Using the Drug Thalidomide to Stimulate T Cells in HIV-Infected People

Study Overview
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Brief Summary
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Despite treatment with anti-HIV drugs, people infected with HIV continue to have problems with their immune systems. This study will evaluate whether the drug thalidomide, which stimulates the immune system's T cells, can improve immune system function in people with HIV.

Detailed Description
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In patients with chronic HIV infection, HIV replication and abnormalities in immune function persist following treatment with highly active antiretroviral therapy (HAART). Specifically, costimulatory T cell interactions are impaired. The immune modulatory drug thalidomide was recently found to costimulate T cells. Pharmacologic T cell costimulation may compensate for the T cell deficiencies in people with HIV disease and improve immune function. This study will test whether thalidomide treatment enhances HIV and cytomegalovirus (CMV)-specific immunity in patients with HIV and CMV, and will evaluate the effect of thalidomide on HIV replication. In this study, 40 HIV and CMV infected patients on HAART and 40 HIV uninfected CMV seropositive controls will be randomly assigned to low dose thalidomide or placebo treatment for 28 days. T cell responses and HIV replication and genetic diversification will be assessed.

Official Title
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Pharmacologic T Cell Costimulation In HIV Disease

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Thalidomide
* Drug: Thalidomide placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria HIV-infected for at least 5 years prior to study entry CD4 count of 300/mm3 or above Pre-HAART nadir CD4 count of 300/mm3 or less CMV infection HAART for 12 months prior to study entry Same effective HAART regimen for 3 months prior to study entry HIV viral load less than 200 copies/ml Clinically stable Exclusion Criteria Active opportunistic infection Females of childbearing potential

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive low dose thalidomide for 28 days | Drug: Thalidomide<br>* Tablet taken orally daily<br>|
| Placebo Comparator: 2<br>Participants will receive low dose thalidomide placebo for 28 days | Drug: Thalidomide placebo<br>* Placebo tablet taken orally daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Doubling in HIV Pol-specific CD8 cells, measured by ELISPOT |  | Through Day 28 | 
| Increase in CMV pp65 CD8 cells, measured by ELISPOT in the thalidomide treatment group |  | Throughout study | 
| Increase in HIV p24-specific IFN-gamma-secreting CD4 cells in the thalidomide treatment group, measured by fluorescence-activated cell sorting (FACS) |  | Throughout study | 
| Increase in cytomegalovirus (CMV)-specific interferon (IFN)-gamma-secreting CD4 T cells in the thalidomide treatment group, measured by FACS |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in the frequency of keyhole limpet hemocyanin (KLH)-specific lymphocyte proliferative responses in the thalidomide treatment group |  | Throughout study | 
| Increase in adverse events in the thalidomide treatment group |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune Modulation, Thalidomide, Immune reconstitution, Treatment Experienced