Chemsex in HIV pre-exposure prophylaxis users: Assessment of mood disorders and addictive behavior.

The assessment of mood disorders and addiction linked to the practice of chemsex is of interest given the psychoactive substances used. The aim of this study was to assess risky sexual and addictive behavior to chemsex and related anxiety/depression symptoms in individuals receiving HIV pre-exposure prophylaxis (PrEP). In this cross-sectional study, all adults presenting for PrEP renewal at French sexual health centers were enrolled from January 2018 to March 2019. Participants completed a questionnaire on chemsex (i.e., the use of psychoactive substances before/during sex), including adapted Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to chemsex addiction (questions of ASSIST were modified to focus on chemsex). Anxiety/depression was assessed with the Hospital Anxiety and Depression Scale. In the last 3 months before enrollment, 39.8% (94/236) of participants reported chemsex. The main psychoactive substances consumed during chemsex were cathinones (74.6%), gamma-hydroxybutyrate (66.3%), and other psychostimulants (60%). The median score of the chemsex-focused ASSIST was 8 [IQR25-75 : 3-15]; 72.2% of participants had a score justifying at least a brief intervention (>4). In multivariate analyses, anxiety and cathinones consumption were associated with an ASSIST score >4: OR 13.65 (95% CI 1.68-662.7), P = 0.0062, and OR 8.468 (95% CI 2.066-43.059), P = 0.0014, respectively. The level of addiction to the practice of chemsex can be difficult to estimate for the user, and the ASSIST makes it possible to evaluate this addiction and to direct the subjects toward specialized consultations of addictology, sexual health, or PrEP renewals. The implementation of the modified ASSIST in these consultations can allow early systematic screening and counseling.

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers.

INTRODUCTION: Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. METHODS: We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. RESULTS: The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. DISCUSSION: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

Genome-wide Association Study and Meta-analysis on Alcohol-Associated Liver Cirrhosis Identifies Genetic Risk Factors.

BACKGROUND AND AIMS: Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. APPROACH AND RESULTS: We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10-17 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10-10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10-8 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. CONCLUSIONS: Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

Psychoactive substances, alcohol and tobacco consumption in HIV-infected outpatients.

OBJECTIVES: To assess the alcohol consumption, tobacco addiction and psychoactive substance use (PSU) of people living with HIV (PLHIV). DESIGN: Cross-sectional study in an HIV outpatient unit. METHODS: Autoquestionnaire systematically proposed to all patients during their usual clinical care visit during a 6-months period, for alcohol (AUDIT test), tobacco (Short Fagerstrom Test) and PSU (ASSIST V3.0 test). RESULTS: Of 1334 distributed questionnaires, 1018 PLHIV responded: 76.8% were men [528 patients were MSM), and the median age was 49 years (interquartile range: 42-46). A prevalence of excessive alcohol drinking was found in 22% [95% confidence interval (CI) 19.5-24.7%] and 44.6% (CI 41.5-47.7%) were current smokers, with high dependence in 29.1% (CI 24.9-33.7%). The prevalence of PSU was 37.8% (CI 34.8-41%) in the past 3 months: cannabis 27.7%, poppers 16.4%, cocaine 8.9%, psychotropic medications 7.1%, gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL) 4.7%, stimulants 3.1%, synthetic cathinones 2.7%, hallucinogens 1.5%. In the past 3 months, PSU was more prevalent in MSM than in non-MSM patients (46 versus 30%, P < 0.001). MSM consumed significantly more inhaled solvents (poppers) 31.0 versus 1.1%, GHB/GBL 7.8 versus 0.8%, stimulants 5.0 versus 1.1%, synthetic cathinones 4.9 versus 0.3%, and hallucinogens 2.3 versus 0.5%. CONCLUSION: Given the high prevalence of PSU and other addictions (alcohol and smoking) among PLHIV, and particularly among MSM, a systematic screening of PSU and other addictions should be part of routine clinical care.

Evaluation of laboratory tests for cirrhosis and for alcohol use, in the context of alcoholic cirrhosis.

Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests' ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with areas under the ROC curve (AUCs) of 0.91 ± 0.01 and 0.88 ± 0.01, respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88 ± 0.01 for INR and 0.85 ± 0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85 units/L gave 90% specificity and 37% sensitivity. For GGT, cut-off limits of 288 units/L in men and 138 units/L in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used.

[Contribution of therapeutic patient education to addiction medicine]. / Ce que l’éducation thérapeutique peut apporter à l’addictologie.

TPE can improve the efficacy of addiction medicine, for the benefit of patients and staff. It can help the patient withdraw from addiction, or at least achieve a better quality of life with this chronic condition..

Should HIV-infected patients be screened for silent myocardial ischaemia using gated myocardial perfusion SPECT?

PURPOSE: A higher prevalence of cardiovascular risk factors (CRFs) in HIV-infected patients, together with chronic infection and treatments, has resulted in an increased risk of silent myocardial ischaemia (SMI). The objective of this study was to evaluate whether myocardial SPECT should be used for screening HIV-infected patients with no clinical symptoms of coronary artery disease. METHODS: The prevalence of SMI detected by myocardial SPECT was determined in 94 HIV-infected patients with a normal clinical cardiovascular examination in relation to anthropomorphic parameters, CRFs, inflammatory and HIV infection status, and treatment. RESULTS: Coronary artery disease was detected in nine patients (eight with ischaemia, one with myocardial infarction), corresponding to 9.6 % positivity. All but two of the scintigraphic diagnoses of ischaemia were confirmed by coronarography. Univariate analysis revealed that the overall number of CRFs and the combination of gender and age were associated with a diagnosis of SMI (p < 0.05). According to multivariate analysis, the only independent parameter significantly associated with the scintigraphic diagnosis of SMI was the combination of gender and age (p = 0.01). All the positive myocardial SPECT scans were in men older than 52 years with at least two other CRFs. In this subpopulation of 47 patients, the prevalence of SMI detected by myocardial SPECT reached 19.2 %. CONCLUSION: In male HIV-infected patients older than 52 years and with at least two other CRFs, screening for SMI using myocardial SPECT was about four times more likely to be positive than in the general population. This may motivate physicians to advise these patients to undergo more systematic screening for SMI using this technique.

Suppression of HIV-1 replication by microRNA effectors.

The rate of HIV-1 gene expression is a key step that determines the kinetics of virus spread and AIDS progression. Viral entry and gene expression were described to be the key determinants for cell permissiveness to HIV. Recent reports highlighted the involvement of miRNA in regulating HIV-1 replication post-transcriptionally. In this study we explored the role of cellular factors required for miRNA-mediated mRNA translational inhibition in regulating HIV-1 gene expression. Here we show that HIV-1 mRNAs associate and co-localize with components of the RNA Induced Silencing Complex (RISC), and we characterize some of the proteins required for miRNA-mediated silencing (miRNA effectors). RCK/p54, GW182, LSm-1 and XRN1 negatively regulate HIV-1 gene expression by preventing viral mRNA association with polysomes. Interestingly, knockdown of RCK/p54 or DGCR8 resulted in virus reactivation in PBMCs isolated from HIV infected patients treated with suppressive HAART.