Controlled Clinical Trial of Antiviral Cytotoxic T Lymphocyte (CTL) Infusion Following Combination Antiretroviral Drug Therapy for Asymptomatic HIV-1 Infection

Study Overview
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Brief Summary
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To evaluate the safety of anti-HIV CTL therapy in early stage patients and to verify the safety when combined with antiviral therapy with zidovudine/lamivudine/indinavir and low-dose interleukin-2 (IL-2). To compare the effects on plasma and cell-associated viral load following combination drug therapy with and without antiviral CTL in early-stage patients. To study in detail the immune effects of lowering viral burden with antiviral combination drugs with and without T cell infusion on antiviral CTL activity, viral suppression and proliferation, circulating T cell phenotype, T cell apoptosis, CD4 cell numbers, DTH reaction, and inflammatory cytokine levels. In an HIV-infected person, there is an ongoing struggle between HIV replication and host immune control. In the past decade most therapeutic strategies have targeted the virus. This approach has been frustrated by viral mutation to evade drug sensitivity. Promising drugs have recently been approved and there are encouraging sustained results from combination antiviral chemotherapy. However, even the most potent drug regimens do not seem to be curative, may eventually lead to drug resistance and may not completely restore lost immune function. The addition of immune-based therapy to antiviral drugs may lead to better viral control.

Detailed Description
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In an HIV-infected person, there is an ongoing struggle between HIV replication and host immune control. In the past decade most therapeutic strategies have targeted the virus. This approach has been frustrated by viral mutation to evade drug sensitivity. Promising drugs have recently been approved and there are encouraging sustained results from combination antiviral chemotherapy. However, even the most potent drug regimens do not seem to be curative, may eventually lead to drug resistance and may not completely restore lost immune function. The addition of immune-based therapy to antiviral drugs may lead to better viral control. This study has 2 regimens of 8 patients each. Patients are randomized as to CTL infusion only. Patients are stratified by viral load (less than 10,000 copies/ml vs. greater than or equal to 10,000 copies/ml). All patients receive combination drug therapy with AZT/3TC/indinavir for 9 months at which time patients have the option of continuing their study regimen another year or changing therapy. Patients in the T cell treatment regimen (regimen 2) receive 2 infusions of ex vivo expanded autologous anti-HIV CTL at 3 and 6 months after beginning AZT/3TC/indinavir therapy. The second infusion is administered with low-dose sc IL-2 1 day before and 4 days following T cell infusion.

Official Title
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Controlled Clinical Trial of Antiviral Cytotoxic T Lymphocyte (CTL) Infusion Following Combination Antiretroviral Drug Therapy for Asymptomatic HIV-1 Infection

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Indinavir sulfate
* Drug: Diphenhydramine hydrochloride
* Drug: Lymphocytes, Activated
* Drug: Lamivudine
* Drug: Zidovudine
* Drug: Acetaminophen
* Drug: Aldesleukin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients must have: Serologically confirmed HIV-1 infection. CD4 count >= 400/mm3. Exclusion Criteria Co-existing Condition: Patients with any of the following conditions or symptoms are excluded: Symptoms of HIV-1 disease, except lymphadenopathy. Symptoms of cardiac disease. Evidence of clinical pulmonary disease. Significant medical disease. Patients with any of the following prior conditions are excluded: History of symptoms of HIV-1 disease, except lymphadenopathy. Participation in another experimental AIDS treatment clinical trial within 4 weeks into entry. History of significant psychiatric disease. History of pancreatitis, history of neuropathy or neurotoxic drug therapy. History of serious allergies requiring either systemic steroid therapy or prior hospitalization. History of significant arrhythmia, infarction or heart failure. Immunomodulatory therapy such as steroids or cyclosporine, systemic chemotherapy or alpha-interferon. Prior Medication: Exclusion: Past treatment with any protease inhibitor. History of neurotoxic drug therapy. Risk Behavior: Excluded Patients with current substance abuse. Excessive alcohol intake.

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
Intervention Model: Parallel Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Indinavir sulfate|nan|
|Drug: Diphenhydramine hydrochloride|nan|
|Drug: Lymphocytes, Activated|nan|
|Drug: Lamivudine|nan|
|Drug: Zidovudine|nan|
|Drug: Acetaminophen|nan|
|Drug: Aldesleukin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy, Combination, Immunotherapy, Adoptive, T-Lymphocytes, Cytotoxic, Anti-HIV Agents, Viral Load