Search

Baclofen has been shown to reduce alcohol consumption in alcohol-dependent individuals, but there is marked heterogeneity in response. An association between GABBR1 rs29220 and alcohol dependence has been demonstrated previously. The present study evaluated whether the response to baclofen is moderated by a single nucleotide polymorphism (rs29220) in the GABAB receptor subunit 1 gene (GABBR1).Double-blind, placebo-controlled study.Australia.Seventy-two alcohol-dependent men and women receiving 12 weeks of 30 mg/day of baclofen, 75 mg baclofen or placebo.Primary outcomes included time to lapse (any drinking) and relapse (5 drinks per day in men and 4 in women). We also examined alcohol consumption at follow-up (drinks per drinking day, number of heavy drinking days and percentage days abstinent).We observed significant medication × genotype interaction effect for time to relapse (P = 0.049) and a near-significant interaction effect for time to lapse (P = 0.055). For the CC genotype group, the relapse hazard ratio for baclofen versus placebo was 0.32 [95% confidence interval (CI) = 0.14-0.75] and for the G- group it was 1.07 (95% CI = 0.43-2.63). There was also a significant medication × genotype interaction for follow-up alcohol consumption (drinks per drinking day, heavy drinking days and days abstinent) (P = 0.02). Covarying for baseline levels of craving, aspartate aminotransferase and abstinence before enrolment reduced the medication × genotype effect for time to lapse and relapse but not for alcohol consumption at follow-up.The GABBR1 rs29220 polymorphism may influence treatment response and possibly predict adverse effects to baclofen in the treatment of alcohol dependence.

To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response.Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1).Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia.Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female).Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA24 weeks post-treatment).Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on-treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR.People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy.