Optimizing assessment and treatment for hepatitis C virus infection in illicit drug users: a novel model incorporating multidisciplinary care and peer support.

OBJECTIVES: We evaluated assessment and treatment for hepatitis C virus (HCV) among illicit drug users accepting referral to a weekly HCV peer-support group at a multidisciplinary community health centre. METHODS: From March 2005 to 2008, HCV-infected individuals were referred to a weekly peer-support group and assessed for HCV infection. A retrospective chart review of outcomes 3 years after the initiation of the group was conducted (including HCV assessment and treatment). RESULTS: Two hundred and four HCV antibody-positive illicit drug users accepted referral to a weekly HCV peer-support group. Assessment for HCV occurred in 53% of patients(n= 109), with 13% (n= 14) having initiated or completed treatment for HCV infection before attending the support group, evaluation ongoing in 10% (n= 11) and treatment deferred/not indicated in 25% (n= 27). The major reasons for HCV treatment deferral included early disease (30%),drug dependence (37%), other medical (11%) or psychiatric comorbidities (4%). Sixty-eight percent of those deferred for reasons other than early liver disease showed multiple reasons for treatment deferral. The first 4 weeks of support group attendance predicted successful HCV assessment (odds ratio: 6.03, 95% confidence interval:3.27-11.12, P < 0.001). Overall, 28% (n= 57) received treatment. Among individuals having completed pegylated-interferon and ribavirin therapy with appropriate follow-up (n =19), the rate of sustained virologic response was 63% (12/19), despite illicit drug use in 53%. CONCLUSION: A high proportion of illicit drug users accepting referral to a weekly HCV peer-support group at a multidisciplinary health centre were assessed and treated for HCV infection. Peer support coupled with multidisciplinary care is an effective strategy for engaging illicit drug users in HCV care.

Primary drug resistance in antiretroviral-naïve injection drug users.

OBJECTIVES: We evaluated the prevalence of primary HIV drug resistance in a population of 128 injection drug users (48 female) prior to initiating antiretroviral therapy. METHODS: Genotypic and phenotypic profiles were obtained retrospectively for the period June 1996 to February 2007. Genotypic drug resistance was defined as the presence of a major mutation (IAS-USA table, 2007 revision), adding revertants at reverse transcriptase (RT) codon 215. Phenotypic drug resistance was defined as the fold change associated with >or=80% loss of the wild type virologic response due to viral resistance based on virtual phenotype analysis. RESULTS: Genotypic drug resistance was uncommon, and was only identified in six (4.7%) cases, all in the RT gene (L100I, K103N, Y181C, M184V, Y188L, and T215D). There were no cases of multi-class or protease inhibitor (PI) resistance. However, polymorphisms in the protease and RT genes were extremely common. Phenotypic drug resistance was also identified in six (4.7%) patients, four in the RT gene (in patients with mutations K103N, Y181C, M184V and Y188L) and two the protease gene (in two patients with minor PI mutations). In addition, 25 (19.5%) of the patients had reduced susceptibility to PIs, defined as resistance>20% but <80% of the wild type virologic response, with no primary PI mutations detected in all these patients. CONCLUSION: The prevalence of primary HIV drug resistance was low in this population of injection drug users.

Current approaches to HCV infection in current and former injection drug users.

Injection drug use (IDU) accounts for 75% of incident cases of hepatitis C virus (HCV) infection in the developed world. Of those infected with HCV, up to 80% will go on to develop chronic disease. Intervention with effective treatment in eligible subjects will limit the impact of the long-term consequences of infection. The use of combination therapy with pegylated interferon and ribavirin may lead to a cure in up to 80% of treated individuals who carry genotype 2 or 3 isolates. Such individuals account for up to 45% of certain cohorts, such as in the inner city of Vancouver. Historically, many IDUs have not received treatment for HCV infection even if it were medically indicated. Recent data (including our own) suggest that, in the right context, response rates similar to those reported in clinical trials of HCV therapy can be achieved in IDUs, even with ongoing drug use. This is all the more important given that prior infection may protect against re-infection even in the presence of ongoing risk behaviors for HCV transmission. The keys to a successful program appear to be appropriate patient selection as well as the delivery of care within an appropriate setting, preferably with a multidisciplinary team in a way that addresses the issue of addiction and other conditions simultaneously. The development of such programs may be quite complex, but the ultimate benefit (for the treated population and for society as a whole) is certainly worth the effort.

Treatment uptake and outcomes among current and former injection drug users receiving directly observed therapy within a multidisciplinary group model for the treatment of hepatitis C virus infection.

Injection drug use accounts for the majority of incident and prevalent cases of hepatitis C virus (HCV) infection. However, very few injection drug users (IDUs) have received treatment for this condition given issues of medical or psychiatric co-morbidity, ongoing substance abuse and a widely held belief that such individuals will not be able to adhere to the requirements of therapy, including regular medical follow-up. With this in mind, we sought to evaluate HCV treatment uptake and outcomes among current and former IDUs attending a weekly peer support group and receiving directly observed HCV therapy. Utilizing the existing infrastructure for the management of addictive disease, we have developed a model of "one-stop shopping" whereby the treatment of addiction, HCV and other medical conditions are fully integrated, with the collaboration of nurses, counsellors, addiction specialists, infectious disease specialists, primary care physicians and researchers. Subjects interested in receiving treatment for HCV infection were referred to a weekly peer-support group and evaluated for treatment. Patients received therapy with pegylated interferon-alpha2a or -alpha2b, both in combination with ribavirin. All injections were directly observed. Overall, we observed a high uptake of HCV treatment among attendees, with 51 percent either receiving or about to receive therapy. To date, 18 patients have initiated treatment for HCV infection and 12 have completed therapy. Overall, 8/12 (67 percent) subjects achieved an end of treatment response (genotype 1, 67 percent; genotypes 2/3, 67 percent), despite ongoing drug use in 75 percent of patients during treatment. These data demonstrate that with the appropriate programs in place, a high uptake of HCV treatment can be achieved among IDUs referred to a peer-support group. Moreover, the treatment of HCV in current and former IDUs within a multidisciplinary DOT program can be successfully undertaken, resulting in ETRs similar to those reported in randomized controlled trials.

Directly observed therapy for the treatment of hepatitis C virus infection in current and former injection drug users.

BACKGROUND AND AIM: There are few studies investigating the treatment of hepatitis C virus (HCV) infection in current and former drug users. With this in mind, we sought to evaluate the antiviral efficacy of interferon alpha-2b (IFN alpha-2b) or pegylated-interferon alpha-2b (PEG-IFN alpha-2b) and ribavirin (RBV) in injection drug users (IDU) enrolled in a directly observed therapy (DOT) program, as measured by sustained virologic response (SVR). METHODS: Viremic HCV-infected IDU, with alanine aminotransferase (ALT) >1.5x upper limit of normal (ULN) were offered 24-48 week (based on HCV genotype) therapy with RBV (800-1200 mg/day, based on weight) along with IFN alpha-2b (3 million IU thrice weekly) replaced by PEG-IFN alpha-2b (1.5 ìg/kg once weekly) as it became available. All injections were directly observed. The primary endpoint was SVR. RESULTS: Overall, 40 patients (33 males) received IFN alpha-2b (12) or PEG-IFN alpha-2b (28), 55% with HCV genotypes 2 or 3. Only 14 discontinued therapy, 5 due to toxicity, 6 due to illicit drug use and 3 did not achieve an early virologic response. In an intent-to-treat analysis, the overall SVR was 55% (22/40), 64% (14/22) in subjects with genotypes 2/3. There was no significant difference in response rates among those with >6 (50%) or

Methadone dosing strategies in HIV-infected injection drug users enrolled in a directly observed therapy program.

OBJECTIVES: We have measured methadone dose adjustments and treatment responses after nevirapine (NVP)-, efavirenz (EFV)-, ritonavir-boosted lopinavir (LPV/r), or atazanavir (ATV; with or without ritonavir)-based highly active antiretroviral therapy (HAART) was initiated in injection drug users (IDUs). METHODS: We identified 120 IDUs receiving HAART and methadone within a directly observed therapy (DOT) program. Follow-up was according to clinical standards, with changes in methadone dose being made as required to achieve clinical stabilization within the first 3 months of HAART. RESULTS: The observed median methadone dose changes from baseline were 20 mg/d (P<0.001) in patients on NVP, with 32 (86%) of 37 patients requiring daily dose increases, and 7.5 mg/d (P=0.004) in patients on EFV, with 11 (61%) of 18 patients requiring daily dose increases. Conversely, median changes were 0 mg/d for patients on LPV/r (P=0.56) or ATV (P=0.95). Virologic suppression (HIV RNA<400 copies/mL) was achieved in 26 (70%) of 37, 12 (67%) of 18, 25 (76%) of 33, and 24 (75%) of 32 patients receiving NVP-, EFV-, LPV/r-, and ATV-based regimens, respectively (P=0.89). CONCLUSIONS: Although methadone-based DOT can be a successful tool for the coadministration of HAART, careful monitoring is required to ensure that methadone withdrawal does not adversely affect the goals of treatment, particularly when nonnucleoside reverse transcriptase inhibitors are used.

The impact of ongoing illicit drug use on methadone adherence in illicit drug users receiving treatment for HIV in a directly observed therapy program.

INTRODUCTION: Studies evaluating the effectiveness of opioid agonist therapy programs typically evaluate drug abstinence or treatment retention as their primary outcomes. However, in many circumstances (e.g. directly observed therapy (DOT) programs within methadone maintenance programs), methadone adherence is an extremely relevant clinical outcome. We sought to evaluate the impact of ongoing illicit drug use on methadone adherence within a DOT program for the treatment of HIV-infection. METHODS: Patients were enrolled in a DOT program, where methadone and HIV medication are co-administered by a community pharmacist. Drug use (amphetamines, benzodiazepines, cocaine, and opiates) was assessed by repeated urinalysis results. Methadone adherence was calculated as the fraction of days methadone was administered. RESULTS: Ongoing drug use, and poly-substance use was common, with only 4 of 60 patients abstaining from all illicit drug use. Overall methadone adherence was 84.5%. Amphetamine use (without benzodiazepine and cocaine use), benzodiazepine use (without amphetamines) and higher methadone doses were associated with higher methadone adherence. When patients used benzodiazepines or cocaine, any positive effect associated with amphetamine use was negated. In addition, opiate use was associated with decreased methadone adherence. DISCUSSION: The effect of many illicit drugs on methadone adherence may differ from reports using other treatment outcomes.

Clinical implications of mutations at reverse transcriptase codon 135 on response to NNRTI-based therapy.

To evaluate the impact of mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy, a total of 68 patients (30 with and 38 without baseline mutations at codon 135) were evaluated. Median increases in CD4 counts were 135 and 90 cells/mm(3) (p=0.32), virologic suppression (HIV RNA < 400 copies/mL) was achieved in 16 (53%) and 16 (42%) patients (p=0.50), while NNRTI resistance was detected in 10/14 (71%) and 16/22 (73%) in patients with and without mutations at codon 135, respectively. Patients who experienced a virologic breakthrough and had a baseline mutation at codon 135 were more likely to evolve a single NNRTI resistance mutation (8/14 vs 4/22, p=0.029) but less likely to evolve multiple NNRTI resistance mutations (2/14 vs 12/22, p = 0.033). Mutations at codon 135 do not affect response rates, but affect the pattern of development of NNRTI resistance mutations. This has important implications for the subsequent use of newer NNRTIs such as etravirine in salvage therapy.