The Use of Leukapheresis to Support HIV Pathogenesis Studies

Study Overview
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Brief Summary
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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.

Official Title
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The Use of Leukapheresis to Support HIV Pathogenesis Studies

Conditions
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HIV

Intervention / Treatment
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* Procedure: Leukapheresis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Untreated non-controllers<br> | Procedure: Leukapheresis<br>* Blood will be taken by a needle placed in one arm and processed through a machine, which spins the blood so that the white blood cells will be separated out in the machine for purposes of this research and the rest of the blood will be returned through a needle in the other arm.<br>|
| Elite controllers<br> | Procedure: Leukapheresis<br>* Blood will be taken by a needle placed in one arm and processed through a machine, which spins the blood so that the white blood cells will be separated out in the machine for purposes of this research and the rest of the blood will be returned through a needle in the other arm.<br>|
| HAART-suppressed<br> | Procedure: Leukapheresis<br>* Blood will be taken by a needle placed in one arm and processed through a machine, which spins the blood so that the white blood cells will be separated out in the machine for purposes of this research and the rest of the blood will be returned through a needle in the other arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV DNA and RNA |  | Baseline and 6-12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, latent reservoir, functional cure, leukapheresis