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

A Phase IV Study of Antiretroviral Therapy for HIV Infected Adults Presenting With Acute Opportunistic Infections: Immediate Versus Deferred Initiation of Antiretroviral Therapy


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

Source 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.

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.

Overall Status Completed
Start Date March 2003
Completion Date August 2007
Primary Completion Date September 2006
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
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
Measure Time Frame
HIV-1 plasma viral load at all timepoints up to and including Week 48
CD4 counts at all timepoints up to and including Week 48
changes in ARV regimen for lack of efficacy
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
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
HIV-1 drug resistance over time (genotype)
health care resource use, including total inpatient days and emergency room visits compared in the two groups
quality of life (QOL) and functional status outcomes, including overall self-reported QOL and functional status compared in the two groups at Week 48
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
Enrollment 283

Intervention Type: Drug

Intervention Name: Emtricitabine/tenofovir disoproxil fumarate

Intervention Type: Drug

Intervention Name: Lopinavir/ritonavir

Intervention Type: Drug

Intervention Name: Stavudine



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

Gender: All

Minimum Age: 13 Years

Maximum Age: N/A

Healthy Volunteers: No

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

Puerto Rico

South Africa

United States

Verification Date

October 2014

Has Expanded Access No
Condition Browse
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Diagnostic

Masking: None (Open Label)

Source: ClinicalTrials.gov