HIV Infections
Conditions
Keywords
Lymphocyte Transformation, HIV-1, Drug Resistance, Microbial, CD4-Positive T-Lymphocytes, Lamivudine, Influenza Vaccine, RNA, Viral, Bacterial Vaccines, Anti-HIV Agents, Pneumonia, Pneumococcal, Viral Load
Brief summary
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).
Detailed 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.
Interventions
BIOLOGICALInfluenza Virus Vaccine
DRUGLamivudine
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[AS PER AMENDMENT 1/23/97: * influenza vaccine only\]. \[AS PER AMENDMENT 1/23/97: * Excluded within 3 years of study entry: * Pneumonia vaccine.\]
Outcome results
None listed