The proposed study was formulated in response to RFA HL-98-012 requesting applications to investigate cardiovascular complications from cocaine abuse in HIV infection, with a focus on the call for clinical studies to identify effective treatment protocols. Cocaine use by HIV-positive individuals represents a primary vector of infection to non-infected individuals, and may also adversely affect disease progression, including increasing risk for cardiovascular dysfunction. A treatment approach targeting both cocaine use and cardiovascular disorders simultaneously would therefore be extremely beneficial in an HIV- positive, cocaine-abusing patient population. The proposed study capitalizes on the multiple effects of the angiotensin converting enzyme (ACE) inhibitor, fosinopril, in numerous tissue systems, and will investigate its ability to reduce cocaine use through activity in the brain, and to reverse or prevent the cardiotoxic effects of cocaine and HIV disease by actions upon the heart and cardiovascular system, including platelet aggregation factors. In the proposed five-year study, one hundred and twenty-four HIV- positive cocaine-dependent methadone-maintained patients will be randomly assigned to receive either fosinopril (20 mg/day) or placebo for six months.
The specific aims of this study are: (a) to investigate the efficacy of fosinopril for the treatment of cocaine dependence in HIV-positive methadone-maintained patients, based on twice weekly urine toxicology screens; (b) to determine the ability of fosinopril to improve cardiac functioning by comparing pre- and post-treatment two-dimensional and Doppler echocardiograms, and (c) to investigate the ability of fosinopril to decrease platelet reactivity to physiological agonists. Biological and psychosocial risk factors for cardiovascular disorders (including CD4 count, viral load, antiretroviral medications, family history of cardiovascular disease, severity of addiction, depression, and subjective cardiovascular distress during cocaine use) will also be examined.