balance.

The role of the immune system is to defend the host and preserve the functionality in response to stress. This function is not limited to infection or injury as it also plays a role in the response to overnutrition. Indeed, low-grade chronic activation of the immune system associated with overnutrition may be deleterious, contributing importantly to diabetes and long-term complications, such as cardiovascular disorders. Increasing evidence shows that adipose tissue participates in the obesity-related inflammatory response and that interleukins are one of the key players, either as a pro-inflammatory response to the metabolic dysregulation or to restore homeostasis. The crosstalk between adipocytes and immune cells through some important interleukins and their role in metabolic disruption is the topic of this review.

Combinatorial, additive and dose-dependent drug-microbiome associations.

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.

Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc.

OBJECTIVE: To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease inhibitor regimen to raltegravir/maraviroc. DESIGN: Sub-study of the ANRS157 ROCnRAL study with the investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end. METHODS: We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used the Wilcoxon-paired test. RESULTS: The patients (n = 8) were mainly male (7/8), aged (mean ±â€Šstandard error of the mean) 54.9 ±â€Š1.2 years, BMI 26.1 ±â€Š1.2 kg/m2, CD4+ 699 ±â€Š56 cells/mm3, all viral load (VL) <50 copies/ml. After a follow-up of 6 ±â€Š0.5 months, all PLWH remained with VL <50 copies/ml. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P = 0.1). Among the 16 094 RNA transcripts, 458 genes were up-regulated and 244 were down-regulated. Analyses of the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed. CONCLUSION: After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size. Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, the immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.

Prevalence of Silent Atherosclerosis and Other Comorbidities in an Outpatient Cohort of Adults Living with HIV: Associations with HIV Parameters and Biomarkers.

People living with HIV (PLWH) are at risk of noninfectious comorbidities. It is important to individualize those at higher risk. In a single-center cohort of PLWH, we performed a cross-sectional analysis of comorbidities, diagnosed according to standard procedures. The primary endpoint was the prevalence of subclinical carotid/coronary atherosclerosis. Secondary endpoints were its association with selected inflammatory/immune activation biomarkers and with other comorbidities. Associations were examined by using Chi-square or Fisher's exact test for categorical variables and Student or Wilcoxon tests for quantitative variables, and a stepwise multivariate logistical model was performed for further exploration. Among 790 participants [median age: 49.8 years (interquartile range, IQR: 44.5-55.6), 77.1% males, median CD4: 536/mm3 (IQR: 390-754), 83.6% with undetectable viral load], asymptomatic atherosclerosis was found in 26% and was associated in multivariate analysis with older age, longer known duration of infection, higher sCD14, and lower adiponectin levels. Hypertension was found in 33.5% of participants, diabetes in 19.4%, renal impairment in 14.6%, elevated low-density lipoprotein-cholesterol in 13.3%, elevated triglyceride/high-density lipoprotein (HDL)-cholesterol ratio in 6.6%, and osteoporosis in 7.9%. The presence of two or more comorbidities was found in 42.1% of participants and was associated in multivariate analysis with older age and longer exposure to antiretrovirals. Comorbidities were diversely associated with biomarkers: osteoporosis with higher IL-6, renal impairment with higher sCD14, hypertension with higher D-dimer, diabetes and elevated triglyceride/HDL-cholesterol ratio both with lower adiponectin and lower 25-hydroxyvitamin D. Asymptomatic atherosclerosis and multimorbidity were frequent in a cohort of middle-aged, well-controlled, PLWH and were associated with traditional and HIV-specific factors. Associations between morbidities and inflammatory/immune activation biomarkers were diverse.

Plasma total adiponectin and changes in renal function in a cohort from the community: the prospective Data from an Epidemiological Study on the Insulin Resistance Syndrome study.

BACKGROUND: High adiponectin levels are associated with diabetic nephropathy. Nevertheless, it is not known whether plasma adiponectin is associated with renal function decline in the general population. We evaluated whether adiponectin concentrations were associated with changes in renal function in a community cohort, the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. METHODS: Plasma adiponectin concentrations were measured in a random sample of 3284 people from the DESIR study, a 9-year prospective cohort from the general population. Data were analysed for three endpoints during follow-up: incidence of Stage 3 chronic kidney disease (CKD); the Kidney Disease: Improving Global Outcomes (KDIGO) criterion 'certain drop in eGFR' and rapid kidney function decline [estimated glomerular filtration rate (eGFR) slope steeper than -3 mL/min/1.73 m2/year]. RESULTS: After exclusion of participants with an eGFR <60 mL/min/1.73 m2 at baseline and those with type 2 diabetes or impaired fasting glycaemia at any time during follow-up (remaining n = 2174), there was a 113% higher risk for a rapid decline in kidney function in participants with adiponectin above the third tertile (T3) versus below the first tertile (T1) (Ptrend = 0.004) and a 53% higher risk for kidney function decline as defined by the KDIGO criterion (Ptrend = 0.04). In a cross-sectional analysis, adiponectin was positively associated with urinary albumin:creatinine ratio at baseline (P = 0.009). CONCLUSIONS: In a healthy cohort from the general population, higher levels of plasma adiponectin were associated with decreased renal function at baseline and at follow-up. This result is similar to what is observed in people with diabetic nephropathy, in contrast with animal models of nephropathy.

Pain in women with knee and/or hip osteoarthritis is related to systemic inflammation and to adipose tissue dysfunction: Cross-sectional results of the KHOALA cohort.

BACKGROUND: Considering the role of metabolic diseases in osteoarthritis (OA), we investigated whether biomarkers of adipose tissue dysfunction could be associated with OA-related pain. DESIGN: We cross-sectionally analyzed patients with knee and/or hip OA at inclusion in the KHOALA cohort. We used visual analogic scale (VAS) for pain, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Osteoarthritis Knee and Hip Quality of Life (OAKHQOL) pain subscores. At inclusion, we measured ultra-sensitive CRP (usCRP), leptin and adiponectin for calculation of leptin:adiponectin ratio (LAR), a marker of adipose tissue dysfunction associated with central adiposity, high-molecular-weight adiponectin, visfatin and apolipoproteins. Univariate and multivariable analyses using stepwise linear regression models were performed to search for correlation between pain assessments and these biomarkers, with systematic adjustment on age. RESULTS: In 596 women with hip and/or knee OA, multivariable analyses indicated that higher pain intensity was associated with higher LAR (VAS pain: ß=0.49; p = 0.0001, OAKHQOL pain: ß=-0.46; p = 0.0002, WOMAC pain: ß=0.30; p = 0.001) in the whole group as well as in hip or knee OA patients considered separately. Pain intensity correlated also with usCRP level (VAS pain: ß= 0.27; p = 0.02, OAKHQOL pain: ß =-0.30; p = 0.01) and Kellgren-Lawrence score. In 267 men, no correlation between biomarkers and pain was found. CONCLUSION: Serum LAR and usCRP level are associated with pain level, independently of radiographic structural severity in women with hip and/or knee OA, emphasizing the role of adipose tissue dysfunction and of meta-inflammation in pain experience in the female population.

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.

[Improvement of the pre-examination phase of medical biology exams at the Henri Mondor University Hospitals: a pilot study]. / Une étude pilote pour l'amélioration de l'étape pré-analytique des examens de biologie médicale pris en charge au sein des hôpitaux universitaires Henri Mondor.

The medical and university department of biology pathology at Henri Mondor hospital in Créteil has been engaged in an NF EN ISO 15189 accreditation process since 2014. One of the elements of this process concerns the quality of handling of samples and their transportation to laboratories, including the implementation place requires fighting against pre-examination non-conformities, which are the source of many dysfunctions. The pre-examination group has implemented several actions in a targeted care service. Thanks to these, the rate of non-conformities has halved in 18 months. In parallel, a work project targeting student nurses on internship was born to follow up on the results of a statistical study carried out by the pre-examination group on non-conformities. The objective of the project was to include nursing students on internship in a full support course on good sampling practices and pre-analytical non-conformities. This was based on the realization of two knowledge quizzes (before and after training), theoretical training, and visits to several laboratories. This study lasted 10 months with the participation of 37 students. The results showed a marked improvement in knowledge of pre-analytics as well as total satisfaction of all students. Our approach has helped to better understand the needs of laboratories and demonstrates the usefulness of training students in good sampling practices in order to ensure better patient care as well as an improvement in their comfort and well-being.

Fat gain differs by sex and hormonal status in persons living with suppressed HIV switched to raltegravir/etravirine.

: Fat gain is reported in integrase strand transfer inhibitors exposed persons living with HIV. We investigated in 165 persons living with HIV (117 men/48 women), included in the 96-week ANRS-163-ETRAL trial and switched to raltegravir/etravirine, the impact of sex, menopausal status and ovarian reserve (detectable anti-Müllerian hormone). From baseline to 48/96 weeks, women with ovarian reserve were protected from raltegravir/etravirine-induced weight/fat gain and associated insulin-resistance while peri/postmenopausal women increased weight, fat and insulin resistance as did men. The functional ovarian status could protect against raltegravir/etravirine-induced weight gain.