Controlled Clinical Trial of Antiviral Cytotoxic T Lymphocyte (CTL) Infusion Following Combination Antiretroviral Drug Therapy for Asymptomatic HIV-1 Infection
| Status: | Terminated |
|---|---|
| Conditions: | Infectious Disease, HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/15/2016 |
| End Date: | April 2003 |
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.
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.
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.
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.
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.
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