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

This study has been completed.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001080
  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

MedlinePlus related topics:   AIDS    Flu   

Drug Information available for:   Lamivudine    Influenza Vaccines    Fluvirin    Heptavalent pneumococcal conjugate vaccine    Pneumococcal Vaccines   

U.S. FDA Resources

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

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

Estimated Enrollment:   20

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

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

Locations
United States, California
Univ of California / San Diego Treatment Ctr    
      San Diego, California, United States, 921036325
United States, Colorado
Univ of Colorado Health Sciences Ctr    
      Denver, Colorado, United States, 80262

Sponsors and Collaborators

Investigators
Study Chair:     Kuritzkes D    
Study Chair:     Richman D    
Study Chair:     Havlir D    
  More Information


Click here for more information about Lamivudine  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   ACTG 340
First Received:   November 2, 1999
Last Updated:   August 7, 2008
ClinicalTrials.gov Identifier:   NCT00001080
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

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Influenza, Human
Pneumonia, Pneumococcal
Lamivudine
Retroviridae Infections
Immunologic Deficiency Syndromes
Pneumonia

Additional relevant MeSH terms:
Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on December 03, 2008




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