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When to Start Anti-HIV Drugs in Patients With Opportunistic Infections

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00055120
Recruitment Status : Completed
First Posted : February 20, 2003
Last Update Posted : October 15, 2014
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
The purpose of this study is to evaluate the effect of starting anti-HIV drugs in HIV infected patients who are being treated for opportunistic infections (OIs). This study will follow two patient groups: those who received anti-HIV drugs soon after being diagnosed with an OI and patients with OIs who deferred beginning anti-HIV drugs until after recovering from the OI.

Condition or disease Intervention/treatment Phase
HIV Infections AIDS-Related Opportunistic Infections Drug: Emtricitabine/tenofovir disoproxil fumarate Drug: Lopinavir/ritonavir Drug: Stavudine Phase 4

Detailed Description:

Despite the advent of highly active antiretroviral therapy (HAART), many HIV infected patients without access to antiretroviral therapy (ART) present with acute OIs. Such presentations pose a management problem, as there are currently no data available as to whether initiating HAART during the acute presentation is of benefit. Reports of an immune reconstitution inflammatory syndrome (IRIS) marked by increasing hypoxia or new pulmonary infiltrates have been associated with the initiation of ART in patients with AIDS. There is also concern as to drug interactions between ART and antimicrobials used to treat the presenting OI. This study will evaluate the possible benefits and costs of initiating ART in HIV infected patients who present with an AIDS-defining OI.

There are 2 steps in this study. In Step 1, patients will be randomly assigned to one of two study arms. Arm A will receive ART within 2 weeks of starting therapy for the acute OI. Arm B will have ART deferred until Step 2, at least 4 weeks and no more than 32 weeks after beginning therapy for the acute OI. Only Arm B participants will enter Step 2, which will likely begin between Weeks 6 and 12. The study will make the following drugs available for construction of an antiretroviral (ARV) regimen: emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), lopinavir/ritonavir (LPV/RTV), and stavudine (d4T). Use of other ARV drugs is at the discretion of the study official. Drug regimen additions and substitutions will be made on a case-by-case basis.

Patients will be followed for 48 weeks and will have 10 study visits. All study visits will include a physical exam, medication history, and blood collection. Patients will be asked to complete questionnaires assessing health status and adherence at selected visits.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 283 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Phase IV Study of Antiretroviral Therapy for HIV Infected Adults Presenting With Acute Opportunistic Infections: Immediate Versus Deferred Initiation of Antiretroviral Therapy
Study Start Date : March 2003
Actual Primary Completion Date : September 2006
Actual Study Completion Date : August 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Primary Outcome Measures :
  1. Survival, recurrence of presenting OI/bacterial infection (BI) or incidence of new AIDS-defining events, and HIV-1 plasma viral load at Week 48

Secondary Outcome Measures :
  1. HIV-1 plasma viral load at all timepoints up to and including Week 48
  2. CD4 counts at all timepoints up to and including Week 48
  3. changes in ARV regimen for lack of efficacy
  4. efficacy of treatment and clinical outcomes for specific OI/BI, including duration of and complications of treatment, incidence and duration of hospitalization, rate of relapse/recurrence, and incidence of IRIS and impact on outcomes in the two arms
  5. safety and tolerability, measured by Grade 3 and 4 signs and symptoms and laboratory toxicities, ART and OI/BI treatment changes and dose modifications due to toxicities, and IRIS
  6. HIV-1 drug resistance over time (genotype)
  7. health care resource use, including total inpatient days and emergency room visits compared in the two groups
  8. quality of life (QOL) and functional status outcomes, including overall self-reported QOL and functional status compared in the two groups at Week 48
  9. adherence, including self-reported adherence to all ARVs over the study period, examined for relationship with primary study outcomes, including death, progression, and viral suppression

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Note: Participants who enrolled in this study prior to Version 3.0 will be offered and allowed to switch to FTC/TDF if they wish. However, participants under the age of 18 cannot receive FTC/TDF through this study.

Inclusion Criteria for Step 1:

  • HIV-1 infected
  • Currently being treated for OI (including Pneumocystis carinii pneumonia [PCP]; cryptococcal meningitis; disseminated histoplasmosis; disseminated Mycobacterium avium complex [MAC]; cytomegalovirus [CMV] retinitis; CMV encephalitis; toxoplasmic encephalitis; other atypical non-tuberculous, non-MAC mycobacterial infections; or other serious, invasive BIs). Participants who have tuberculosis (TB) alone are ineligible for this study. Participants with bacterial pneumonia or serious BI must have a CD4 count less than 200 cells/mm3 within 30 days prior to study entry. Participants with other serious OIs, including other AIDS-defining and -related OIs for which appropriate therapy other than ART exists are eligible, pending investigator approval. Participants' current OI treatment must have been started within 14 days prior to study entry, but may have been discontinued prior to study entry.
  • Able to take oral medications
  • Parent or guardian willing to provide informed consent, if applicable
  • Willing to use acceptable methods of contraception

Exclusion Criteria for Step 1:

  • Any ART within 8 weeks prior to study entry
  • 31 or more days of any ARV within 6 months prior to entry
  • History of more than one virologic, immunologic, or clinical treatment failure while on a HAART regimen, or a history of more than one regimen change for unknown reasons
  • Systemic cancer chemotherapy within 30 days prior to study entry
  • Immunomodulators within 30 days prior to study entry, including growth factors, immune globulin, interleukins, and interferons (unless for hepatitis C virus or Kaposi's sarcoma)
  • Investigational ARV agents at study entry
  • Systemic investigational agents (except ARV drugs) within 30 days prior to study entry will be allowed at the study official's discretion
  • Anticipated use of certain medications
  • Kidney failure requiring dialysis
  • Current drug or alcohol use that, in the opinion of the study official, would interfere with the study
  • Treatment for current, first-treated, and diagnosed OI or BI for more than 14 days prior to study entry
  • Known resistance to ART that prohibits administration of an effective ART regimen
  • Current OI has recurred within 90 days prior to study entry. Recurrent BIs are not excluded.
  • Pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00055120

  Hide Study Locations
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United States, California
University of California, Davis Medical Center
Sacramento, California, United States, 95814
University of California, San Diego Antiviral Rese
San Diego, California, United States, 92103
San Francisco General Hospital
San Francisco, California, United States, 94110
San Mateo County AIDS Program
Stanford, California, United States, 94305-5107
Santa Clara Valley Medical Center
Stanford, California, United States, 94305-5107
Stanford Univ
Stanford, California, United States, 94305-5107
Willow Clinic
Stanford, California, United States, 94305-5107
Harbor General/UCLA
Torrance, California, United States, 90502-2052
United States, Colorado
University of Colorado Health Sciences Center, Denver
Denver, Colorado, United States, 80262-3706
United States, Florida
Univ of Miami
Miami, Florida, United States, 33136-1013
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30308
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611-3015
Cook County Hospital Core Center
Chicago, Illinois, United States, 60612
United States, Indiana
Methodist Hospital of Indiana
Indianapolis, Indiana, United States, 46202-1261
Indiana University Hosp
Indianapolis, Indiana, United States, 46202-5250
Wishard Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8106
United States, Massachusetts
Harvard (Massachusetts General Hospital)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Brigham and Womens Hospital
Boston, Massachusetts, United States, 02215
United States, Minnesota
Hennepin County Medical Clinic
Minneapolis, Minnesota, United States, 55455-0392
United States, Missouri
St. Louis Connect Care
St. Louis, Missouri, United States, 63108-2138
Washington University (St. Louis)
St. Louis, Missouri, United States, 63108-2138
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
New York, New York, United States, 10016-6481
Columbia University
New York, New York, United States, 10021
Community Health Network, Inc.
Rochester, New York, United States, 14642-0001
University of Rochester Medical Center
Rochester, New York, United States, 14642-0001
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27514
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0405
Case Western Reserve University
Cleveland, Ohio, United States, 44106-5083
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109-1998
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Presbyterian Medical Center - University of PA
Philadelphia, Pennsylvania, United States, 19104
University of Pennsylvania, Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02906
The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Tennessee
Comprehensive Care Clinic
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas, Southwestern Medical Center
Dallas, Texas, United States, 75235-9173
Univ of Texas, Galveston
Galveston, Texas, United States, 77555-0435
United States, Washington
University of Washington (Seattle)
Seattle, Washington, United States, 98104
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936-5067
South Africa
University of Witwatersrand
Parktown, Johannesburg, South Africa
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Study Chair: Andrew R. Zolopa, MD Division of Infectious Diseases, Stanford University

Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00055120     History of Changes
Other Study ID Numbers: ACTG A5164
First Posted: February 20, 2003    Key Record Dates
Last Update Posted: October 15, 2014
Last Verified: October 2014
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Anti-HIV Agents
Disease Progression
Drug Administration Schedule
Viral Load
Treatment Outcome
Survival Analysis
Treatment Naive
Additional relevant MeSH terms:
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Communicable Diseases
Opportunistic Infections
AIDS-Related Opportunistic Infections
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Parasitic Diseases
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors