Study of the Effectiveness of Passive Immunotherapy in HIV-Infected Patients Who Are in Virologic Failure
- Conditions
- HIV Infection
- Registration Number
- NCT00353327
- Lead Sponsor
- Hospital Clinic of Barcelona
- 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.
- 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:
1. Group I: HAART + PIT (n= 15)
2. 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:
1. Group I: HAART + PIT (n= 15)
2. 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:
1. Proportion of patients whose CD4+ T cell count is over 100 cells/mm3 after a year.
2. Proportion of patients whose p24-antigenemia is below the limits of detection.
3. Number of mutations conferring resistance to antiretrovirals at the end of the study compared to the mutations at the beginning.
4. Type C events.
5. Death.
6. Toxicity.
7. Adherence.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 30
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Lowering of plasma viral load after the first plasma infusion Lowering of plasma viral load after a year
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
Hospital Clínic Barcelona
🇪🇸Barcelona, Spain