The International development of PROQOL-HCV: An instrument to assess the health-related quality of life of patients treated for Hepatitis C virus.

BACKGROUND: Hepatitis C virus (HCV) compromises Health-related Quality of Life (HRQL) with detriments to Physical, Mental and Social health domains. Treatment with interferon and ribavirin is associated with side effects which further impair HRQL. New treatments appear potent, effective and tolerable. However, Patient Reported Outcomes instruments that capture the impact on HRQL for people with hepatitis C are largely non-specific and will be needed in the new treatment era. Therefore, we developed a conceptually valid multidimensional model of HCV-specific quality of life and pilot survey instrument, the Patient Reported Outcome Quality of Life survey for HCV (PROQOL-HCV). METHODS: HCV patients from France (n = 30), Brazil (n = 20) and Australia (n = 20) were interviewed to investigate HCV-HRQL issues raised in the scientific literature and by treatment specialists. Interviews were recorded, transcribed and translated into English and French. RESULTS: Fifteen content dimensions were derived from the qualitative analysis, refined and fitted to four domains: (1) Physical Health included: fatigue, pain, sleep, sexual impairment and physical activity; (2) Mental Health: psychological distress, psychosocial impact, and cognition; (3) Social Health: support, stigma, social activity, substance use; (4) TREATMENT: management, side effects, and fear of treatment failure. The impact of some dimensions extended beyond their primary domain including: physical activity, cognition, sleep, sexual impairment, and the three treatment dimensions. A bank of 300 items was constructed to reflect patient reports and, following expert review, reduced to a 72-item pilot questionnaire. CONCLUSION: We present a conceptually valid multidimensional model of HCV-specific quality of life and the pilot survey instrument, PROQOL-HCV. The model is widely inclusive of the experience of hepatitis C and the first to include the treatment dimension.

Correlates of cocaine use during methadone treatment: implications for screening and clinical management (ANRS Methaville study).

BACKGROUND: Cocaine use is frequent in patients receiving methadone maintenance treatment (MMT) and can jeopardize their treatment response. Identifying clinical predictors of cocaine use during methadone treatment can potentially improve clinical management. We used longitudinal data from the ANRS Methaville trial both to describe self-reported occasional and regular cocaine use during MMT and to identify clinical predictors. METHODS: We selected 183 patients who had data on cocaine (or crack) use at months 0 (M0), M6, and/or M12, accounting for 483 visits. The outcome was "cocaine use" in three categories: "no," "occasional," and "regular" use. To identify factors associated with the outcome over time, we performed a mixed multinomial logistic regression. RESULTS: Time on methadone was significantly associated with a decrease in occasional but not in regular cocaine use from 14.7% at M0 to 7.1% at M12, and from 10.7% at baseline to 6.5% at M12, respectively. After multiple adjustments, opiate injection, individuals screening positive for attention deficit hyperactivity disorder (ADHD) symptoms, and those presenting depressive symptoms were more likely to regularly use cocaine. CONCLUSIONS: Although time on MMT had a positive impact on occasional cocaine use, it had no impact on regular cocaine use. Moreover, regular cocaine users were more likely to report opiate injection and to present ADHD and depressive symptoms. Early screening of these disorders and prompt tailored pharmacological and behavioral interventions can potentially reduce cocaine use and improve response to MMT. TRIAL REGISTRATION: The trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials, number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397 , and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

Suicidal risk among patients enrolled in methadone maintenance treatment: HCV status and implications for suicide prevention (ANRS Methaville).

BACKGROUND: Suicide is a critical issue among opioid users. The aim of this study was to assess the relationship between HCV status and suicidal risk in patients receiving methadone treatment. METHODS: We used data from Methaville, a multicenter, pragmatic randomized trial designed to evaluate the feasibility of methadone induction in primary care compared with induction in specialized centers. Suicidal risk was assessed at enrollment and after one year of methadone treatment using the suicidality module in the MINI International Neuropsychiatric Interview. Socio-demographic characteristics, drug and alcohol consumption, behavioral and personality factors, history of drug use and health indicators were also assessed. RESULTS: A total of 195 individuals were enrolled from January 2009 to December 2010. Suicidal risk assessment was available at month 0 (M0) and M12 for 159 (72%) and 118 (73%) individuals, respectively. Forty-four (28%) were at risk of suicide at M0 and 17 (14%) at M12 (p=0.004). One patient attempted suicide by overdose during the one-year follow-up. The following three factors were associated with suicidal risk: hepatitis C virus (HCV) positive status (OR [95%CI]=17.25 [1.14-161.07]; p=0.04), receiving food assistance (OR [95%CI]=0.05 [0.00-1.05]; p=0.05) and a higher number of health problems (OR [95%CI]=1.24 [1.08-1.44]; p=0.003). CONCLUSIONS: Special attention should be given to HCV-positive patients through suicidal risk prevention strategies and routine suicide assessment as part of a comprehensive approach to prevention and care for opioid users. Our results represent a new and powerful argument for the expansion of access to HCV treatment to drug users with chronic infection.

Insufficient access to harm reduction measures in prisons in 5 countries (PRIDE Europe): a shared European public health concern.

BACKGROUND: Prisoners constitute a high-risk population, particularly for infectious diseases. The aim of this study was to estimate the level of infectious risk in the prisons of five different European countries by measuring to what extent the prison system adheres to WHO/UNODC recommendations. METHODS: Following the methodology used in a previous French survey, a postal/electronic questionnaire was sent to all prisons in Austria, Belgium, Denmark and Italy to collect data on the availability of several recommended HIV-HCV prevention interventions and HBV vaccination for prisoners. A score was built to compare adherence to WHO/UNODC recommendations (considered a proxy of environmental infectious risk) in those 4 countries. It ranged from 0 (no adherence) to 12 (full adherence). A second score (0 to 9) was built to include data from a previous French survey, thereby creating a 5-country comparison. RESULTS: A majority of prisons answered in Austria (100 %), France (66 %) and Denmark (58 %), half in Belgium (50 %) and few in Italy (17 %), representing 100, 74, 89, 47 and 23 % coverage of the prison populations, respectively. Availability of prevention measures was low, with median adherence scores ranging from 3.5 to 4.5 at the national level. These results were confirmed when using the second score which included France in the inter-country comparison. Overall, the adherence score was inversely associated with prison overpopulation rates (p = 0.08). CONCLUSIONS: Using a score of adherence to WHO/UNODC recommendations, the estimated environmental infectious risk remains extremely high in the prisons of the 5 European countries assessed. Public health strategies should be adjusted to comply with the principle of equivalence of care and prevention with the general community.

Methadone induction in primary care (ANRS-Methaville): a phase III randomized intervention trial.

BACKGROUND: In France, the rapid scale-up of buprenorphine, an opioid maintenance treatment (OMT), in primary care for drug users has led to an impressive reduction in HIV prevalence among injecting drug users (IDU) but has had no major effect on Hepatitis C incidence. To date, patients willing to start methadone can only do so in a methadone clinic (a medical centre for drug and alcohol dependence (CSAPA) or a hospital setting) and are referred to primary care physicians after dose stabilization. This study aims to assess the effectiveness of methadone in patients who initiated treatment in primary care compared with those who initiated it in a CSAPA, by measuring abstinence from street opioid use after one year of treatment. METHODS/DESIGN: The ANRS-Methaville study is a randomized multicenter non-inferiority control trial comparing methadone induction (lasting approximately 2 weeks) in primary care and in CSAPA. The model of care chosen for methadone induction in primary care was based on study-specific pre-training of all physicians, exclusion criteria and daily supervision of methadone during the initiation phase. Between January 2009 and January 2011, 10 sites each having one CSAPA and several primary care physicians, were identified to recruit patients to be randomized into two groups, one starting methadone in primary care (n = 147), the other in CSAPA (n = 48). The primary outcome of the study is the proportion of participants abstinent from street opioids after 1 year of treatment i.e. non-inferiority of primary care model in terms of the proportion of patients not using street opioids compared with the proportion observed in those starting methadone in a CSAPA. DISCUSSION: The ANRS-Methaville study is the first in France to use an interventional trial to improve access to OMT for drug users. Once the non-inferiority results become available, the Ministry of Health and agency for the safety of health products may change the the New Drug Application (NDA) of methadone and make methadone induction by trained primary care physicians possible.The trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials.Number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397 and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

The burden of HIV experience and care among MSM having an HIV-positive seroconcordant steady partner: a possible research hypothesis. Results from the French VESPA ANRS EN-12 study.

OBJECTIVES: Prevention fatigue, relapse into unsafe sex practices and sexual behaviour changes have been reported in the community of men who have sex with men (MSM) since the introduction of highly active antiretroviral therapy. Engaging in a relationship with a seroconcordant partner is perceived by some HIV-positive MSM as an alternative prevention strategy to consistent condom use. This study addresses whether underlying clinical factors exist characterising HIV-positive MSM in seroconcordant stable partnerships, enrolled in the French national cross-sectional survey VESPA ANRS EN-12. METHODS: The study group comprised 322 HIV-positive MSM in stable relationships for more than 12 months, with a serodiscordant (n = 251) or seroconcordant (n = 71) steady partner. Clinical and psychosocial factors were analysed for HIV-positive MSM with a seroconcordant steady partner. RESULTS: Multiple adjustment by logistic regression showed that individuals with a seroconcordant steady partner were more likely to have a history of an AIDS-defining event (OR 95% CI 2.0 (1.1 to 3.7), p = 0.02) or be diagnosed as HIV positive before 1990 (OR 95% CI 2.2 (1.3 to 3.9), p = 0.004). Conversely, HIV-positive MSM experiencing virological success (ie, high treatment adherence and an undetectable viral load) were more likely to have a serodiscordant steady partner (OR 95% CI 0.5 (0.3 to 0.9), p = 0.02). CONCLUSIONS: Longitudinal studies are required to understand to what extent HIV history might influence partnership choices among HIV-positive MSM. Positive prevention programmes and reinforcement of treatment adherence strategies are needed for this population and their steady sexual partners.

Limited access to HIV prevention in French prisons (ANRS PRI2DE): implications for public health and drug policy.

BACKGROUND: Overpopulation, poor hygiene and disease prevention conditions in prisons are major structural determinants of increased infectious risk within prison settings but evidence-based national and WHO guidelines provide clear indications on how to reduce this risk. We sought to estimate the level of infectious risk by measuring how French prisons adhere to national and WHO guidelines. METHODS: A nationwide survey targeting the heads of medical (all French prisons) and psychiatric (26 French prisons) units was conducted using a postal questionnaire and a phone interview mainly focusing on access to prevention interventions, i.e. bleach, opioid substitution treatment (OST), HBV vaccination and post-exposure prophylaxis (PEP) for French prisoners. Two scores were built reflecting adherence to national and WHO international guidelines, ranging from 0 (no adherence) to 10 (maximum adherence) and 0 to 9 respectively. RESULTS: A majority (N=113 (66%)) of the 171 prisons answered the questionnaires, representing 74% coverage (46,786 prisoners) of the French prison population: 108 were medical units and 12 were psychiatric units. Inmate access to prevention was poor. The median[IQR] score measuring adherence to national guidelines was quite low (4.5[2.5; 5.5]) but adherence to WHO guidelines was even lower 2.5[1.5; 3.5]; PEP was absent despite reported risky practices. Unsuitable OST delivery practices were frequently observed. CONCLUSIONS: A wide gap exists between HIV prevention policies and their application in prisons. Similar assessments in other countries may be needed to guide a global policy reform in prison settings. Adequate funding together with innovative interventions able to remove structural and ideological barriers to HIV prevention are now needed to motivate those in charge of prison health, to improve their working environment and to relieve French prisoners from their currently debilitating conditions.

Non-medical use of opioids among HIV-infected opioid dependent individuals on opioid maintenance treatment: the need for a more comprehensive approach.

BACKGROUND: Opioid maintenance treatment (OMT) has a positive impact on substance use and health outcomes among HIV-infected opioid dependent patients. The present study investigates non-medical use of opioids by HIV-infected opioid-dependent individuals treated with buprenorphine or methadone. METHODS: The MANIF 2000 study is a longitudinal study that enrolled a cohort of 476 HIV-infected opioid-dependent individuals. Data were collected in outpatient hospital services delivering HIV care in France. The sample comprised all patients receiving OMT (either methadone or buprenorphine) who attended at least one follow-up visit with data on adherence to OMT (N = 235 patients, 1056 visits). Non-medical use of opioids during OMT was defined as having reported use of opioids in a non-medical context, and/or the misuse of the prescribed oral OMT by an inappropriate route of administration (injection or sniffing). After adjusting for the non-random assignment of OMT type, a model based on GEE was then used to identify predictors of non-medical use of opioids. RESULTS: Among the 235 patients, 144 (61.3%) and 91 (38.9%) patients were receiving buprenorphine and methadone, respectively, at baseline. Non-medical use of opioids was found in 41.6% of visits for 83% of individual patients. In the multivariate analysis, predictors of non-medical use of opioids were: cocaine, daily cannabis, and benzodiazepine use, experience of opioid withdrawal symptoms, and less time since OMT initiation. CONCLUSIONS: Non-medical use of opioids was found to be comparable in OMT patients receiving methadone or buprenorphine. The presence of opioid withdrawal symptoms was a determinant of non-medical use of opioids and may serve as a clinical indicator of inadequate dosage, medication, or type of follow-up. Sustainability and continuity of care with adequate monitoring of withdrawal symptoms and polydrug use may contribute to reduced harms from ongoing non-medical use of opioids.

Predictors of non-adherence to methadone maintenance treatment in opioid-dependent individuals: implications for clinicians.

BACKGROUND: Although methadone maintenance treatment (MMT) is recognized as the treatment of reference for opioid dependence, little information is available regarding the dynamic adherence to methadone and its determinants. With data from the Methaville trial we investigated the evolution of non-adherence to methadone and the effect of pre-treatment and in-treatment factors on longterm non-adherence to methadone. METHODS: We selected 145 patients to study adherence to methadone at 3, 6 and 12 months (M3, M6 and M12, respectively) using a multidimensional questionnaire and a 3-level variable "adherent"/"non adherent"/"highly nonadherent". We then identified the pre-treatment and in-treatment variables associated with long-term non-adherence to methadone at the M12 visit using a univariate logistic regression and two different multivariate models: the first incorporating only the pre-treatment variables, the second adding the in-treatment variables to the pre-treatment ones. RESULTS: At the M12 visit, 35.2% of the participants remained adherent, 55.9% and 9% were non-adherent and highly non-adherent, respectively. The multivariate analysis of long-term non-adherence to methadone showed 4 pre-treatment predictors and 1 in-treatment predictor as follows: being female, not having stable housing, alcohol consumption, cocaine use and perceiving methadone dose as inadequate. CONCLUSIONS: Our findings highlight that pretreatment predictors are important to consider when starting maintenance treatment for opioid dependence, such as cocaine use and problematic alcohol consumption but also low socio-economic levels. In addition, during maintenance treatment, in-treatment predictors such as methadone dose adequacy is a crucial issue to achieve good adherence to MMT.

Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions.

BACKGROUND: One important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices. METHODS: The ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis. RESULTS: HCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively). CONCLUSIONS: Identifying individuals at risk of HCV transmission during methadone treatment such as stimulant users, alcohol dependent individuals, and those at suicidal risk is necessary to optimize response to treatment. Innovative prevention approaches tailored to couples are also urgently needed and could decrease HCV-risk in this population. The trial is registered with the French Agency of Pharmaceutical Products (ANSM) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials. Number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397 and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

Impact of HIV comprehensive care and treatment on serostatus disclosure among Cameroonian patients in rural district hospitals.

This work aimed to analyze the rate of disclosure to relatives and friends over time and to identify factors affecting disclosure among seropositive adults initiating antiretroviral therapy (ART) in rural district hospitals in the context of decentralized, integrated HIV care and task-shifting to nurses in Cameroon. Stratall was a 24-month, randomized, open-label trial comparing the effectiveness of clinical monitoring alone with laboratory plus clinical monitoring on treatment outcomes. It enrolled 459 HIV-infected ART-naive adults in 9 rural district hospitals in Cameroon. Participants in both groups were sometimes visited by nurses instead of physicians. Patients with complete data both at enrolment (M0) and at least at one follow-up visit were included in the present analysis. A mixed Poisson regression was used to estimate predictors of the evolution of disclosure index over 24 months (M24).The study population included 385 patients, accounting for 1733 face-to-face interviews at follow-up visits from M0 to M24. The median [IQR] number of categories of relatives and friends to whom patients had disclosed was 2 [1]-[3] and 3 [2]-[5] at M0 and M24 (p-trend<0.001), respectively. After multiple adjustments, factors associated with disclosure to a higher number of categories of relatives and friends were as follows: having revealed one's status to one's main partner, time on ART, HIV diagnosis during hospitalization, knowledge on ART and positive ratio of follow-up nurse-led to physician-led visits measuring task-shifting. ART delivered in the context of decentralized, integrated HIV care including task-shifting was associated with increased HIV serological status disclosure.