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).

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.

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

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.]