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Aims: Opioids have been hypothesized to suppress the immune function and worsen outcomes among people living with human immunodeficiency virus (HIV). The study aimed to identify key factors associated with the increased cluster of differentiation 4 (CD4) cell counts among HIV-positive people who inject heroin and receive methadone maintenance treatment (MMT)., Methods: This longitudinal study was conducted at a psychiatric hospital in Northern Taiwan. Participants were recruited from 2006 through 2011, and received CD4 cell counts and HIV viral load monitoring once every 4 to 6 months. Trend in CD4 cell counts, defined as change in CD4 cell count over time, was used as the outcome measure. Independent variables included MMT-related factors and baseline characteristics. Baseline characteristics included age, gender, CD4 cell count, HIV viral load, tests for other infections, liver function tests, and urine drug screens., Results: Three hundred and fifty one participants were recruited during the study period. The multivariate linear mixed model analysis revealed a higher MMT attendance rate, a higher baseline CD4 cell count, and a shorter duration of MMT were associated with an increase in CD4 cell count over time., Conclusions: The study showed better adherence to MMT was associated with better preserved immune functions. The negative impact of duration of MMT on CD4 cell counts may be ameliorated by improving the attendance rate, initiation of MMT earlier when the baseline CD4 cell count is still relatively high and by the other beneficial effects of MMT, such as healthier lifestyles with reduced use of short-acting opioids.

Methadone, a synthetic racemic opioid that primarily works as a μ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients., (Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.)

Aim: Methadone maintenance therapy is one of the standard treatments for heroin addiction. The isozyme CYP3A4 of the CYP system is one of the metabolic enzymes, as well as CYP2B6, responsible for the metabolism of methadone. The aim of the present study is to evaluate the potential use of genetic polymorphisms in CYP3A4 as biomarkers for the prediction of methadone treatment responses., Materials & Methods: A total of 366 Han Chinese methadone maintenance treatment patients in Taiwan were recruited in this study. Main clinical assessments included the clinical opioid withdrawal scale (COWS), the treatment emergent symptom scale (TESS) and the plasma concentrations of methadone and its metabolites. Genetic associations of six SNPs in the CYP3A4 gene were calculated using a general linear model., Results: Genotypes and allele types of rs4646440 and rs2242480 were found to be significantly associated with the severity of withdrawal symptoms rated by COWS (p = 0.012, 0.0096, 0.017 and 0.012, respectively) as well as the side effects rated by TESS (p = 0.0089, 0.028, 0.0027 and 0.0085, respectively). The allele types associated with more severe withdrawal symptoms are also associated with more severe side effects and less betel nut (Areca catechu) use (p = 0.009 for rs4646440, p = 0.0063 for rs2242480). Further analyses on specific withdrawal symptoms in COWS showed that the genetic variants in rs4646440 are significantly associated with heart rate (allele type p = 0.0019)., Conclusion: These results suggested that genetic variants in the CYP3A4 gene may be useful indicators for the severity of side effects and withdrawal symptoms for methadone treatment.