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.

Distributive sharing among HIV-HCV co-infected injecting drug users: the preventive role of trust in one's physician.

This study, based on data from the MANIF 2000 cohort study, investigates the relationship between the lending of injecting equipment, drug use, and experience with HIV care. The sample comprised 224 HIV-HCV co-infected patients who reported having injected drugs in the previous six months and their 538 visits to clinical services. Longitudinal data were collected for medical status, and self-reported risk behaviors. A logistic regression GEE model was used to identify correlates of distributive sharing. After multiple adjustment, patients who reported trust in physicians were significantly less likely to report lending injection equipment while cocaine users were at increased risk. Promoting dialog between physicians and injecting drug users (IDUs) may play an important role in HIV-HCV positive prevention.

Treatment and care for injecting drug users with HIV infection: a review of barriers and ways forward.

We review evidence for effectiveness, cost-effectiveness, and coverage of antiretroviral therapy (ART) for injecting drug users (IDUs) infected with HIV, with particular attention to low-income and middle-income countries. In these countries, nearly half (47%) of all IDUs infected with HIV are in five nations--China, Vietnam, Russia, Ukraine, and Malaysia. In all five countries, IDU access to ART is disproportionately low, and systemic and structural obstacles restrict treatment access. IDUs are 67% of cumulative HIV cases in these countries, but only 25% of those receiving ART. Integration of ART with opioid substitution and tuberculosis treatment, increased peer engagement in treatment delivery, and reform of harmful policies--including police use of drug-user registries, detention of drug users in centres offering no evidence-based treatment, and imprisonment for possession of drugs for personal use--are needed to improve ART coverage of IDUs.

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

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 > or =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.

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.

Buprenorphine in primary care: risk factors for treatment injection and implications for clinical management.

AIMS: Though the introduction of office-based buprenorphine has greatly contributed to stem the HIV epidemic since 1995, concerns have been raised about the intravenous use of buprenorphine even in patients on substitution treatment. The aim of this study was to identify which factors are predictive of buprenorphine injection in patients receiving office-based buprenorphine. DESIGN AND SETTING: Subazur is a survey consisting of two longitudinal assessments of 111 stabilized patients receiving office-based buprenorphine in southeastern France. MEASUREMENTS: Patients were interviewed by phone at enrolment and 6 months later about social characteristics, addictive behaviors, treatment experiences, overdoses and suicide ideation or attempt. A logistic regression based on generalized estimating equations (GEE) was used to identify factors associated with buprenorphine injection at any interview. FINDINGS: Among the 111 patients (32% women, mean age 38 years), 36 reported buprenorphine injection after having started treatment initiation in 40 interviews. After adjustment for time since first injection, individuals perceiving their prescribed dosage as inadequate (OR=2.6 95%CI[1.2-5.7]) and those reporting a history of suicide ideation or attempt (OR=2.7 95%CI[1.1-7.0]) had approximately a three-fold higher risk of injecting buprenorphine. CONCLUSIONS: Providing adequate care for both drug dependence and psychiatric comorbidities in primary care is a major issue. Like heroin use during methadone treatment, buprenorphine injection should be regarded more as a response to inadequate care than simply as a "misuse". A re-assessment of the treatment efficacy through a possible dosage increase or a switch to methadone could potentially reduce diversion and assure sustained adherence to OST.

Harm reduction and equity of access to care for French prisoners: a review.

BACKGROUND: Despite France being regarded as a model of efficient harm reduction policy and equity of access to care in the general community, the health of French inmates is a critical issue, as harm reduction measures are either inaccessible or only partially implemented in French prisons. METHOD: Using specific inclusion and exclusion criteria, information was collected and analyzed about HIV, HBV and HCV prevalence, risk practices, mortality, access to harm reduction measures and care for French prison inmates. RESULTS: Data about the occurrence of bloodborne diseases, drug use and access to care in prisons remain limited and need urgent updating. Needle exchange programs are not yet available in French prisons and harm reduction interventions and access to OST remain limited or are heterogeneous across prisons. The continuity of care at prison entry and after release remains problematic and should be among the primary public health priorities for French prisoners. CONCLUSION: Preventive and harm reduction measures should be urgently introduced at least as pilot programs. The implementation of such measures, not yet available in French prisons, is not only a human right for prison inmates but can also provide important public health benefits for the general population.

Clinical Features and Complications of Coxiella burnetii Infections From the French National Reference Center for Q Fever.

Importance: Q fever remains widespread throughout the world; the disease is serious and causes outbreaks and deaths when complications are not detected. The diagnosis of Q fever requires the demonstration of the presence of Coxiella burnetii and the identification of an organic lesion. Objective: To describe the hitherto neglected clinical characteristics of Q fever and identifying risk factors for complications and death. Design, Setting, and Participants: This prospective cohort study conducted from January 1, 1991, through December 31, 2016, included patients treated at the French National Reference Center for Q fever with serologic findings positive for C burnetii and clinical data consistent with C burnetii infection. Clinical data were prospectively collected by telephone. Patients with unavailable clinical data or an unidentified infectious focus were excluded. Main Outcomes and Measures: Q fever complications and mortality. Results: Of the 180 483 patients undergoing testing, 2918 had positive findings for C burnetii and 2434 (68.8% men) presented with clinical data consistent with a C burnetii infection. Mean (SD) age was 51.8 (17.4) years, and the ratio of men to women was 2.2. At the time of inclusion, 1806 patients presented with acute Q fever, including 138 with acute Q fever that progressed to persistent C burnetii infection, and 766 had persistent focalized C burnetii infection. Rare and hitherto neglected foci of infections included lymphadenitis (97 [4.0%]), acute Q fever endocarditis (50 [2.1%]), hemophagocytic syndrome (9 [0.4%]), and alithiasic cholecystitis (11 [0.4%]). Vascular infection (hazard ratio [HR], 3.1; 95% CI, 1.7-5.7; P < .001) and endocarditis (HR, 2.4; 95% CI, 1.1-5.1; P = .02) were associated with an increased risk of death. Independent indicators of lymphoma were lymphadenitis (HR, 77.4; 95% CI, 21.2-281.8; P < .001) and hemophagocytic syndrome (HR, 19.1; 95% CI, 3.4-108.6; P < .001). The presence of anticardiolipin antibodies during acute Q fever has been associated with several complications, including hepatitis, cholecystitis, endocarditis, thrombosis, hemophagocytic syndrome, meningitis, and progression to persistent endocarditis. Conclusions and Relevance: Previously neglected foci of C burnetii infection include the lymphatic system (ie, bone marrow, lymphadenitis) with a risk of lymphoma. Cardiovascular infections were the main fatal complications, highlighting the importance of routine screening for valvular heart disease and vascular anomalies during acute Q fever. Routine screening for anticardiolopin antibodies during acute Q fever can help prevent complications. Positron emission tomographic scanning could be proposed for all patients with suspected persistent focused infection to rapidly diagnose vascular and lymphatic infections associated with death and lymphoma, respectively.

Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment.

BACKGROUND: The recording of outcomes from large-scale, simplified HAART (highly active antiretroviral therapy) programmes in sub-Saharan Africa is critical. We aimed to assess the effectiveness of such a programme held by Médecins Sans Frontières (MSF) in the Chiradzulu district, Malawi. METHODS: We scaled up and simplified HAART in this programme since August, 2002. We analysed survival indicators, CD4 count evolution, virological response, and adherence to treatment. We included adults who all started HAART 6 months or more before the analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed on a subsample of patients, and antiretroviral resistance mutations were analysed in plasma with viral loads greater than 1000 copies per mL. Analysis was by intention to treat. FINDINGS: Of the 1308 patients who were eligible, 827 (64%) were female, the median age was 34.9 years (IQR 29.9-41.0), and 1023 (78%) received d4T/3TC/NVP (stavudine, lamivudine, and nevirapine) as a fixed-dose combination. At baseline, 1266 individuals (97%) were HAART-naive, 357 (27%) were at WHO stage IV, 311 (33%) had a body-mass index of less than 18.5 kg/m2, and 208 (21%) had a CD4 count lower than 50 cells per muL. At follow-up (median 8.3 months, IQR 5.5-13.1), 967 (74%) were still on HAART, 243 (19%) had died, 91 (7%) were lost to follow-up, and seven (0.5%) discontinued treatment. Low body-mass index, WHO stage IV, male sex, and baseline CD4 count lower than 50 cells per muL were independent determinants of death in the first 6 months. At 12 months, the probability of individuals still in care was 0.76 (95% CI 0.73-0.78) and the median CD4 gain was 165 (IQR 67-259) cells per muL. In the cross-sectional survey (n=398), 334 (84%) had a viral load of less than 400 copies per mL. Of several indicators measuring adherence, self-reported poor adherence (<80%) in the past 4 days was the best predictor of detectable viral load (odds ratio 5.4, 95% CI 1.9-15.6). INTERPRETATION: These data show that large numbers of people can rapidly benefit from antiretroviral therapy in rural resource-poor settings and strongly supports the implementation of such large-scale simplified programmes in Africa.

Health related quality of life among both current and former injection drug users who are HIV-infected.

BACKGROUND: This study aimed to determine factors associated with higher levels of health related quality of life (HRQL) among individuals HIV-infected through drug injection and to evaluate the impact of injecting drug status and opiate substitution treatment (OST) on HRQL. METHODS: Two hundred and forty-three patients, enrolled in the MANIF cohort of patients HIV-infected through IDUs, participated. They completed a self-administered questionnaire, which included an HRQL evaluation (SF-12) and socio-demographic/clinical characteristics at the 42-month visit. Injecting drug status, OST and experience of negative life events (NLE) were collected at any follow-up visit in order to reconstitute individual trajectories. RESULTS: Among the 243 patients, 35% reported a normal mental HRQL and 37% a normal physical HRQL. Independent predictors of "normal" mental HRQL were social support from partner, being a former IDU, no experience of violence-related NLE and few self-reported HAART-related side effects. "Normal" physical HRQL was predicted by younger age, stable partner, being a former IDU (> or = 6 months), CD4 cell count > 500, no experience of financial-related NLE and few HAART self-reported side effects. CONCLUSIONS: As HRQL has been found to have a prognostic value on the survival of HIV patients infected through drug injection, then providing more comprehensive care (for example by paying more attention to patients' experience of stressful events, meeting their needs in psychosocial support and better management of perceived toxicity) could globally improve treatment outcomes in this vulnerable population.

A prospective, longitudinal study of sleep disturbance and comorbidity in opiate dependence (the ANRS Methaville study).

RATIONALE/OBJECTIVES: Sleep disturbance is frequent in opioid-dependent patients. To date, no data are available about the impact of methadone maintenance treatment on sleep disturbance. Using 1-year follow-up data from the Methaville trial, we investigated the impact of methadone initiation and other correlates on sleep disturbance in opioid-dependent patients. METHODS: Sleep disturbance severity was evaluated using two items from different scales (Center for Epidemiological Studies Depression Scale for depression and Opiate Treatment Index). We assessed the effect of methadone and other correlates on sleep disturbance severity during follow-up (months 0, 6, and 12) using a mixed multinomial logistic regression model. RESULTS: We included 173 patients who had 1-year follow-up data on sleep disturbance, corresponding to 445 visits. At enrolment, 60.5 % reported medium to severe sleep disturbance. This proportion remained stable during methadone treatment: 54.0 % at month 6 and 55.4 % at month 12. The final multivariate model indicated that younger patients (odds ratio (OR) [95 % CI] 0.95 [0.90-1.00]), patients with pain (OR [95 % CI] 2.45 [1.13-5.32]), patients with high or very high nicotine dependence (OR [95 % CI] 5.89 [2.41-14.39]), and patients at suicidal risk (2.50 [1.13-5.52]) had a higher risk of severe sleep disturbance. Because of collinearity between suicidal risk and attention deficit hyperactivity disorder (ADHD) symptoms, ADHD was not associated with sleep disturbance in the final model. Receiving methadone treatment had no significant effect on sleep disturbance. CONCLUSIONS: Sleep disturbance is frequent among opioid-dependent patients. It can be regarded as an important signal of more complex psychiatric comorbidities such as suicidal risk and ADHD. However, sleep disturbance should not be considered an obstacle to methadone maintenance treatment (MMT) initiation or continuation.

Predictors of non-prescribed opioid use after one year of methadone treatment: an attributable-risk approach (ANRS-Methaville trial).

BACKGROUND: The effectiveness of methadone as an opioid maintenance treatment (OMT) for opioid dependence has been widely demonstrated. However many patients continue to use other opioids while on methadone treatment. Studies assessing avoidable cases of continued non-prescribed opioid use during methadone treatment are sparse. METHODS: At 12 months of treatment (M12), 158 subjects had available data on opioid use, measured using the Opiate Treatment Index. We identified variables associated with non-prescribed opioid use at M12, using a univariate logistic regression and two multivariate models, one incorporating only pre-treatment variables, the second adding the in-treatment variables. We also calculated attributable fractions for risk factors. RESULTS: At M12, 32.3% of the patients had used non-prescribed opioids during the previous month. A good patient-physician relationship was the most influential factor associated with not using non-prescribed opioids after one year. Living with a heroin user after one year of treatment, using cocaine during treatment and hazardous alcohol consumption at enrolment were all associated with an increased risk of non-prescribed opioid use at M12. Analysis of attributable fractions indicated that living with a heroin user at M12 accounted for 21% of patients reporting non-prescribed opioid use at M12, while the lack of a good relationship with the physician accounted for 26%. CONCLUSIONS: The attributable risk approach suggests that continued non-prescribed opioid use by a considerable proportion of individuals could potentially be reduced by improving patient-physician relationships, enhancing care for co-dependent patients and encouraging patients to modify their social network.

What has been achieved in HIV prevention, treatment and care for people who inject drugs, 2010-2012? A review of the six highest burden countries.

OBJECTIVE: In 2010 the international HIV/AIDS community called on countries to take action to prevent HIV transmission among people who inject drugs (PWID). To set a baseline we proposed an "accountability matrix", focusing upon six countries accounting for half of the global population of PWID: China, Malaysia, Russia, Ukraine, Vietnam and the USA. Two years on, we review progress. DESIGN: We searched peer-reviewed literature, conducted online searches, and contacted experts for 'grey' literature. We limited searches to documents published since December 2009 and used decision rules endorsed in earlier reviews. RESULTS: Policy shifts are increasing coverage of key interventions for PWID in China, Malaysia, Vietnam and Ukraine. Increases in PWID receiving antiretroviral treatment (ART) and opioid substitution treatment (OST) in both Vietnam and China, and a shift in Malaysia from a punitive law enforcement approach to evidence-based treatment are promising developments. The USA and Russia have had no advances on PWID access to needle and syringe programmes (NSP), OST or ART. There have also been policy setbacks in these countries, with Russia reaffirming its stance against OST and closing down access to information on methadone, and the USA reinstituting its Congressional ban on Federal funding for NSPs. CONCLUSIONS: Prevention of HIV infection and access to HIV treatment for PWID is possible. Whether countries with concentrated epidemics among PWID will meet goals of achieving universal access and eliminating new HIV infections remains unknown. As long as law enforcement responses counter public health responses, health-seeking behaviour and health service delivery will be limited.

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.

Self-reported side effects in buprenorphine and methadone patients receiving antiretroviral therapy: results from the MANIF 2000 cohort study.

AIMS: The aim of the study was to investigate the relationship between methadone and buprenorphine treatment and self-reported symptoms in HIV-infected opioid dependent individuals receiving antiretroviral therapy (ART). DESIGN: Longitudinal study. SETTING: The French MANIF2000 cohort was used to compare self-reported symptoms in buprenorphine and methadone patients also receiving ART. PARTICIPANTS: We selected individuals receiving ART and OAT (342 visits among 106 patients). MEASUREMENTS: Symptoms were self-reported using a list of 14 symptoms (e.g. nausea, fatigue, fever) perceived during the previous 4 weeks, including three painful symptoms (abdominal or muscular pain, headaches). A two-step Heckman approach enabled us to account for the non-random assignment of OAT: a probit model identified predictors of starting either buprenorphine or methadone. A Poisson regression based on generalized estimating equations (GEE) was then used to identify predictors of the number of symptoms while adjusting for the non-random assignment of OAT. FINDINGS: The median (interquartile range) number of symptoms was 4 (1-6) and 2 (1-6) among buprenorphine and methadone patients, respectively. After adjustment for non-random assignment of OAT type, depressive and opioid withdrawal symptoms, anxiolytics consumption and daily cannabis use, methadone patients were more likely to report a lower number of symptoms than those receiving buprenorphine. CONCLUSIONS: Methadone patients on ART report fewer symptoms than buprenorphine patients on ART under current treatment conditions in France. Further experimental research is still needed to identify an OAT-ART strategy which would minimize the burden of self-reported symptoms and potential interactions, while assuring sustainability and response to both treatments.