Approximately 30% of AIDS patients are injection drug abusers, and current data indicates that over half of new AIDS cases in New York City, New Haven, and many other Northeast urban areas occur in this population. This group is not only at risk, but is a major vector for transmission of HIV. Despite this, injection drug abusers are seriously under represented in most clinical protocols. Little is known regarding optimal pharmacotherapeutic treatment for opioid-dependent patients with HIV disease,. Compliance with HIV disease medication treatments is a significant problem in the HIV-positive, drug abusing population. We have recently reported a significant increase in plasma AZT concentrations in opioid-dependent, methadone-maintained patients with HIV disease who are treated with AZT. We have observed an increase in area under the oral AZT concentration-time curve ranging from 25% to 80% (mean 52%, p=03) following administration of methadone. In addition, methadone treated patients have reported dysphoria, insomnia, and malaise following imitation of AZT treatment which could be related to increased AZT exposure. We now propose to determine whether other drugs used to treat opiate dependence have significant effects on AZT disposition. Subjects maintained on either buprenorphine, LAAM, or naltrexone who are also being treated with AZT will participate in a pharmacokinetic study. Blood and urine samples will be collected at predetermined time points following administration of AZT. Findings from these samples will be compared with those in 2 control samples: 1. recently detoxified opioid-dependent patients treated with AZT and 2. patients with no substance use disorders who are treated with AZT. We also plan to identify whether drugs used to treat opiate dependence alter the disposition of other new antiretroviral agents used to treat HIV disease in later years of this grant. The proposed studies represent a method for identification of potential drug interactions in this population which is cost-effective. These investigations will make a significant contribution to improved medical and substance abuse treatment in opioid-dependent patients with HIV disease.
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