A Randomized Trial of a Hepatitis Care Coordination Model in Methadone Maintenance Treatment

American Journal of Public Health
October 2013, Vol. 103, No. 10 : pp. e81-e88

Carmen L. Masson, Kevin L. Delucchi, Courtney McKnight, Jennifer Hettema, Mandana Khalili, Albert Min, Ashly E. Jordan, Nicole Pepper, Jessica Hall, Nicholas S. Hengl, Christopher Young, Michael S. Shopshire, Jennifer K. Manuel, Lara Coffin, Hali Hammer, Bradley Shapiro, Randy M. Seewald, Henry C. BodenheimerJr, James L. Sorensen, Don C. Des Jarlais, and David C. Perlman

(doi: 10.2105/AJPH.2013.301458)

ABSTRACT

Objectives. We evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients.

Methods. We conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services.

Results. Compared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV–HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61).

Conclusions. Hepatitis care coordination was efficacious in increasing adherence to HAV–HBV vaccination and HCV clinical evaluation among methadone patients.

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Methadone Linked to Prolonged QTc Interval

September 5, 2013

Keith Henry, MD reviewing Vallecillo G et al. Clin Infect Dis 2013 Aug 14. Keith Henry, MD

A prolonged QTc interval in HIV-infected patients on methadone was associated with higher methadone doses, hepatitis C liver disease, and ART-naive status. Keith Henry, MD

Illicit opioid use is associated with increased risk for HIV infection. Methadone is an effective drug for the long-term management of opioid-dependent HIV-infected patients, although safety concerns have been identified (i.e., cardiac arrhythmias such as prolonged QTc interval and torsades de pointes).

In a cross-sectional study, HIV-infected patients on methadone maintenance therapy followed at a single outpatient clinic in Spain underwent 12-lead electrocardiography 24 hours after supervised methadone administration. Individuals with known cardiac disease, drug-positive urine tests, electrolyte abnormalities, or changes in antiretroviral therapy (ART) regimen or methadone dose in the preceding 2 months were excluded.

Of the 91 study participants (64% men; 100% white; median age, 44.5), 68 (75%) were on ART; the regimen for 56 of them included a boosted protease inhibitor. The median nadir and current CD4 counts were 232 and 438 cells/mm3, respectively. The median methadone dose was 70 mg/day, and the mean QTc interval was 438 milliseconds. A prolonged QTc interval (>450 ms) was documented in 33 participants (36%), including 3 with intervals >500 milliseconds. On multiple linear regression analysis, higher methadone dose, chronic hepatitis C–induced cirrhosis, and ART-naive state were associated with a prolonged QTc interval.

Comment

In a cross-sectional study without a control population, it is difficult to fully assess the clinical risk posed by the reported QTc abnormalities.

A prolonged QTc interval was associated with being antiretroviral-naive, but was not observed with use of protease inhibitors (which have been linked in other studies to QTc prolongation). Complicating the situation was the common use of other QTc-prolonging drugs (58% of the participants were taking antipsychotics, antidepressants, antiepileptics, or antibiotics). The study findings remind clinicians of the possible effects of drugs on cardiac conduction and the need to be diligent in monitoring for potential problems (often including input from an HIV-savvy pharmacist, as well as baseline and follow-up electrocardiograms).

Citation(s):

Vallecillo G et al. Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. Clin Infect Dis 2013 Aug 14; [e-pub ahead of print]. (http://dx.doi.org/10.1093/cid/cit467)

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Methadone Cuts HIV Risk

By Michael Smith, North American Correspondent, MedPage Today

Published: October 04, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston

Injection drug users on opiate substitution treatment with methadone cut their risk of HIV infection by more than half, researchers reported.

In a systematic review and meta-analysis, people on methadone treatment had a 54% reduction in the risk of HIV compared with the usual incidence of the infection seen among injection drug users, according to Georgie MacArthur, BSc, of the University of Bristol in Bristol, England, and colleagues.

The finding "supports calls for the global increase of harm reduction interventions" aimed at injection drug users, MacArthur and colleagues argued online in BMJ.

The estimated prevalence of HIV is about 40% among the world's roughly 16 million injection drug users, the researchers noted, and injection drug use has driven several recent HIV outbreaks in Europe.

A standard approach to treating addiction is opiate substitution with methadone or buprenorphine (Subutex) but there has been no quantitative estimate of the effect of substitution therapy on HIV transmission.

To help fill the gap, MacArthur and colleagues conducted a systematic review, looking for data on how opioid substitution affected HIV incidence.

All told, they found 12 published studies with data on the effect of substitution treatment on HIV transmission, and they obtained unpublished data from three other studies.

All of the 15 studies looked at methadone substitution, they reported.

For a meta-analysis, data from nine studies – from the U.S., Canada, the U.K., The Netherlands, Austria, Italy, Thailand, Puerto Rico, and China -- could be pooled, they found, including 819 new HIV infections over 23,608 person years of follow-up.

The analysis showed "strong evidence" of a benefit: the rate ratio was 0.46, with a 95% confidence interval from 0.32 to 0.67, which was significant at P<0.001.

MacArthur and colleagues cautioned, however, that there was heterogeneity between studies that "could not be explained by geographical region, site of recruitment, or the provision of incentives."

Not all of the studies adjusted for confounding factors, but analysis of a subset of six that did still suggested that methadone substitution was associated with a 40% reduction in HIV risk.

The researchers cautioned that all of the included studies were observational and subject to both selection and attrition bias.

"The extent to which the studies were representative of all people who inject drugs and are receiving opiate substitution treatment is unclear," they noted.

Despite such limitations, however, the findings are "strong quantitative evidence of an association between opiate substitution treatment and reduced risk of HIV transmission among people who inject drugs," they concluded.

The study is a bookend to an earlier systematic review that found that substitution treatment reduced activities associated with a high risk of HIV transmission, according to Linda Gowing, PhD, of the University of Adelaide in Adelaide, Australia.

Taken together, the two studies "provide strong evidence" that the treatment – at least with methadone -- cuts both high-risk behavior and the risk of acquiring HIV, Gowing argued in an accompanying editorial.

She cautioned that the benefits of substitution therapy are likely to be lost when treatment stops -- especially if the treatment is not voluntary -- or when patients relapse and resume injecting drugs.

Policymakers, she argued, should aim at "maximizing the proportion of injecting drug users in the treatment program and promoting their retention" in care.

The study had support from the Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Medical Research Council, the Welsh Assembly Government and the Wellcome Trust.

The journal said MacArthur did not report any conflicts.

The journal said Gowing did not report any conflicts.

Primary source: BMJ
Source reference:
MacArthur GJ, et al "Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis" BMJ 2012; 345: e5945.

Additional source: BMJ
Source reference:
Gowing LR "The role of opioid substitution treatment in reducing HIV transmission" BMJ 2012; 345: e6425.

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