Study of the Effectiveness of Passive Immunotherapy in HIV-Infected Patients Who Are in Virologic Failure

Study Overview
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Brief Summary
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To study the effect of passive immunotherapy (PIT) over the HIV-viral load and the CD4 T+-cell counts in patients who have failed to respond to three different Highly-Active Antiretroviral Therapy (HAART), and who have at the moment less than 100 CD4+-T cells/ml and a viral load over 20,000 copies/ml.

Detailed Description
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Double blind comparative randomized study with placebo in two phases: Phase I: I: A pilot study to asses the virologic efficacy in 30 patients will be done. They will be under the same HAART regimen, and they will be randomized to receive: Group I: HAART + PIT (n= 15) Group II: HAART + placebo (non-hyperimmune plasma) (n= 15) Passive immunotherapy will consist in 500 cc of inactivated plasma with methylene-blue (standard inactivation method) from asymptomatic patients in early phases of the infection. A transfusion will be done, and a complete blood test including viral load and CD4+-T cell counts will be done at days 3, 7, 14, 21 and 28. The non-hyperimmune plasma (Group II) will be inactivated by the same method. A second dose of hyperimmune plasma and placebo (Group I and Group II respectively) will be administered at +1 month from the beginning of the trial. A complete blood test including viral load and CD4+-T cell counts will be done at month +2, +3 and +4. Phase II: 30 patients under the same HAART regimen will be randomized to receive: Group I: HAART + PIT (n= 15) Group II: HAART + placebo (non-hyperimmune plasma) (n= 15) Passive immunotherapy will consist in 500 cc of inactivated plasma with methylene-blue (standard inactivation method) from asymptomatic patients in early phases of the infection, guided by the neutralization capacity of the plasma donors over the virus' receptor . A transfusion will be done, and a complete blood test including viral load and CD4+-T cell counts will be done at days 3, 7, 14, 21 and 28. The non-hyperimmune plasma (Group II) will be inactivated by the same method. A second dose of hyperimmune plasma and placebo (Group I and Group II respectively) will be administered at +1 month from the beginning of the phase II. The patients will remain under HAART the next year. A complete clinical examination, and a blood test that includes hemogram and biochemical parameters (renal and hepatic function), and viral load will be done each month. Every three months, a CD4+/CD8+ T cell count will be done, and it will be obtained plasma and serum from each patient. Additionally, a genotype and a virtual phenotype of the HIV will be obtained at the beginning and at the end of the study. Study end-points: -Main end-point: Phase I: proportion of patients who reduce their plasma viral load > or = 1 log after two infusions of hyperimmune plasma. Phase II: proportion of patients who reduce their plasma viral load > or = 1 log after a year. - Secondary end-points: Proportion of patients whose CD4+ T cell count is over 100 cells/mm3 after a year. Proportion of patients whose p24-antigenemia is below the limits of detection. Number of mutations conferring resistance to antiretrovirals at the end of the study compared to the mutations at the beginning. Type C events. Death. Toxicity. Adherence.

Official Title
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Passive Immunotherapy in HIV-Infected Patients Who Fail to Respond to Multiple Highly Active Antiretroviral Treatment. Randomized Study in Two Phases.

Conditions
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HIV Infection

Intervention / Treatment
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* Procedure: Plasma infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected patients (CDC C category) confirmed by a Western-blot CD4 T cell count under 100/ml form 6 months before the inclusion, and who have never been over 600 CD4 T cells/ml in the last 6 months, even if they have been receiving HAART. The patients have received at least 3 different HAART regimens, and they have failed to respond (define failure: CD4 T cell count under 100/ml and plasma viral load over 20,000 copies/ml). Plasma viral load over 20,000 copies/ml during at least 6 months. Written informed consent 18 years old or older Exclusion Criteria: Asymptomatic patients who fill the A category of the CDC (1993) Younger than 18 years old Who are not expected to accomplish the treatment or the follow up visits Pregnancy, breast-feeding women, or women who want to get pregnant Denied consent

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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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Plasma infusion|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lowering of plasma viral load after the first plasma infusion |  |  | 
| Lowering of plasma viral load after a year |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elevation of CD4 T cell count |  |  | 
| Negativation of p24 HIV antigen |  |  | 
| HIV RNA mutations conferring resistance to HAART |  |  | 
| Development of C-events |  |  | 
| Dead |  |  | 
| Toxicity |  |  | 
| Accomplishment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Passive immunotherapy