Visual interpretation of brain hypometabolism related to neurological long COVID: a French multicentric experience.

BACKGROUND: This multicentre study aimed to provide a qualitative and consensual description of brain hypometabolism observed through the visual analysis of 18F-FDG PET images of patients with suspected neurological long COVID, regarding the previously reported long-COVID hypometabolic pattern involving hypometabolism in the olfactory bulbs and other limbic/paralimbic regions, as well as in the brainstem and cerebellum. METHODS: From the beginning of August 2021 to the end of October 2021, the brain 18F-FDG PET scans of patients referred for suspected neurological long COVID with positive reverse transcription polymerase chain reaction (RT-PCR) and/or serology tests for SARS-CoV-2 infection were retrospectively reviewed in three French nuclear medicine departments (143 patients; 47.4 years old ± 13.6; 98 women). Experienced nuclear physicians from each department classified brain 18F-FDG PET scans according to the same visual interpretation analysis as being normal, mildly to moderately (or incompletely) affected, or otherwise severely affected within the previously reported long-COVID hypometabolic pattern. RESULTS: On the 143 brain 18F-FDG PET scans performed during this 3-month period, 53% of the scans were visually interpreted as normal, 21% as mildly to moderately or incompletely affected, and 26% as severely affected according to the COVID hypometabolic pattern. On average, PET scans were performed at 10.9 months from symptom onset (± 4.8). Importantly, this specific hypometabolic pattern was similarly identified in the three nuclear medicine departments. Typical illustrative examples are provided to help nuclear physicians interpret long-COVID profiles. CONCLUSION: The proposed PET metabolic pattern is easily identified upon visual interpretation in clinical routine for approximately one half of patients with suspected neurological long COVID, requiring special consideration for frontobasal paramedian regions, the brainstem and the cerebellum, and certainly further adapted follow-up and medical care, while the second half of patients have normal brain PET metabolism on average 10.9 months from symptom onset.

HCV cure: an appropriate moment to reduce cannabis use in people living with HIV? (ANRS CO13 HEPAVIH data).

BACKGROUND: Thanks to direct-acting antivirals, hepatitis C virus (HCV) infection can be cured, with similar rates in HCV-infected and HIV-HCV co-infected patients. HCV cure is likely to foster behavioral changes in psychoactive substance use, which is highly prevalent in people living with HIV (PLWH). Cannabis is one substance that is very commonly used by PLWH, sometimes for therapeutic purposes. We aimed to identify correlates of cannabis use reduction following HCV cure in HIV-HCV co-infected cannabis users and to characterize persons who reduced their use. METHODS: We used data collected on HCV-cured cannabis users in a cross-sectional survey nested in the ANRS CO13 HEPAVIH cohort of HIV-HCV co-infected patients, to perform logistic regression, with post-HCV cure cannabis reduction as the outcome, and socio-behavioral characteristics as potential correlates. We also characterized the study sample by comparing post-cure substance use behaviors between those who reduced their cannabis use and those who did not. RESULTS: Among 140 HIV-infected cannabis users, 50 and 5 had reduced and increased their use, respectively, while 85 had not changed their use since HCV cure. Cannabis use reduction was significantly associated with tobacco use reduction, a decrease in fatigue level, paying more attention to one's dietary habits since HCV cure, and pre-HCV cure alcohol abstinence (p = 0.063 for alcohol use reduction). CONCLUSIONS: Among PLWH using cannabis, post-HCV cure cannabis reduction was associated with tobacco use reduction, improved well-being, and adoption of healthy behaviors. The management of addictive behaviors should therefore be encouraged during HCV treatment.

Elevated Fatty Liver Index as a Risk Factor for All-Cause Mortality in Human Immunodeficiency Virus-Hepatitis C Virus-Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study).

BACKGROUND AND AIMS: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV-coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on Aids and Viral Hepatitis CO13 HEPAVIH cohort (983 patients, 4,432 visits), we tested whether elevated FLI (≥60) was associated with all-cause mortality. APPROACH AND RESULTS: After multiple adjustment, individuals with FLI ≥ 60 had almost double the risk of all-cause mortality (adjusted hazard ratio [95% confidence interval], 1.91 [1.17-3.12], P = 0.009), independently of the following factors: HCV cure (0.21 [0.07-0.61], P = 0.004), advanced fibrosis (1.77 [1.00-3.14], P = 0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82-15.69], P < 10-3 ), history of indirect clinical signs of cirrhosis (2.80 [1.22-6.41], P = 0.015), and HIV Centers for Disease Control and Prevention clinical stage C (2.88 [1.74-4.79], P < 10-3 ). CONCLUSIONS: An elevated FLI (≥60) is a risk factor for all-cause mortality in HIV-HCV-coinfected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct-acting antivirals, these findings encourage the more systematic use of noninvasive steatosis biomarkers to help identify coinfected patients with higher mortality risk.

HCV Cure and Cannabis Abstinence Facilitate Tobacco Smoking Quit Attempts in HIV-HCV Co-Infected Patients (ANRS CO13 HEPAVIH Cohort Study).

In Western countries, tobacco smoking is highly prevalent among patients co-infected with HIV and hepatitis C virus (HCV). In the era of antiretrovirals and HCV cure, smoking-related health damages contribute greatly to morbidity and mortality in HIV-HCV co-infected patients. We used longitudinal data from the ANRS CO13 HEPAVIH cohort to identify the correlates of tobacco smoking quit attempts (TSQA) in HIV-HCV co-infected patients. TSQA were modelled using a multivariable discrete-time Cox proportional hazards model in 695 HIV-HCV co-infected tobacco smokers. HCV cure was associated with a 76% higher chance of TSQA (adjusted hazard ratio [95% confidence interval]: 1.76 [1.06-2.93], p = 0.029), and cannabis use with a 37% lower chance (0.63 [0.40-1.00], p = 0.049), independently of the mode of HIV transmission, other psychoactive substance use, and body mass index. Patients should be screened for tobacco and cannabis use at HCV treatment initiation and during follow-up. They should also be provided with comprehensive counselling and referral to addiction services. Non-smoking routes of cannabis administration should be promoted for cannabis users who wish to quit smoking tobacco.

Life after hepatitis C cure in HIV-infected people who inject drugs and men who have sex with men treated with direct-acting antivirals in France: Health perceptions and experiences from qualitative and quantitative findings (ANRS CO13 HEPAVIH).

There remains a substantial gap in our understandings of the life experiences of patients following HCV cure among HIV-HCV-co-infected people who inject drugs (PWID) and men who have sex with men (MSM), two key populations targeted for HCV elimination. We described the experiences and perspectives of HIV-positive PWID and MSM, HCV-cured following treatment with direct-acting antivirals (DAA). We used an exploratory sequential mixed approach using both qualitative data (semi-structured interviews with 27 PWID and 20 MSM) and quantitative data (self-administered questionnaires with 89 PWID) via the prospective ANRS CO13 HEPAVIH cohort. PWID reported improvements in physical health-related quality of life (HRQL) and self-reported symptoms following treatment, but no significant change in mental HRQL. During interviews, several MSM, more recently diagnosed with HCV, expressed less concern regarding HCV than HIV infection and interpreted improvements in their overall well-being after HCV cure to be more related to a closer connection with healthcare providers than with viral elimination. By contrast, PWID, particularly those previously exposed to interferon-based treatments, described major improvements in their physical HRQL. Both MSM and PWID reported improvements in cognitive or psychological wellbeing, and a majority of them reported some degree of concern over potential HCV reinfection. To conclude, though health benefits of HCV cure concern both groups, HIV-infected PWID and MSM may have different representations and experiences following DAA treatment, related to their history with HCV. They are thus likely to benefit from holistic, post-treatment follow-up care that is responsive to their evolving health and social contexts.

Human Immunodeficiency Virus/Hepatitis C Virus (HCV) Co-infected Patients With Cirrhosis Are No Longer at Higher Risk for Hepatocellular Carcinoma or End-Stage Liver Disease as Compared to HCV Mono-infected Patients.

It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child-Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine-Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow-up similar rates of HCV eradication than HCV mono-infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5-year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co-infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15-3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV-infected patients with cirrhosis, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions.

HCV-Related Mortality Among HIV/HCV Co-infected Patients: The Importance of Behaviors in the HCV Cure Era (ANRS CO13 HEPAVIH Cohort).

Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray's competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients. Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved. People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.

Prognostic factors of survival in HIV/HCV co-infected patients with hepatocellular carcinoma: The CARCINOVIC Cohort.

BACKGROUND & AIMS: HIV/HCV co-infected patients with hepatocellular carcinoma (HCC) have poorer survival than HCV mono-infected patients. We aimed to evaluate the prognostic factors for survival. METHODS: From 2006 to 2013, 55 incident HCCs among HIV+/HCV+ patients, from three ANRS cohorts, were compared with 181 HCCs in HIV-/HCV+ patients from the ANRS Cirvir cohort. RESULTS: HIV+/HCV+ patients were younger (50 years [IQR: 47-53] vs 62 [54-70], P < 0.001), male (89% vs 63%, P < 0.001) than HIV-/HCV+ patients. At HCC diagnosis, both groups had a majority of non-responders to anti-HCV-therapy, and HIV+/HCV+ patients had more frequently known a previous cirrhosis decompensation (31% vs 14%, P = 0.005). At diagnostic imaging, there were more infiltrative forms of HCC in HIV+/HCV+ group (24% vs 14%, P < 0.001), associated with tumour portal thrombosis in 29%. During a median follow-up period of 11.96 [5.51-27] months since HCC diagnosis, a majority of palliative treatments were decided in HIV+/HCV+ patients (51% vs 19%, P < 0.001). The 1 and 2-year crude survival rates were 61% versus 78% and 47% versus 63%, P = 0.003 respectively. In a Cox model multivariate analysis adjusted for the cohort, age and sex, the most important prognostic factor for survival was the infiltrative form of the tumour (aRR: 8.10 [4.17-15.75], P < 0.001). CONCLUSIONS: The radiological aggressiveness of the tumour is the best prognostic factor associated with poorer survival of HCC in HIV+/HCV+ patients. High α-foetoprotein level and decompensated cirrhosis are other ones. This justifies a particular attention to the detection and the management of small nodules in this high-risk population.

Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients.

BACKGROUND & AIMS: Coffee has anti-inflammatory and hepato-protective properties. In the general population, drinking ≥3cups of coffee/day has been associated with a 14% reduction in the risk of all-cause mortality. The aim of this study was to investigate the relationship between coffee consumption and the risk of all-cause mortality in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: ANRS CO13 HEPAVIH is an ongoing French nationwide prospective cohort of patients co-infected with HIV-HCV collecting both medical and psychosocial/behavioural data (annual self-administered questionnaires). We used a Cox proportional hazards model to estimate the effect of elevated coffee consumption (≥3cups/day) at baseline on all-cause mortality during the cohort's five-year follow-up. RESULTS: Over a median [interquartile range] follow-up of 5.0 [3.9-5.9] years, 77 deaths occurred among 1,028 eligible patients (mortality rate 1.64/100 person-years; 95% confidence interval [CI] 1.31-2.05). Leading causes of death were HCV-related diseases (n=33, 43%), cancers unrelated to AIDS/HCV (n=9, 12%), and AIDS (n=8, 10%). At the first available visit, 26.6% of patients reported elevated coffee consumption. Elevated coffee consumption at baseline was associated with a 50% reduced risk of all-cause mortality (hazard ratio 0.5; CI 0.3-0.9; p=0.032), after adjustment for gender and psychosocial, behavioral and clinical time-varying factors. CONCLUSIONS: Drinking three or more cups of coffee per day halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population. LAY SUMMARY: Coffee has anti-inflammatory and hepato-protective properties but its effect on mortality risk has never been investigated in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This study shows that elevated coffee consumption (≥3cups/day) halves all-cause mortality risk in patients co-infected with HIV-HCV. The benefits of coffee extracts and supplementing dietary intake with other anti-inflammatory compounds need to be evaluated in this population.

Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH).

BACKGROUND: Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients. METHODS: HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily). RESULTS: Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use. CONCLUSIONS: Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice.

Imaging Features and Prognosis of Hepatocellular Carcinoma in Patients with Cirrhosis Who Are Coinfected with Human Immunodeficiency Virus and Hepatitis C Virus.

PURPOSE: To evaluate the effect of human immunodeficiency virus (HIV) coinfection on hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with cirrhosis in terms of HCC morphologic subtypes and survival prognosis at the time of radiologic diagnosis. MATERIALS AND METHODS: The study was approved by the institutional review board and patients gave their written informed consent. Two databases, one for HIV-HCV patients and the other for HCV-infected patients without HIV infection, were obtained from prospective multicenter cohorts. Inclusion criteria were a confirmed diagnosis of cirrhosis and the discovery of HCC at imaging between January 2008 and December 2012. This study included 35 HIV-HCV patients with cirrhosis (32 men and three women; median age, 50 years [age range, 40-65 years]; Child-Pugh classification A, 21 patients; classification B, 10 patients; classification C, four patients) and 35 infected HCV patients with cirrhosis (29 men and six women; median age, 56 years [age range, 41-83 years]; Child-Pugh classification A, 26 patients; classification B, six patients; classification C, three patients) who were the control group. Computed tomographic or magnetic resonance images were analyzed for HCC subtypes, the number and size of nodules, and evidence of portal obstructing tumors. Fisher exact and Wilcoxon tests were used for comparisons and Kaplan-Meier plots were used for survival analysis. RESULTS: Infiltrative HCC was found in eight HIV-HCV patients with cirrhosis (23%) and in no HCV patients with cirrhosis (P = .002). All other HCCs were of a nodular type, with similar nodule sizes in the two groups. Portal-obstructing tumors were found in 10 HIV-HCV patients (eight of eight tumors were infiltrative and two of 27 tumors were nodular) but none were found in HCV patients (P = .001). Survival was dramatically shorter for HIV-HCV patients than for those with HCV, with a median of 17.2 months versus 54.7 months (P = .004). Survival time was dependent on the type of HCC, with probabilities of death at 12 months of 87% in infiltrative-type HCC, 32% in multiple-nodule type, and 5% in single-nodule type, which was found in both groups (log-rank test, P < .001). CONCLUSION: Unlike HCV-infected patients with cirrhosis, patients with cirrhosis coinfected with HIV and HCV frequently present at radiologic diagnosis with infiltrative-type HCC and portal-obstructing tumors, which results in dramatically shorter survival.

Use of first-generation HCV protease inhibitors in patients coinfected by HIV and HCV genotype 1.

BACKGROUND: In HCV genotype 1-infected patients with HIV co-infection, tritherapy [HCV protease inhibitors (PIs) plus peg-interferon and ribavirin] has been shown to have an increased rate of sustained virological response. However, complex drug-to-drug interactions and tolerability issues remain a concern. METHODS: Under the auspices of four French scientific societies of medicine, a committee was charged of establishing guidelines on the use of first-generation HCV PIs in these patients. This scientific committee based its work on preliminary results from tritherapy clinical trials in co-infected patients and, since data on these patients are still scarce, on the statements already made by the French Association for the Study of the Liver (AFEF) on the use of tritherapy in HCV mono-infected patients, written in May 2011 and updated in 2012. Each AFEF guideline concerning HCV monoinfection was examined to determine whether it could be used in the context of HIV/HCV coinfection. RESULTS: These guidelines are addressed for the treatment of coinfected patients with various profiles, including treatment-naïve or patients with failure to previous bitherapy and mention those patients for whom tritherapy should start or those for whom it should be delayed. Preliminary results of triple therapy as well as factors associated to virological response are also discussed. Other issues include virological monitoring, clinical and virological criteria to stop therapy, practical treatment management, treatment adherence and the management of side effects and interactions with antiretroviral drugs. These guidelines were submitted for critical review to independent experts.

Vaccine knowledge in students in Paris, France, and surrounding regions.

INTRODUCTION: In France, young adults are legally freed from parental authority at the age of 18 years and are, thus, responsible for their own vaccine record. This young adult population is more frequently exposed to vaccine-preventable infectious diseases. OBJECTIVE: To determine the factors associated with students' knowledge of the interval between two antitetanus boosters and their report of having up-to-date vaccinations. METHODS: In April 2009, a survey was conducted involving a random sample of students between 18 and 25 years of age eating lunch at university dining facilities in Paris and its suburbs (Ile de France). RESULTS: Among the 677 students approached, 583 agreed to participate. Only 207 (36%) of respondents knew the recommended dosing interval between two doses of tetanus vaccine booster (10 years). The majority of students (69%) reported having up-to-date vaccinations. Declaring having up-to-date vaccinations was significantly associated with having a general practitioner (OR 3.03 [95% CI 1.69 to 5.55]). Health care students were significantly more likely to know the decennial interval between two antitetanus boosters (OR 2 [95% CI 1.28 to 3.25]). Most of responding students (n=519 [89%]) believed that vaccines were very useful. CONCLUSIONS: An overall lack of knowledge of vaccines was observed among this student population. Health care providers, such as GPs and university medical practice staff, who interact with these young individuals have an essential role to promote better vaccination coverage in this population.

INTRODUCTION: En France, les jeunes adultes sont légalement libérés de l'autorité parentale à 18 ans et deviennent donc responsables de leur dossier de vaccination. La population de jeunes adultes est davantage exposée aux maladies infectieuses évitables par la vaccination. OBJECTIF: Déterminer les facteurs associés aux connaissances des étudiants sur l'intervalle entre les deux doses de rappel du vaccin contre le tétanos et sur leur déclaration d'avoir une couverture vaccinale. MÉTHODOLOGIE: En avril 2009, un sondage a été mené auprès d'un échantillon aléatoire d'étudiants de 18 à 25 ans qui, le midi, mangent aux cafétérias universitaires de Paris et des banlieues (Île de France). RÉSULTATS: Sur les 677 étudiants abordés, 583 ont accepté de participer. Seulement 207 des répondants (36 %) connaissaient l'intervalle recommandé entre deux doses de rappel du vaccin contre le tétanos (dix ans). La majorité des étudiants (69 %) déclarai avoir une couverture vaccinale à jour. Cette déclaration s'associait de manière significative au fait d'avoir un praticien général (RC 3,03 95 % IC 1,69 à 5,55]). Les étudiants du milieu de la santé étaient considérablement plus enclins à connaître l'intervalle de dix ans entre deux doses de rappel du vaccin antitétanique (RC 2 [95 % IC 1,28 à 3,25]). La plupart des étudiants répondants (n=519 [89 %]) croyaient en l'utilité des vaccins. CONCLUSIONS: Les chercheurs ont constaté une ignorance globale des vaccins au sein de cette population de patients. Les dispensateurs de soins, tels que les praticiens généraux et le personnel médical en milieu universitaire, qui dialoguent avec ces jeunes, ont un rôle essentiel à jouer pour promouvoir une meilleure couverture vaccinale au sein de cette population.