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

This study has been withdrawn prior to enrollment.
(as of 4/23/97)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001080
First received: November 2, 1999
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

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).


Condition Intervention
HIV Infections
Biological: Influenza Virus Vaccine
Biological: Pneumococcal Vaccine, Polyvalent (23-valent)
Drug: Lamivudine

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Effect of Vaccination on Turnover of Lamivudine (3TC) Sensitive and Resistant Virus Populations in HIV-1-Infected Individuals

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Enrollment: 0
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.]
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001080

Sponsors and Collaborators
Investigators
Study Chair: Kuritzkes D
Study Chair: Richman D
Study Chair: Havlir D
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001080     History of Changes
Other Study ID Numbers: ACTG 340, 11311
Study First Received: November 2, 1999
Last Updated: May 1, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lamivudine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on October 01, 2014