Effect of Vaccination on Turnover of Lamivudine (3TC) Sensitive and Resistant Virus Populations in HIV-1-Infected Individuals
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About
To ascertain whether the origin of plasma HIV-1-RNA following T cell activation represents the activation of latently infected cells or an increase in cells permissive for replacing viral mutants.
The mechanism by which immune stimulation increases circulating levels of HIV-1 is not known. In particular, it is uncertain whether the transient increase in plasma HIV-1 RNA is due to enhanced replication of an actively replicating pool of HIV-1, or is due instead to activation of proviral sequences in previously resting CD4+ cells. One approach to discriminate these alternatives is a "molecular pulse-chase" experiment. In this approach, drug resistant mutants would be selected by administration of Lamivudine (3TC).
Full description
The mechanism by which immune stimulation increases circulating levels of HIV-1 is not known. In particular, it is uncertain whether the transient increase in plasma HIV-1 RNA is due to enhanced replication of an actively replicating pool of HIV-1, or is due instead to activation of proviral sequences in previously resting CD4+ cells. One approach to discriminate these alternatives is a "molecular pulse-chase" experiment. In this approach, drug resistant mutants would be selected by administration of Lamivudine (3TC).
Twenty subjects without prior 3TC experience will be treated with 3TC for 2 weeks. On day 14, half of the subjects will receive immunization with both the influenza and pneumococcal vaccine. 3TC will be discontinued at this time. Patients will be followed for 4 weeks after the immunization.
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Inclusion and exclusion criteria
Inclusion Criteria
Concurrent Medication:
Allowed:
- Antiretroviral therapy, provided the patient has been on the same dose and drugs for 60 days prior to study entry.
Patients must have:
- Documented HIV infection.
- CD4 lymphocyte count of > 300 cells/mm3.
- One plasma HIV-1 RNA level between >= 20,000 and < 120,000 copies/ml.
Prior Medication:
Allowed:
- Stable antiretroviral therapy.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms and conditions are excluded:
- Presence of an AIDS defining opportunistic infection, including Kaposi's sarcoma.
- Allergy to influenza or pneumococcal vaccine or their components; to egg or egg products.
- Unexplained temperature >= 38.5 degrees C for 7 consecutive days within the 30 days prior to study entry.
- Concurrent participation in other experimental therapies.
Concurrent Medication:
Excluded:
- Systemic chemotherapy.
- Steroids.
- Corticosteroids.
- Vaccinations.
- Any new antiretroviral agents that the patient was not taking at the time of study entry and not prescribed by the study.
- Colony stimulating factors including G-CSF or rEPO.
- Immune modulators/immune based therapies.
Concurrent Treatment:
Excluded:
- Radiation therapy.
- Transfusion dependent patients.
Patients with any of the following prior conditions are excluded:
- History of an AIDS defining opportunistic infection, including Kaposi's sarcoma (except limited cutaneous diseases [< 5 lesions]).
- History of acute or chronic pancreatitis.
Prior Medication:
Excluded:
- Prior treatment with 3TC.
Excluded within 30 days of study entry:
- Treatment with immune modulators.
- Acute or chronic therapy for recognized infections (eg, influenza, HSV, VZV).
Excluded within 1 year of study entry:
Treatment with an influenza and/or pneumonia vaccine
[AS PER AMENDMENT 1/23/97:
- influenza vaccine only].
[AS PER AMENDMENT 1/23/97:
- Excluded within 3 years of study entry:
- Pneumonia vaccine.]
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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