study of the effectiveness of passive immunotherapy in hiv-infected patients who are in virologic failure

Conditions: HIV Infection

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.

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.

Eligibility criteria:
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

Keywords: hiv passive immunotherapy