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

NCT ID: NCT00055120

Last Updated: 2014-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 283 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-03-31
• Study Completion Date: 2007-08-31

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.

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.

Conditions

HIV Infections; AIDS-Related Opportunistic Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Interventions

Emtricitabine/tenofovir disoproxil fumarate

Intervention Type: DRUG

Lopinavir/ritonavir

Intervention Type: DRUG

Stavudine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Principal Investigators

Andrew R. Zolopa, MD

Role: STUDY_CHAIR

Division of Infectious Diseases, Stanford University

Locations

University of California, Davis Medical Center

Sacramento, California, United States

University of California, San Diego Antiviral Rese

San Diego, California, United States

San Francisco General Hospital

San Francisco, California, United States

San Mateo County AIDS Program

Stanford, California, United States

Santa Clara Valley Medical Center

Stanford, California, United States

Stanford Univ

Stanford, California, United States

Willow Clinic

Stanford, California, United States

Harbor General/UCLA

Torrance, California, United States

University of Colorado Health Sciences Center, Denver

Denver, Colorado, United States

Univ of Miami

Miami, Florida, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Cook County Hospital Core Center

Chicago, Illinois, United States

Methodist Hospital of Indiana

Indianapolis, Indiana, United States

Indiana University Hosp

Indianapolis, Indiana, United States

Wishard Hospital

Indianapolis, Indiana, United States

University of Maryland, Institute of Human Virology

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Harvard (Massachusetts General Hospital)

Boston, Massachusetts, United States

Beth Israel Deaconess - West Campus

Boston, Massachusetts, United States

Brigham and Womens Hospital

Boston, Massachusetts, United States

Hennepin County Medical Clinic

Minneapolis, Minnesota, United States

St. Louis Connect Care

St Louis, Missouri, United States

Washington University (St. Louis)

St Louis, Missouri, United States

Beth Israel Medical Center

New York, New York, United States

NYU/Bellevue

New York, New York, United States

Columbia University

New York, New York, United States

Community Health Network, Inc.

Rochester, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Presbyterian Medical Center - University of PA

Philadelphia, Pennsylvania, United States

University of Pennsylvania, Philadelphia

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

The Miriam Hospital

Providence, Rhode Island, United States

Comprehensive Care Clinic

Nashville, Tennessee, United States

University of Texas, Southwestern Medical Center

Dallas, Texas, United States

Univ of Texas, Galveston

Galveston, Texas, United States

University of Washington (Seattle)

Seattle, Washington, United States

University of Puerto Rico

San Juan, , Puerto Rico

University of Witwatersrand

Parktown, Johannesburg, South Africa

Countries

United States; Puerto Rico; South Africa

References

Wislez M, Bergot E, Antoine M, Parrot A, Carette MF, Mayaud C, Cadranel J. Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia. Am J Respir Crit Care Med. 2001 Sep 1;164(5):847-51. doi: 10.1164/ajrccm.164.5.2007034.

Reference Type: BACKGROUND

PMID: 11549544 (View on PubMed)

Bartlett JA, DeMasi R, Quinn J, Moxham C, Rousseau F. Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS. 2001 Jul 27;15(11):1369-77. doi: 10.1097/00002030-200107270-00006.

Reference Type: BACKGROUND

PMID: 11504958 (View on PubMed)

Hamill RJ. Immune restoration syndrome in AIDS and mycoses. Program and abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, IL. Abtract 1272.

Reference Type: BACKGROUND

Nunez M, Asencio R, Valencia ME, Leal M, Gonzalez-Lahoz J, Soriano V. Rate, causes, and clinical implications of presenting with low CD4+ cell counts in the era of highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2003 May;19(5):363-8. doi: 10.1089/088922203765551719.

Reference Type: BACKGROUND

PMID: 12803995 (View on PubMed)

Sax PE, Sloan CE, Schackman BR, Grant PM, Rong J, Zolopa AR, Powderly W, Losina E, Freedberg KA; Cepac US And Actg A5164 Investigators. Early antiretroviral therapy for patients with acute aids-related opportunistic infections: a cost-effectiveness analysis of ACTG A5164. HIV Clin Trials. 2010 Sep-Oct;11(5):248-59. doi: 10.1310/hct1105-248.

Reference Type: RESULT

PMID: 21126955 (View on PubMed)

Grant PM, Komarow L, Andersen J, Sereti I, Pahwa S, Lederman MM, Eron J, Sanne I, Powderly W, Hogg E, Suckow C, Zolopa A. Risk factor analyses for immune reconstitution inflammatory syndrome in a randomized study of early vs. deferred ART during an opportunistic infection. PLoS One. 2010 Jul 1;5(7):e11416. doi: 10.1371/journal.pone.0011416.

Reference Type: DERIVED

PMID: 20617176 (View on PubMed)

Zolopa A, Andersen J, Powderly W, Sanchez A, Sanne I, Suckow C, Hogg E, Komarow L. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One. 2009;4(5):e5575. doi: 10.1371/journal.pone.0005575. Epub 2009 May 18.

Reference Type: DERIVED

PMID: 19440326 (View on PubMed)

Other Identifiers

DAIDS-ES ID 10005

Identifier Type: -

Identifier Source: secondary_id

ACTG A5164

Identifier Type: -

Identifier Source: org_study_id