Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir.

OBJECTIVES: Our aim was to compare the clinical and virological outcomes in Omicron BA.1- and BA.2-infected patients who received sotrovimab with those in patients who received nirmatrelvir for the prevention of severe COVID-19. METHODS: In this multi-centric, prospective ANRS 0003S CoCoPrev cohort study, patients at a high risk of progression of mild-to-moderate BA.1 or BA.2 COVID-19 who received sotrovimab or nirmatrelvir were included. The proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR conversion, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multi-variable Cox proportional hazard model was used to determine the time to negative PCR conversion and a mixed-effect model for the dynamics of viral decay. RESULTS: Amongst 255 included patients, 199 (80%) received ≥3 vaccine doses, 195 (76%) received sotrovimab, and 60 (24%) received nirmatrelvir. On day 28, new COVID-19-related hospitalization occurred in 4 of 193 (2%; 95% CI, 1-5%) sotrovimab-treated patients and 0 of 55 nirmatrelvir-treated patients (p 0.24). One out of the 55 nirmatrelvir-treated patients died (2%; 95% CI, 0-10%). The median time to negative PCR conversion was 11.5 days (95% CI, 10.5-13) in the sotrovimab-treated patients vs. 4 days (95% CI, 4-9) in the nirmatrelvir-treated patients (p < 0.001). Viral decay was faster in the patients who received nirmatrelvir (p < 0.001). In the multi-variable analysis, nirmatrelvir and nasopharyngeal PCR cycle threshold values were independently associated with faster conversion to negative PCR (hazard ratio, 2.35; 95% CI, 1.56-3.56; p < 0.0001 and hazard ratio, 1.05; 95% CI, 1.01-1.08; p 0.01, respectively). CONCLUSIONS: Early administration of nirmatrelvir in high-risk patients compared with that of sotrovimab was associated with faster viral clearance. This may participate to decrease transmission and prevent viral resistance.

Brief Report: Frailty in Aging People Living With HIV: A Matched Controlled Study.

BACKGROUND: We compared the prevalence of frailty among aging people living with HIV (PLHIV) with people without HIV from the ANS EP58 HAND 55-70 Study. METHODS: Cross-sectional multicentric study which consecutively included 200 PLHIV and 1000 people without HIV from the French national CONSTANCES cohort, matched on age, sex, and education level. PLHIV were aged 55-70 years, with a HIV viral load < 50 copies/mL and a lymphocyte T-CD4 level > 200 cells/µL for the last 24 and 12 months, respectively. We measured frailty (>2 items) and prefrailty (one or 2 items) using a proxy of the 5-item Fried score. Multivariate logistic regression was performed to assess the association between HIV and frailty/prefrailty, adjusting for demographic, social, behavioral, and comorbidity confounders. RESULTS: Outcome measures were available for 192 PLHIV and 822 people without HIV. The median age was 62 years, and 84.9% were men. Among PLHIV, the median CD4 cell count was 645.5 cells/µL. Prevalence of frailty/prefrailty was 5.73%/57.3% in PLHIV vs. 1.73%/52.2% in people without HIV, respectively. HIV was associated with prefrailty/frailty [odds ratio = 1.89; 95% confidence interval = 1.37 to 2.61), but after adjusting for social and behavioral factors and comorbidities, HIV was not significantly associated with prefrailty/frailty (odds ratio = 1.24; 95% confidence interval: = 0.84 to 1.81). In PLHIV only, frailty/prefrailty was associated with depressive symptomatology, kidney disease, and time since HIV infection. CONCLUSIONS: Prevalence of frailty is increased in aging PLHIV with well-controlled HIV disease, but other factors than HIV are predominant, particularly depression and comorbidities.

HIV-mediated immune aging in young adults infected perinatally or during childhood.

BACKGROUND: HIV-infected patients progressing towards disease present a premature immune aging profile, characterized by the exhaustion of lymphopoiesis. The development of these anomalies may be prevented in young HIV-infected patients owing to their robust immune resources and lymphocyte regeneration capacities. METHODS: An immunomonitoring substudy was designed for young adults aged between 18 and 25 years, living with HIV since childhood included in the national ANRS Co19 COVERTE Cohort. We compared markers associated with immune aging, including the frequency of circulating hematopoietic progenitors and the phenotype of lymphocyte populations, with those of patients infected with HIV in adulthood. RESULTS: HIV-infected young adults displayed decreasing numbers of CD34 hematopoietic progenitors and mature lymphocytes, indicative of general lymphopenia and reminiscent of the alterations found in patients infected in adulthood or uninfected elderly people. This highlights the strong impact of HIV on the immune system despite patient's young age at infection. Immune aging-related alterations were particularly obvious in young patients who presented high viral loads. CONCLUSION: HIV-infected young adults can present increased markers of immune activation and senescence, related to uncontrolled viral replication. This highlights the issue of noncompliance to antiretroviral therapy in patients at a young age, resulting in loss of viral control, premature immunosenescence, and potentially irreversible damage of their lymphopoietic system.

Metabolic risk factors in young adults infected with HIV since childhood compared with the general population.

AIM: Metabolic risk factors are poorly documented for the first generation of young adults who have lived with HIV since childhood. We compared their metabolic profile with that of adults of same age from the general population. METHODS: We conducted a cross-sectional analysis of data from two populations: (1) COVERTE (ANRS-CO19), a French national cohort of 18 to 30-year-old patients HIV-infected since childhood, and (2) ENNS, a national cross-sectional population-based household survey on nutrition. Body mass index (BMI), blood pressure, waist circumference, fasting glucose, triglycerides, and HDL-, LDL- and total cholesterol were measured in both studies. Direct standardization on overweight and education level and logistic regression were used to compare the prevalence of metabolic abnormalities between the two populations. RESULTS: Data from 268 patients from COVERTE and 245 subjects from ENNS were analyzed. Tobacco use was similar in both groups. HIV-infected patients had increased mean waist-to-hip ratio and triglycerides to HDL-cholesterol ratio and decreased mean HDL-cholesterol as compared to their counterparts from the general population in both genders. In HIV-infected patients, metabolic syndrome was identified in 13.2% of men (95% confidence interval [CI]: 7.1-19.2) and 10.4% (95% CI: 5.4-15.3) of women versus 10.6% (95%CI: 1.5-19.7) and 1.7% (95%CI: 0-4.1) in subjects from the general population, respectively. CONCLUSION: Young adults infected with HIV since childhood had a higher prevalence of dyslipidemia and metabolically detrimental fat distribution than adults of same age of the general population, supporting close monitoring for cardiometabolic diseases.

Nutrient patterns and their food sources in an International Study Setting: report from the EPIC study.

BACKGROUND: Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. METHODOLOGY/PRINCIPAL FINDINGS: We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. CONCLUSION/SIGNIFICANCE: The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level.

Consumption of dairy products and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Prospective studies have consistently reported lower colorectal cancer risks associated with higher intakes of total dairy products, total milk and dietary calcium. However, less is known about whether the inverse associations vary for individual dairy products with differing fat contents. MATERIALS AND METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between intakes of total milk and milk subtypes (whole-fat, semi-skimmed and skimmed), yoghurt, cheese, and dietary calcium with colorectal cancer risk amongst 477,122 men and women. Dietary questionnaires were administered at baseline. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for relevant confounding variables. RESULTS: During the mean 11 years of follow-up, 4,513 incident cases of colorectal cancer occurred. After multivariable adjustments, total milk consumption was inversely associated with colorectal cancer risk (HR per 200 g/day 0.93, 95% CI: 0.89-0.98). Similar inverse associations were observed for whole-fat (HR per 200 g/day 0.90, 95% CI: 0.82-0.99) and skimmed milk (HR per 200 g/day 0.90, 95% CI: 0.79-1.02) in the multivariable models. Inverse associations were observed for cheese and yoghurt in the categorical models; although in the linear models, these associations were non-significant. Dietary calcium was inversely associated with colorectal cancer risk (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99); this association was limited to dairy sources of calcium only (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99), with no association observed for non-dairy calcium sources (HR per 200 mg/day 1.00, 95% CI: 0.81-1.24). CONCLUSIONS: Our results strengthen the evidence for a possible protective role of dairy products on colorectal cancer risk. The inverse associations we observed did not differ by the fat content of the dairy products considered.

Fruit and vegetable consumption and mortality: European prospective investigation into cancer and nutrition.

In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.

Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. RESULTS: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. CONCLUSIONS: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

Challenges in estimating the validity of dietary acrylamide measurements.

BACKGROUND: Acrylamide is a chemical compound present in tobacco smoke and food, classified as a probable human carcinogen and a known human neurotoxin. Acrylamide is formed in foods, typically carbohydrate-rich and protein-poor plant foods, during high-temperature cooking or other thermal processing. The objectives of this study were to compare dietary estimates of acrylamide from questionnaires (DQ) and 24-h recalls (R) with levels of acrylamide adduct (AA) in haemoglobin. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC) study, acrylamide exposure was assessed in 510 participants from 9 European countries, randomly selected and stratified by age, sex, with equal numbers of never and current smokers. After adjusting for country, alcohol intake, smoking status, number of cigarettes and energy intake, correlation coefficients between various acrylamide measurements were computed, both at the individual and at the aggregate (centre) level. RESULTS: Individual level correlation coefficient between DQ and R measurements (r DQ,R) was 0.17, while r DQ,AA and r R,AA were 0.08 and 0.06, respectively. In never smokers, r DQ,R, r DQ,AA and r R,AA were 0.19, 0.09 and 0.02, respectively. The correlation coefficients between means of DQ, R and AA measurements at the centre level were larger (r > 0.4). CONCLUSIONS: These findings suggest that estimates of total acrylamide intake based on self-reported diet correlate weakly with biomarker AA Hb levels. Possible explanations are the lack of AA levels to capture dietary acrylamide due to individual differences in the absorption and metabolism of acrylamide, and/or measurement errors in acrylamide from self-reported dietary assessments, thus limiting the possibility to validate acrylamide DQ measurements.

Dietary acrylamide intake of adults in the European Prospective Investigation into Cancer and Nutrition differs greatly according to geographical region.

PURPOSE: Methodological differences in assessing dietary acrylamide (AA) often hamper comparisons of intake across populations. Our aim was to describe the mean dietary AA intake in 27 centers of 10 European countries according to selected lifestyle characteristics and its contributing food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: In this cross-sectional analysis, 36 994 men and women, aged 35-74 years completed a single, standardized 24-hour dietary recall using EPIC-Soft. Food consumption data were matched to a harmonized AA database. Intake was computed by gender and center, and across categories of habitual alcohol consumption, smoking status, physical activity, education, and body mass index (BMI). Adjustment was made for participants' age, height, weight, and energy intake using linear regression models. RESULTS: Adjusted mean AA intake across centers ranged from 13 to 47 µg/day in men and from 12 to 39 µg/day in women; intakes were higher in northern European centers. In most centers, intake in women was significantly higher among alcohol drinkers compared with abstainers. There were no associations between AA intake and physical activity, BMI, or education. At least 50 % of AA intake across centers came from two food groups "bread, crisp bread, rusks" and "coffee." The third main contributing food group was "potatoes". CONCLUSIONS: Dietary AA intake differs greatly among European adults residing in different geographical regions. This observed heterogeneity in AA intake deserves consideration in the design and interpretation of population-based studies of dietary AA intake and health outcomes.