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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00055120
• Other study ID #: ACTG A5164
• Secondary ID: DAIDS-ES ID 1000
• Status: Completed
• Phase: Phase 4
• First received: February 19, 2003
• Last updated: October 14, 2014
• Start date: March 2003
• Est. completion date: August 2007

Study information

• Verified date: October 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 283
• Est. completion date: August 2007
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• AIDS-Related Opportunistic Infections
• Communicable Diseases
• HIV Infections
• Infection
• Opportunistic Infections

Intervention

Drug:
• Emtricitabine/tenofovir disoproxil fumarate

• Lopinavir/ritonavir

• Stavudine

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico	San Juan
South Africa	University of Witwatersrand	Parktown	Johannesburg
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland, Institute of Human Virology	Baltimore	Maryland
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Harvard (Massachusetts General Hospital)	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Cook County Hospital Core Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
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	University of Texas, Southwestern Medical Center	Dallas	Texas
United States	University of Colorado Health Sciences Center, Denver	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Univ of Texas, Galveston	Galveston	Texas
United States	Indiana University Hosp	Indianapolis	Indiana
United States	Methodist Hospital of Indiana	Indianapolis	Indiana
United States	Wishard Hospital	Indianapolis	Indiana
United States	Univ of Miami	Miami	Florida
United States	Hennepin County Medical Clinic	Minneapolis	Minnesota
United States	Comprehensive Care Clinic	Nashville	Tennessee
United States	Beth Israel Medical Center	New York	New York
United States	Columbia University	New York	New York
United States	NYU/Bellevue	New York	New York
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	Community Health Network, Inc.	Rochester	New York
United States	University of Rochester Medical Center	Rochester	New York
United States	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	University of Washington (Seattle)	Seattle	Washington
United States	St. Louis Connect Care	St. Louis	Missouri
United States	Washington University (St. Louis)	St. Louis	Missouri
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

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico,  South Africa, 

References & Publications (5)

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. — View Citation

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.

Núñez M, Asencio R, Valencia ME, Leal M, González-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. — View Citation

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 analys — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	HIV-1 plasma viral load at all timepoints up to and including Week 48
Secondary	CD4 counts at all timepoints up to and including Week 48
Secondary	changes in ARV regimen for lack of efficacy
Secondary	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
Secondary	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
Secondary	HIV-1 drug resistance over time (genotype)
Secondary	health care resource use, including total inpatient days and emergency room visits compared in the two groups
Secondary	quality of life (QOL) and functional status outcomes, including overall self-reported QOL and functional status compared in the two groups at Week 48
Secondary	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

External Links

•   Click here for more information on emtricitabine/tenofovir disoproxil fumarate
•   Click here for more information on lopinavir/ritonavir
•   Click here for more information on stavudine
•   Haga clic aquí para ver información sobre este ensayo clínico en español.