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

International audienceObjective: 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

The Effects of FGF4 Retrogenes on Canine Morphology

Two FGF4 retrogenes (FGF4L1 on chromosome 18 and FGF4L2 on chromosome 12) have been identified to cause dwarfism across many dog breeds. Some breeds are nearly homozygous for both retrogenes (e.g., Dachshunds) and others are homozygous for just one (e.g., Beagles and Scottish Terriers). Since most breeds do not segregate both of these retrogenes, it is challenging to evaluate their individual effects on long bone length and body size. We identified two dog breeds selected for hunting ability, the Alpine Dachsbracke and the Schweizer Niederlaufhund, that segregate both of these retrogenes. Using individual measurements of height at the shoulder, back length, head width, thorax depth and width, and thoracic limb measurements, we evaluated the combined effects of FGF4 retrogenes within these breeds. We applied multivariable linear regression analysis to determine the effects of retrogene copy numbers on the measurements. Copy numbers of both retrogenes had significant effects reducing height at the shoulders and antebrachial length, with FGF4L1 having a much greater effect than FGF4L2. FGF4L1 alone influenced the degree of carpal valgus and FGF4L2 alone increased head width. Neither retrogene had an effect on thorax width or depth. Selectively breeding dogs with FGF4L1 and without FGF4L2 would likely lead to a reduction in the FGF4L2-related risk of intervertebral disc herniation while maintaining the reduction in leg length resulting from FGF4L1

Nutrients

BACKGROUND: Coffee intake has been shown to modulate both the effect of ethanol on serum GGT activities in some alcohol consumers and the risk of alcoholic cirrhosis in some patients with chronic diseases. This study aimed to analyze the impact of coffee intake and alcohol consumption on advanced liver fibrosis (ALF) in HIV-HCV co-infected patients. METHODS: ANRS CO13-HEPAVIH is a French, nationwide, multicenter cohort of HIV-HCV-co-infected patients. Sociodemographic, behavioral, and clinical data including alcohol and coffee consumption were prospectively collected using annual self-administered questionnaires during five years of follow-up. Mixed logistic regression models were performed, relating coffee intake and alcohol consumption to ALF. RESULTS: 1019 patients were included. At the last available visit, 5.8% reported high-risk alcohol consumption, 27.4% reported high coffee intake and 14.5% had ALF. Compared with patients with low coffee intake and high-risk alcohol consumption, patients with low coffee intake and low-risk alcohol consumption had a lower risk of ALF (aOR (95% CI) 0.24 (0.12(-)0.50)). In addition, patients with high coffee intake had a lower risk of ALF than the reference group (0.14 (0.03(-)0.64) in high-risk alcohol drinkers and 0.11 (0.05(-)0.25) in low-risk alcohol drinkers). CONCLUSIONS: High coffee intake was associated with a low risk of liver fibrosis even in HIV-HCV co-infected patients with high-risk alcohol consumption

Adherence as a Predictor of Sexual Behaviors in People Living with HIV/AIDS during the First Year of Antiretroviral Therapy in Rural Cameroon: Data from Stratall ANRS 12110/ESTHER Trial

Objective: This study aims to investigate the time pattern of inconsistence condom use (ICU) during the first year of antiretroviral therapy (ART) and its relationship with treatment adherence in naive HIV-infected adult patients. ' Methods: Data collection was nested within a longitudinal trial on HIV treatment. ICU was defined as reporting to have "never", "sometimes" or "nearly always" used condoms with one's main or casual partner(s) - either HIV-negative or of unknown HIV status in the three previous months. Adherence was defined as taking 100% of their ART prescribed doses in the 4 days before the visit and "not having interrupted treatment", even once, for more than two consecutive days during the 4 previous weeks. Mixed logistic regression was used to study the relationship between adherence and ICU. Results: Among the 459 patients enrolled, 212 (46%) during 334 visits reported to have had sexual intercourse at least once with their partner(s) - either HIV-negative or of unknown HIV status-during the first 12 months of ART. The proportion of ICU was 76%, 50% and 59% at month 0 (M0), month 6 (M6) and month 12 (M12), while 60% and 66% of patients were ART-adherent at M6 and M12, respectively. After adjustment for the frequency of sexual activity, type of sexual partner(s), perceived social class and desire for a child, patients adherent to ART were less likely to report ICU when compared with baseline (AOR [95% CI]: 0.38 [0.19-0.76]; P = 0.006). Conclusions: Adherence to ART is associated with a lower risk of ICU but this result needs to be interpreted carefully. As adherence behaviors are not only determined by problems with the healthcare systems but also by social barriers encountered by patients in their daily life, counseling should not only be ART adherence-centered but also patient-centered, including sexual risk minimization and psychosocial support

PLoS One

BACKGROUND: Direct-acting antivirals (DAA) have dramatically increased HCV cure rates with minimal toxicity in HIV-HCV co-infected patients. This study aimed to compare the socio-behavioral characteristics of patients initiating pegylated-interferon (PEG-IFN)-based HCV treatment with those of patients initiating DAA-based treatment. METHODS: ANRS CO13 HEPAVIH is a national multicenter prospective cohort started in 2005, which enrolled 1,859 HIV-HCV co-infected patients followed up in French hospital outpatient units. Both clinical/biological and socio-behavioral data were collected during follow-up. We selected patients with socio-behavioral data available before HCV treatment initiation. RESULTS: A total of 580 patients were included in this analysis. Of these, 347 initiated PEG-IFN-based treatment, and 233 DAA-based treatment. There were significant differences regarding patient mean age (45 years+/-6 for the PEG-IFN group vs. 52 years+/-8 for the DAA group, p<0.001), unstable housing (21.4% vs. 11.2%, p = 0.0016), drug use (44.7% vs. 29.6%, p = 0.0003), regular or daily use of cannabis (24.3% vs. 15.6%, p = 0.0002), a history of drug injection (68.9% vs 39.0%, p<0.0001) and significant liver fibrosis (62.4% vs 72.3%, p = 0.0293). In multivariable analysis, patients initiating DAA-based treatment were older than their PEG-IFN-based treatment counterparts (aOR = 1.17; 95%CI [1.13; 1.22]). Patients receiving DAA treatment were less likely to report unstable housing (0.46 [0.24; 0.88]), cannabis use (regular or daily use:0.50 [0.28; 0.91]; non-regular use: 0.41 [0.22; 0.77]), and a history of drug injection (0.19 [0.12; 0.31]). CONCLUSION: It is possible that a majority of patients who had socio-economic problems and/or a history of drug injection and/or a non-advanced disease stage were already treated for HCV in the PEG-IFN era. Today, patients with unstable housing conditions are prescribed DAA less frequently than other populations. As HCV treatment is prevention, improving access to DAA remains a major clinical and public health strategy, in particular for individuals with high-risk behaviors

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Perceptions and behaviors of people living with HIV/AIDS with hepatitis C virus co-infection

En France, de 25000 à 30 000 personnes sont co-infectées par le VIH et le virus de l’hépatite C (VHC), avec des conséquences cliniques majeures. Des progrès importants ont été accomplis ces dernières années grâce au développement de nouveaux traitements contre le VHC, efficaces et très bien tolérés. En parallèle, le nombre de patients co-infectés a globalement baissé parmi les patients infectés par le VIH, mais de nouveaux groupes à risque de transmission du VHC sont apparus dans cette population, comme les hommes ayant des rapports sexuels avec d’autres hommes. Le vécu de la co-infection reste peu documenté. Cette thèse analyse les perceptions (qualité de vie, impact fonctionnel de la fatigue) et les comportements (sexuels, addictifs) des patients co-infectés, en lien avec l’évolution de leurs paramètres cliniques, et évalue comment utiliser ces données pour améliorer la prise en charge de la co-infection et mieux cibler les actions de prévention de la transmission du VHC.Between 25,000 and 30,000 people are co-infected with HIV and hepatitis C virus (HCV) in France, with major clinical repercussions. Major therapeutic advances have been made in recent years thanks to the development of direct-acting antivirals for HCV treatment, with very good efficacy and safety profiles. In the same time, while the number of co-infected patients has globally decreased among HIV-infected patients, new groups at risk of HCV transmission have emerged in this population, such as men who have sex with men (MSM). Co-infected patients’ day-to-day experience with the disease remains poorly documented. In this work, we analyze the perceptions (quality of life, functional impact of fatigue) and behaviors (sexual risk behaviors, addictive behaviors) of co-infected patients and their relationships with clinical parameters, and we try to determine to what extent such data can be used to improve the management of co-infection and to better target HCV prevention actions

HÉPATITES VIRALES : Épidémiologie et prévention vaccinale de l’hépatite B

National audienc

HÉPATITES VIRALES : Épidémiologie et prévention vaccinale de l’hépatite B

National audienc