Faculty Bibliography

BACKGROUND: Opioid dependence and HIV/AIDS are 2 of the most serious yet treatable diseases worldwide. Global access to opioid agonist therapy and HIV treatment is expanding but when concurrently used, problematic pharmacokinetic drug interactions can occur. METHODS: We reviewed English, Spanish, French, and Italian language articles from 1966 to 2005 in Medline using the following keywords: HIV, AIDS, HIV therapy, antiretroviral therapy, HAART, drug interactions, methadone, and buprenorphine. Additionally, we reviewed abstracts from national and international meetings and conference proceedings. Selected references from these articles were reviewed as well. RESULTS: Clinical case series and carefully controlled pharmacokinetic interaction studies have been conducted between methadone and most approved antiretroviral therapies. Important pharmacokinetic drug interactions have been demonstrated within each class of agents, affecting either methadone or antiretroviral agents. Few studies, however, have been conducted with buprenorphine. The metabolism of both therapies, description of the known interactions, and clinical implications and management of these interactions are reviewed. CONCLUSIONS: Certain interactions between methadone and antiretroviral medications are known and may have important clinical consequences. To optimize care, clinicians must be alert to these interactions and have a basic knowledge regarding their management

Among individuals receiving highly active antiretroviral therapy (HAART), injection drug users (IDUs) are less likely to achieve HIV suppression. The present study examined individual-level, interpersonal, and structural factors associated with achieving undetectable plasma viral load (UVL) among US IDUs receiving recommended HAART. Data were from baseline assessments of the INSPIRE (Interventions for Seropositive Injectors-Research and Evaluation) study, a 4-site, secondary HIV prevention intervention for heterosexually active IDUs. Of 1113 study participants at baseline, 42% (n = 466) were currently taking recommended HAART (34% were female, 69% non-Hispanic black, 26% recently homeless; median age was 43 years), of whom 132 (28%) had a UVL. Logistic regression revealed that among those on recommended HAART, adjusted odds of UVL were at least 3 times higher among those with high social support, stable housing, and CD4 > 200; UVL was approximately 60% higher among those reporting better patient-provider communication. Outpatient drug treatment and non-Hispanic black race and an interaction between current drug use and social support were marginally negatively significant. Among those with high perceived support, noncurrent drug users compared with current drug users had a greater likelihood of UVL; current drug use was not associated with UVL among those with low support. Depressive symptoms (Brief Symptom Inventory) were not significant. Results suggest the major role of social support in facilitating effective HAART use in this population and suggest that active drug use may interfere with HAART use by adversely affecting social support. Interventions promoting social support functioning, patient-provider communication, stable housing, and drug abuse treatment may facilitate effective HAART use in this vulnerable population

This study sought to identify correlates of poor health care utilization among HIV-positive injection drug users (IDUs) using Andersen's behavioural health model. We used baseline data from INSPIRE, a study of HIV-positive IDUs (n=1161) to identify predisposing, enabling, and need factors related to poor utilization (defined as fewer than two outpatient visits in the past six months, or identification of emergency room (ER) as the usual place for care). Using bivariate and multivariate models, we found a number of enabling factors that could facilitate the use of health care services such as having health insurance, having seen a case manager, and better engagement with health care providers. These enabling factors could be modified through interventions targeting HIV-positive IDUs. In addition, health insurance and case management appear to be important factors to address because they contributed in making other factors (e.g. lower education, lack of stable housing) non-significant barriers to outpatient care utilization. In the future, these findings may be used to inform the development of interventions that maximize use of scarce HIV resources and improve health care utilization among HIV-positive IDUs

We evaluated a novel intervention designed to improve access to sterile syringes and safe syringe disposal for injection drug users (IDUs) newly enrolled in methadone maintenance, through interviews with two sequential cohorts of 100 recent entrants into a methadone program in the Bronx, NY. A substantial number of participants had injected in the previous 6 months, and most continued injecting during the early weeks of treatment. The intervention was associated with significant behavior changes among IDUs, including increased use of pharmacies as a primary source of syringes (11% vs. 37%, p < .05) and decreases in both purchasing of syringes on the street (51% vs. 27%, p < .05) and needle sharing (40% vs. 7%, p < .01). The intervention had no impact on the prevalence of injection or on syringe disposal practices. Our findings suggest that drug treatment programs can serve an important role in reducing injection-related risk behavior by facilitating access to sterile syringes

We investigated the characteristics of human immunodeficiency virus (HIV)-positive injection drug-using women who reported unprotected vaginal and/or anal sex with HIV-negative or unknown serostatus (serodiscordant) male partners. Of 426 female study participants, 370 were sexually active. Of these women, 39% (144/370) and 40% (148/370) reported vaginal and/or anal sex with serodiscordant main and casual partners, respectively. Sixty percent of women inconsistently used condoms with their serodiscordant main partners, whereas 53% did so with casual partners. In multivariate analysis, during sex with main partners, inconsistent condom users were less likely to feel confident about achieving safe sex (self-efficacy), personal responsibility for limiting HIV transmission, and that their partner supported safe sex. Inconsistent condom use was also more likely among women who held negative beliefs about condoms and in couplings without mutual disclosure of HIV status. Regarding sex with casual partners, inconsistent condom users were more likely to experience psychologic distress, engage in sex trading, but they were less likely to feel confident about achieving safe sex. These findings suggest that there are widespread opportunities for the sexual transmission of HIV from drug-using women to HIV-uninfected men, and that reasons vary by type of partnership. Multifaceted interventions that address personal, dyadic, and addiction problems are needed for HIV-positive injection drug-using women

ABSTRACT : BACKGROUND : We sought to assess injection practices, means of acquiring and disposing of syringes, and utilization and knowledge of harm reduction resources among injection drug users (IDUs) entering methadone maintenance treatment (MMT). METHODS : Interviews with 100 consecutive patients, including 35 IDUs, entering a MMT program in the Bronx, NY. RESULTS : Utilization of unsafe syringe sources was reported by 69% of IDUs in our sample. Most (80%) IDUs reused syringes, and syringe sharing was also common. Fewer than half knew that non-prescription pharmacy purchase of syringes was possible. The most common means of disposing of injecting equipment were the trash (63%) and syringe exchange programs (49%). CONCLUSIONS : These findings indicate that drug users entering treatment under-utilize sanctioned venues to obtain sterile syringes or safely dispose of used injection equipment. Programs providing services to drug users should adopt a proactive stance to address the safety and health issues faced by injectors

Understanding the drug interactions between antiretrovirals and opioid therapies may decrease toxicities and enhance adherence with improved HIV outcomes in opioid-dependent individuals. The authors report the results of a clinical pharmacology study designed to determine whether significant pharmacokinetic and/or pharmacodynamic interactions occur between the non-nucleoside reverse transcriptase inhibitor, delavirdine (DLV), and either methadone or levo-alpha acetyl methadol (LAAM) (n = 40). DLV significantly decreased methadone clearance (p = .018) and increased the methadone elimination half-life (p < .001) with a resultant increase in AUC of 19% and C(min)of 29%. The combined effect of DLV on the total concentration of LAAM and its active metabolites, norLAAM and dinorLAAM, was to significantly increase AUC by 43% (p < .001), C(max) by 30% (p = .013), and C(min) by 59% (p = .004) while decreasing T(max) (p = .05). Cognitive deficits over the seven-day study period as measured by the Mini-Mental State Examination, opioid withdrawal symptoms as measured by the Objective Opioid Withdrawal Scale, or complaints of adverse symptoms were not observed. Methadone and LAAM did not affect DLV concentrations. The findings from this study show that DLV treatment in methadone- or LAAM-maintained individuals results in altered opioid pharmacokinetics with an increased exposure and potential risk for opioid toxicity with methadone or LAAM treatment and an increased risk of cardiac toxicity with concomitant LAAM and DLV administration

Opioid dependence is a chronic and relapsing medical disorder with a well-established neurobiological basis. Opioid agonist treatments, such as methadone and the recently approved buprenorphine, stabilize opioid receptors and the intracellular processes that lead to opioid withdrawal and craving. Both methadone and buprenorphine have been proven effective for the treatment of opioid dependence and can contribute to a decreased risk of human immunodeficiency virus (HIV) transmission. In addition, a buprenorphine/naloxone combination appears to have a decreased potential for abuse or diversion, compared with that associated with methadone. Largely because of these properties, recent legislation now affords an unprecedented opportunity for general physicians to offer opioid agonist treatment through their offices. This review focuses on the neurobiological basis of opioid dependence, the rationale for methadone and buprenorphine treatments, and issues in prescribing these medications to patients with HIV infection

Methadone medical maintenance (MMM) is a model for the treatment of opioid dependence in which a monthly supply of methadone is distributed in an office setting, in contrast to more highly regulated settings where daily observed dosing is the norm. We assessed patient characteristics and treatment outcomes of an MMM program initiated in the Bronx, New York, in 1999 by conducting a retrospective chart review. Participant characteristics were compared with those of patients enrolled in affiliated conventional methadone maintenance treatment programs. Patients had diverse ethnicities, occupations, educational backgrounds, and income levels. Urine toxicology testing detected illicit opiate and cocaine use in 0.8% and 0.4% of aggregate samples, respectively. The retention rate was 98%, which compares favorably with the four other MMM programs that have been reported in the medical literature. This study demonstrates that selected patients from a socioeconomically disadvantaged population remained clinically stable and engaged in treatment in a far less intensive setting than traditional methadone maintenance