Effect of Vaccination on Turnover of Lamivudine (3TC) Sensitive and Resistant Virus Populations in HIV-1-Infected Individuals

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Vaccination on Turnover of Lamivudine (3TC) Sensitive and Resistant Virus Populations in HIV-1-Infected Individuals

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Influenza Virus Vaccine
* Biological: Pneumococcal Vaccine, Polyvalent (23-valent)
* Drug: Lamivudine


Participation Criteria
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Eligibility Criteria
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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.]

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 |
| --- |
|Biological: Influenza Virus Vaccine|nan|
|Biological: Pneumococcal Vaccine, Polyvalent (23-valent)|nan|
|Drug: Lamivudine|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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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