Perrine Roux

Retention in opioid substitution treatment: a major predictor of long-term virological success for HIV-infected injection drug users receiving antiretroviral treatment.

BACKGROUND The positive impact of opioid substitution treatment (OST) on opioid-dependent individuals with human immunodeficiency virus (HIV) infection is well documented, especially with regard to adherence to highly active antiretroviral therapy (HAART). We used the data from a 5-year longitudinal study of the MANIF 2000 cohort of individuals infected with HIV (as a result of injection drug use) and receiving HAART to investigate the predictors of long-term virological success. Design. Data were collected every 6 months from outpatient hospital services delivering HIV care in France. We selected all patients who were receiving HAART for at least 6 months (baseline visit) and who had indications for OST (ie, still dependent on opioids). We selected a total of 113 patients, accounting for a total of 562 visits for all the analyses. METHODS Long-term virological success was defined as an undetectable viral load after at least 6 months on HAART. Retention in OST was defined as the time interval between the last initiation or reinitiation of OST during HAART follow-up and any given visit on OST. A mixed logistic model was used to identify predictors of long-term virological success. RESULTS At baseline, 53 patients were receiving buprenorphine, 28 patients were receiving methadone, and 32 patients were not on OST. The median duration of OST was 25 months (range, 3-42 months). In the multivariate analysis, after adjustment for significant predictors of long-term virological success such as adherence to HAART and early virological response, retention in OST was associated with long-term virological success (odds ratio, 1.20 per 6-month increase; 95% confidence interval, 1.09-1.32). CONCLUSIONS Our study presents important evidence of the positive impact of retention in OST on HIV outcomes. Increasing access to OST based on a comprehensive model of care for HIV-infected patients who have indications for OST may foster adherence and ensure long-term response to HAART.

Acute and Long-Term Effects of Cannabis Use: A Review

Cannabis remains the most commonly used and trafficked illicit drug in the world. Its use is largely concentrated among young people (15- to 34-year-olds). There is a variety of cannabis use patterns, ranging from experimental use to dependent use. Men are more likely than women to report both early initiation and frequent use of cannabis. Due to the high prevalence of cannabis use, the impact of cannabis on public health may be significant. A range of acute and chronic health problems associated with cannabis use has been identified. Cannabis can frequently have negative effects in its users, which may be amplified by certain demographic and/or psychosocial factors. Acute adverse effects include hyperemesis syndrome, impaired coordination and performance, anxiety, suicidal ideations/tendencies, and psychotic symptoms. Acute cannabis consumption is also associated with an increased risk of motor vehicle crashes, especially fatal collisions. Evidence indicates that frequent and prolonged use of cannabis can be detrimental to both mental and physical health. Chronic effects of cannabis use include mood disorders, exacerbation of psychotic disorders in vulnerable people, cannabis use disorders, withdrawal syndrome, neurocognitive impairments, cardiovascular and respiratory and other diseases.

Effects of acute oral naltrexone on the subjective and physiological effects of oral D-amphetamine and smoked cocaine in cocaine abusers.

Despite the prevalent worldwide abuse of stimulants, such as amphetamines and cocaine, no medications are currently approved for treating this serious public health problem. Both preclinical and clinical studies suggest that the opioid antagonist naltrexone (NTX) is effective in reducing the abuse liability of amphetamine, raising the question of whether similar positive findings would be obtained for cocaine. The purpose of this study was to evaluate the ability of oral NTX to alter the cardiovascular and subjective effects of D-amphetamine (D-AMPH) and cocaine (COC). Non-treatment-seeking COC users (N=12) completed this 3-week inpatient, randomized, crossover study. Participants received 0, 12.5, or 50 mg oral NTX 60 min before active or placebo stimulant administration during 10 separate laboratory sessions. Oral AMPH (0, 10, and 20 mg; or all placebo) was administered in ascending order within a laboratory session using a 60-min interdose interval. Smoked COC (0, 12.5, 25, and 50 mg; or all placebo) was administered in ascending order within a laboratory session using a 14-min interdose interval. Active COC and AMPH produced dose-related increases in cardiovascular function that were of comparable magnitude. In contrast, COC, but not AMPH, produced dose-related increases in several subjective measures of positive drug effect (eg, high, liking, and willingness to pay for the drug). NTX did not alter the cardiovascular effects of AMPH or COC. NTX also did not alter positive subjective ratings after COC administration, but it did significantly reduce ratings of craving for COC and tobacco during COC sessions. These results show that (1) oral AMPH produces minimal abuse-related subjective responses in COC smokers, and (2) NTX reduces craving for COC and tobacco during COC sessions. Future studies should continue to evaluate NTX as a potential anti-craving medication for COC dependence.

Adherence to antiretroviral treatment in HIV-positive patients in the Cameroon context: promoting the use of medication reminder methods.

Objectives: Antiretroviral treatment (ART) scale-up in sub-Saharan Africa has made it possible to investigate the maintenance of adherence to HIV medications. We describe here adherence to ART and identify its correlates in the Cameroonian context. Design: Prospective cohort study in 9 rural district hospitals. Methods: A mixed logistic regression model was used to identify factors associated with adherence to ART in 401 patients with data prospectively collected on adherence. Results: Although 73% of patients were adherent after the first month on ART, this proportion decreased to 61% after 24 months. After adjustment for known factors of adherence to ART (such as knowledge, motivation and side-effects), patients who reported willingness to start ART before initiation, those who were satisfied with information provided by their physicians, and those who implemented reminder methods for ART intake {eg, using an alarm clock, mobile phone, or watch [odds ratio (95% confidence interval)] = 2.45 (1.58 to 3.79), but also the help of a relative to remind them or other methods} were more likely to be adherent to ART. Conclusions: Besides highlighting some correlates already known to have an impact on adherence to ART, our findings also underline the need to reinforce the counseling component of follow-up through innovative methods. Accordingly, training and implementation research should encourage the use of medication reminder methods, such as mobile phones, to assure adherence over time and improve long-term response to ART.

Buprenorphine/naloxone as a promising therapeutic option for opioid abusing patients with chronic pain: reduction of pain, opioid withdrawal symptoms, and abuse liability of oral oxycodone.

&NA; In opioid‐dependent individuals with chronic pain, buprenorphine/naloxone may be an effective therapeutic option using adequate dose and paying attention to withdrawal symptoms and pain. &NA; Few studies have examined abuse of prescription opioids among individuals with chronic pain under buprenorphine/naloxone (Bup/Nx) maintenance. The current 7‐week inpatient study assessed oral oxycodone self‐administration by patients with chronic pain who had a history of opioid abuse. Participants (n = 25) were transitioned from their preadmission prescribed opioid to Bup/Nx. All of the participants were tested under each of the sublingual Bup/Nx maintenance doses (2/0.5, 8/2 or 16/4 mg) in random order. During each maintenance period, participants could self‐administer oxycodone orally (0, 10, 20, 40 or 60 mg prescription opioids) or receive money during laboratory sessions. Drug choice (percentage) was the primary dependent variable. Subjective ratings of clinical pain and withdrawal symptoms also were measured. Mann‐Whitney tests compared percentage of drug choice for each active oxycodone dose to placebo. Logistic regression analyses identified correlates of oxycodone preference, defined as 60% or greater choice of oxycodone compared to money. Pain was significantly reduced while participants were maintained on Bup/Nx compared to preadmission ratings. No differences in percentage drug choice were observed between the active oxycodone doses and placebo under each Bup/Nx maintenance dose. However, factors associated with oxycodone preference were lower Bup/Nx maintenance dose, more withdrawal symptoms and more pain. These data suggest that Bup/Nx was effective in reducing pain and supplemental oxycodone use. Importantly, adequate management of pain and withdrawal symptoms by Bup/Nx may reduce oxycodone preference in this population.

Harmful alcohol consumption and patterns of substance use in HIV-infected patients receiving antiretrovirals (ANRS-EN12-VESPA Study): relevance for clinical management and intervention

Abstract Alcohol abuse affects secondary prevention and disease progression in HIV-infected patients, and adherence and response to treatment in those chronically treated. The objective of this study was to estimate the prevalence of harmful alcohol consumption (HAC) using various indicators and identify which groups of patients may require specific targeted interventions for HAC risk reduction. A cross-sectional survey, based on a random sample representative of people living with HIV/AIDS (PLWHA) was carried out in 102 French hospital departments delivering HIV care. As alcohol abuse is particularly detrimental to patients receiving highly active antiretroviral therapy (HAART), we focused only on those individuals receiving HAART with complete alcohol assessment (CAGE, AUDIT-C, regular binge drinking, N=2340). Collected information included medical and socio-demographic data, HIV risk behaviors, adherence to treatment and substance and alcohol use, together with depression, anxiety, and experience of attempted suicide or sex work. HAC prevalence was evaluated as follows: 12% (CAGE score ≥2), 27% (AUDIT-C), and 9% (regular binge drinking). Three groups were at higher risk of HAC: men who have sex with men using stimulants, polydrug users, and to a lesser degree, ex-drug users. Innovative intervention strategies to reduce HAC and improve HIV prevention and HAART adherence in various PLWHA populations need urgent testing and implementation. Such interventions for alcohol risk reduction remain central to promoting improved HIV prevention and assuring HAART effectiveness in these populations.

Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville)

Objective Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC. Methods In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively. Results In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively). Conclusions Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence. Trial registration Number Eudract 2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511

Determinants of the underreporting of alcohol consumption by HIV/HCV co-infected patients during face-to-face medical interviews: the role of the physician.

OBJECTIVES The objective of this study was to assess to what extent HIV/HCV co-infected patients underreport alcohol use to their physician with respect to self-reports from self-administered questionnaires (SAQ) and identify correlates of alcohol underreporting during face-to-face medical interviews (FMI). DESIGN ANRS-CO13-HEPAVIH is a French multi-center cohort of HIV/HCV co-infected patients. METHODS Data were collected at enrolment using both SAQ and FMI while clinical data were retrieved from medical records. Alcohol consumption was assessed through SAQ and compared with FMI patient reports. Correlates of underreporting alcohol consumption during FMI with respect to SAQ were identified using logistic regression analysis. RESULTS Among 544 patients, 37% were classified as alcohol abusers according to AUDIT-C in the SAQ. During FMI, 14% underreported alcohol consumption. The following correlates were independently associated with underreporting alcohol consumption in FMI: not receiving HIV treatment, being followed up by a hepatologist for HCV infection and reporting a history of injecting drug use. CONCLUSIONS These results highlight the difficulties in alcohol consumption assessment which HCV specialists may face when suggesting to their HIV/HCV co-infected patients that they cease drinking completely. Patient awareness about the real need to reduce their alcohol use before starting HCV therapy may also contribute to underreporting. Innovative strategies for alcohol risk-reduction, including the promotion of controlled consumption and access to multidisciplinary teams, should be implemented for HIV/HCV co-infected patients in order to reduce barriers to HCV treatment.

Reducing harm from injecting pharmaceutical tablet or capsule material by injecting drug users.

BACKGROUND It has long been known that drug users may use a variety of pharmaceutical preparations by injection, many of which are not intended for intravenous administration (e.g. buprenorphine, methylphenidate, oxycodone). The introduction of tablet fillers such as talc or starch, in the blood circulation may cause, besides local injection site complications, pulmonary emboli. To reduce the harmful consequences of injecting such solutions, drug users have been encouraged to use filters. This research studied the effectiveness of an injection drug user syringe filter (IDUSF) in eliminating these particles. METHODS Generic buprenorphine and methylphenidate (Ritaline®), both containing talc, are frequently diverted for use by injection in France. The aim of our laboratory-based study was to compare the effectiveness of an IDUSF (Sterifilt®, filter pore size = 10 µm) versus no filtration, at reducing the number of particles in solutions of dissolved generic buprenorphine and Ritaline®. RESULTS Compared with a non-filtered solution drawn up through a 30G needle, filtering of the generic buprenorphine solution eliminated approximately 85% of all particles between 1 and 5 µm in diameter and 97% of particles between 5 and 18 µm. In the Ritaline® solution, these values were two-thirds and 95%, respectively. CONCLUSION Preliminary results indicate that IDUSF are effective in significantly filtering out large particles, which are responsible for major harms like pulmonary emboli. One strategy for alleviating these consequences is to promote the implementation of IDUSF in harm reduction programs, accompanied by training of social workers, peers and drug users.

Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: Results from the ANRS CO13 HEPAVIH cohort study

BACKGROUND & AIMS We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. METHODS Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (≥3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. RESULTS After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p=0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST; p=0.002 for ALT). CONCLUSIONS Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury.