Clinical trial NCT00001080: Effect of Vaccination on Turnover of Lamivudine (3TC) Sensitive and Resistant Virus Populations in HIV-1-Infected Individuals
Official title: Effect of Vaccination on Turnover of Lamivudine (3TC) Sensitive and Resistant Virus Populations in HIV-1-Infected Individuals
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: HIV Infections
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
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.\]

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
name: Kuritzkes D
role: STUDY_CHAIR
name: Richman D
role: STUDY_CHAIR
name: Havlir D
role: STUDY_CHAIR
References: