The goal of this study is to learn how injection drug use may affect the immune system.

The goal of this study is to learn how injection drug use may affect the immune system. One way to measure this is by looking at the blood and the gut, or gastrointestinal tract at the same time. It is thought that activating the immune system by injection drug use may increase destruction of immune cells in the gut. To test this theory, the investigators are enrolling HIV-negative injection drug users, HIV-negative people who do not use drugs and HIV-negative former injection drug users.

Inclusion Criteria:

• Ability to give informed consent
• Between the ages of 18 and 55
• Absence of medical conditions that would preclude flexible sigmoidoscopy
• Absence of active opportunistic infection requiring active therapy including antibiotics or anti-neoplastics (note this does not include prophylactic antibiotic therapy)

Exclusion Criteria:

• History of bleeding disorder
• Platelet count below 70,000
• INR>1.5 or PTT>2X control
• Active use of anticoagulants or aspirin therapy that cannot be interrupted
• Comorbid diagnosis of inflammatory bowel disease
• Pregnancy, incarceration, mentally disabled individuals
• HIV-1 infection
• Currently on Hepatitis C treatment

Group 1: HIV-uninfected, active IDU defined as a minimum of 3 injections of heroin per week (N=48)

Group 2: Non-injecting controls defined as no lifetime use of injection drugs and no illicit non-injection opiate or cocaine for at least 3 years (N=48)

Group 3: Former injectors of heroin with/without other agents will be recruited and followed after approximately 1 month (N=48) and 3 months (N=48) from the time of last injection.

All groups will be matched for age, sex, and race/ethnicity. Groups 1 and 3 will be matched for Hepatitis C status and HCV RNA levels. Group 1 subjects will be studied twice; at baseline, at 1-2 months to assess stability of findings. Group 2 will be studied once; Group 3 will be studied at 1 and 3 months after ceasing injections.