Overview

Despite the dramatic improvements that have resulted from combination antiretroviral treatment, long-term efficacy, toxicity, cost, and the requirements for life-long adherence remain as formidable challenges. Also, there is emerging consensus that persistent HIV-associated disease occurs during long-term highly active antiretroviral therapy (HAART). This disease may be due to either direct drug-toxicity and/or persistent viral replication/production and/or persistent HIV-associated inflammation. Hence, strategies aimed at achieving complete viral eradication may be needed in order to fully restore health among HIV infected individuals. Even if complete eradication proves impossible-as most believe to be the case-a less rigorous but still desirable outcome might be achieving durable control of virus in the absence of therapy. That a "functional" cure is possible is well illustrated by those rare individuals who are able to durably control replication competent virus in the absence of therapy ("elite" controllers).

A more complete understanding of the relationship between inflammation and viral persistence is necessary before more rationale studies of HIV eradication can be designed. Also, a well validated high through-put virologic assay needs to be developed that can estimate the size of the latent reservoir. Since the level of replication competent virus in long-term treated patients (and in elite controllers) is very small (< 1% of CD4 cells harbor HIV), large numbers of CD4+ T cells most be obtained from study participants in order to routinely isolate and quantify virus persistence.

Eligibility

Inclusion Criteria:

• HIV seropositive
• Able to give informed consent
• Willing to undergo blood sampling and/or leukapheresis
• Meeting one of the following criteria: (1) on stable highly active antiretroviral therapy (HAART) with a recent undetectable viral load (< 50 copies/mL) ("HAART suppressed"), (2) antiretroviral untreated with an undetectable viral load (< 50 copies/mL) ("elite" controllers) and (3) antiretroviral untreated with a detectable viral load (> 1000 copies/mL) ("non-controllers")

Exclusion Criteria:

• Known anemia (HIV+ males Hct<34; females Hct<32) or contraindication to donating blood
• Blood coagulation disorder (including bleeding tendency or problems in past with blood clots)
• Platelets < 50,000/mm3
• PTT > 2x ULN
• INR > 1.5
• Albumin < 2.0 g/dL
• ALT > 5x ULN
• AST > 5x ULN
• Biopsy-proven or clinical diagnosis of cirrhosis
• Weight <120 lb
• High blood pressure > 160/100
• Low blood pressure < 100/70
• Pregnant