Effect of Vaccination on Turnover of Lamivudine (3TC) Sensitive and Resistant Virus Populations in HIV-1-Infected Individuals
试验速览
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Concurrent Medication:
- •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/mm
- •One plasma HIV-1 RNA level between >= 20,000 and < 120,000 copies/ml.
- •Prior Medication:
- •Stable antiretroviral therapy.
排除标准
- •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:
- •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:
- •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:
- •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.]