Potent Antiviral Therapy for Critically Ill HIV Infected Patients Admitted to Intensive Care

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00028327
First received: December 20, 2001
Last updated: February 28, 2011
Last verified: July 2004
  Purpose

Many HIV infected patients admitted to the intensive care area (ICA) have never taken anti-HIV drugs. The purpose of this study is to learn whether starting anti-HIV drugs while patients are in an ICA will help them to survive and get better faster. This study will also evaluate patients who, though not in an ICA, have been admitted to the hospital for serious illnesses or infections.


Condition Intervention Phase
HIV Infections
Drug: Lamivudine/Zidovudine
Drug: Nelfinavir mesylate
Drug: Efavirenz
Drug: Lamivudine
Drug: Zidovudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Study to Evaluate Immediate Potent Antiretroviral Therapy for HIV-Infected Subjects With CD4 Cell Counts Less Than 350 Cells/mm3 Admitted to Intensive Care Areas With an AIDS-Defining Illness, Pneumonia, or Sepsis

Resource links provided by NLM:


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

Estimated Enrollment: 250
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Detailed Description:

There has been considerable debate over the management of HIV infected individuals admitted to the ICA. Mortality in HIV infected patients in the ICA correlates with the level of immune suppression. The majority of HIV infected individuals entering the ICA are antiretroviral naive. Despite the high mortality rates and the opportunity to intervene with antiretroviral therapy, physicians do not routinely administer highly active antiretroviral therapy (HAART) in the ICA. Early initiation of HAART, which improves immune function, could potentially reduce mortality. Numerous studies have shown that there is a dramatic drop in the HIV-1 RNA levels accompanied by an increase in the CD4 cell count within the first 2 to 4 weeks of therapy. Sufficient data now exist that antiretrovirals could be administered in the ICA with careful monitoring and attention to drug interactions. This study will evaluate the effect of HAART in patients admitted to the hospital with an AIDS-defining illness, pneumonia, or sepsis.

Upon entry into the study, patients are stratified according to a severity of illness score (SAPS I) and CD4 cell count. Patients then are assigned to 1 of 2 study arms: Arm A: HAART (lamivudine [3TC] and zidovudine [ZDV], or 3TC/ZDV, and nelfinavir [NFV] and efavirenz [EFV]); or an alternative HAART for 4 weeks. Arm B: No antiretroviral regimen. Evaluations of the following are performed: drug toxicity, immune status, viral load, arterial blood gas, ventilator parameters, and evolution of the presenting illness. Pharmacokinetic trough concentration analyses are performed on all patients in Arm A during 3 time points of their illness. Patients are followed for 24 weeks after entry. Patients in Arm A may elect to participate in two substudies. The first substudy will measure efavirenz and nelfinavir drug levels in the blood to determine how critical illness affects pharmacokinetics. The second substudy will evaluate the benefit of HAART in HIV infected patients being treated for pneumocystis carinii pneumonia.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • HIV-1 infection
  • CD4 cell count less than 350 cells/mm3 within 120 hours prior to study entry
  • Admission to an ICA (or to any part of the hospital with an arterial blood gas PaO2/FiO2 ratio of < 200 or SAPS I score > 13) within 120 hours prior to study entry
  • Admitted to the hospital for sepsis, pneumonia, or other AIDS-defining disease
  • Acceptable methods of contraception

Exclusion Criteria

  • Known resistance or intolerance to antiretroviral drugs that precludes use of an effective HAART regimen of FDA approved drugs, excluding abacavir or full-dose ritonavir
  • More than 7 days of HAART (a regimen of at least 3 drugs that includes a protease inhibitor, a nonnucleoside reverse transcriptase inhibitor, or three nucleoside analogues) within 4 weeks prior to study entry
  • Investigational drug within 14 days prior to study entry
  • Pregnant or breast-feeding
  • Allergy or sensitivity to any of the study drugs that cannot be substituted with another drug
  • CNS mass lesion or bacterial meningitis
  • Certain medications
  • Uncertain availability for 6 month course of study
  • Require regular stomach suctioning
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00028327

Locations
United States, California
Univ of Southern California
Los Angeles, California, United States, 90033-1079
Univ of California, San Diego
San Diego, California, United States, 92103
Univ of California San Francisco
San Francisco, California, United States, 94110
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington Univ School of Medicine
St Louis, Missouri, United States, 63108
United States, New York
Beth Israel Med Ctr
New York, New York, United States, 10003
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Diane Havlir
Study Chair: Denis Jones
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00028327     History of Changes
Other Study ID Numbers: ACTG A5141, AACTG A5141, A5161s, A5162s
Study First Received: December 20, 2001
Last Updated: February 28, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Zidovudine
HIV Protease Inhibitors
CD4 Lymphocyte Count
Lamivudine
Pneumonia
Nelfinavir
Reverse Transcriptase Inhibitors
Antiretroviral Therapy, Highly Active
Efavirenz
Intensive Care Units
Sepsis

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
Zidovudine
Lamivudine
Reverse Transcriptase Inhibitors
Efavirenz
Lamivudine, zidovudine drug combination
Nelfinavir
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on April 23, 2014