effect of vaccination on turnover of lamivudine (3tc) sensitive and resistant virus populations in hiv-1-infected individuals

Conditions: HIV Infections

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).

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.

Eligibility 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 \[as per amendment 1/23/97: * influenza vaccine only\]. \[as per amendment 1/23/97: * excluded within 3 years of study entry: * pneumonia vaccine.\]

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