Study of the Effectiveness of Passive Immunotherapy in HIV-Infected Patients Who Are in Virologic Failure
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
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:
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Group I: HAART + PIT (n= 15)
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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:
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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:
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Proportion of patients whose CD4+ T cell count is over 100 cells/mm3 after a year.
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Proportion of patients whose p24-antigenemia is below the limits of detection.
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Number of mutations conferring resistance to antiretrovirals at the end of the study compared to the mutations at the beginning.
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Type C events.
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Death.
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Toxicity.
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Adherence.
Study Design
Outcome Measures
Primary Outcome Measures
- Lowering of plasma viral load after the first plasma infusion []
- Lowering of plasma viral load after a year []
Secondary Outcome Measures
- 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 []
Eligibility Criteria
Criteria
Inclusion Criteria:
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HIV-1 infected patients (CDC C category) confirmed by a Western-blot
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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.
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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).
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Plasma viral load over 20,000 copies/ml during at least 6 months.
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Written informed consent
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18 years old or older
Exclusion Criteria:
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Asymptomatic patients who fill the A category of the CDC (1993)
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Younger than 18 years old
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Who are not expected to accomplish the treatment or the follow up visits
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Pregnancy, breast-feeding women, or women who want to get pregnant
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Denied consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Clínic Barcelona | Barcelona | Spain | 08036 |
Sponsors and Collaborators
- Hospital Clinic of Barcelona
Investigators
- Principal Investigator: Felipe Garcia, MD, PhD, Hospital Clinic of Barcelona
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PIT-01