A Study on the Rate of Opportunistic (AIDS-Related) Infections Among HIV-Positive Children Who Have Stopped Taking Their OI Preventive Medications

NCT ID: NCT00001078

Last Updated: 2011-03-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL

Brief Summary

The purpose of this study is to find out if it is safe for HIV-positive children who are responding well to their anti-HIV treatment to stop taking medications that prevent AIDS-related infections (opportunistic infections) such as pneumonia and other bacterial infections. This is an observational study, meaning children will only be monitored to see if they develop any infections.

Children have been receiving medications to prevent complications of HIV infection, such as Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC) disease, or other bacterial infections. It is common for HIV-positive patients with low CD4 counts to receive these preventive medications. However, these drugs can have serious side effects, they are expensive, and it is possible for bacteria resistant to the drugs to grow. For these reasons, it may be beneficial to the child to stop taking these preventive medications if he/she has been on anti-HIV (antiretroviral) therapy and has improved CD4 counts. This study will look at how many children who stop taking their medications develop opportunistic infections.

Detailed Description

Due to the strong correlation between a significant decrease in CD4 count and the frequency and magnitude of OIs such as Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and severe bacterial infections, CD4 count has become the major criterion for initiating antimicrobial prophylaxis for OIs. However, despite the benefits of these antimicrobial drugs, all are associated with adverse side effects, and patients with reconstituted immune systems following antiretroviral therapy may be receiving prophylaxis unnecessarily. Benefits to stopping prophylaxis include: (1) elimination of adverse effects from drugs; (2) reduction in drug costs; and (3) removal of selective pressure for the development of drug-resistant microbes. These benefits must be weighed against the disadvantages, however, such as more frequent determinations of CD4 counts to assure maintenance of immunocompetence, more frequent occurrence of serious OIs otherwise preventable with prophylaxis in patients lost to follow-up, and possible occurrence of atypical PCP because of prior exposure to anti-PCP drugs. [AS PER AMENDMENT 04/26/02: The extent of complete immune restitution has not yet been defined. An important corollary of an incomplete immune recovery is that vaccination schedules might need to be adjusted to obtain optimal responses in HIV-infected patients on highly active antiretroviral therapy (HAART). Therefore, a third dose of hepatitis A virus vaccine will be administered.]

After pre-entry and entry laboratory studies, patients are followed every 8 weeks until the last patient has completed 104 weeks of study observation. Hepatitis A vaccination is administered at entry and Week 24 to measure responses to neoantigen. [AS PER AMENDMENT 04/26/02: All patients (except those co-enrolled in P1024 on or after November 1, 2001) who have received 2 doses of hepatitis A virus vaccine during the study will be offered an opportunity to enroll in Step II of P1008. Patients in Step II receive a third dose of hepatitis A vaccination at Week 104 or later. Additional blood samples are taken 8 weeks later for antibody detection and peripheral blood mononuclear cell (PBMC) cryopreservation.] All serious bacterial infections that are Grade 3 or higher and OI events are recorded and compared to historical event rates. Virologic and immunologic marker studies are done in all patients and correlated with the risk of developing serious bacterial infections or OI events. Patients are considered to have reached an endpoint if they develop PCP, 2 serious bacterial infections, other Category C OI diagnoses, or CD4% less than 15% and re-initiation of PCP prophylaxis.

Conditions

HIV Infections

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Hepatitis A Vaccine (Inactivated)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

Children may be eligible for this study if they:

• Are HIV-positive.
• Have a CD4 percent greater than or equal to 25 percent if they are under 6 years of age, or have a CD4 percent greater than or equal to 20 percent on 2 occasions if they are between the ages of 6 and 21.
• Have been receiving preventive treatment for PCP for at least 6 months and have not stopped treatment for more than 3 months before study entry.
• Are willing to stop taking preventive treatment for PCP and MAC.
• Have received the same continuous antiretroviral (anti-HIV) therapy for the 16 weeks before beginning the study. (Continuous therapy means missing no more than a total of 3 weeks during the 16 weeks.)
• Are between the ages of 2 and 21 years (consent of parent or guardian is required if under 18).

Exclusion Criteria

Children will not be eligible for this study if they:

• Have PCP.
• Have any other active infection, such as tuberculosis or toxoplasmosis, or any other significant disease.
• Are receiving chemotherapy for cancer or certain other medications.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Principal Investigators

Wayne Dankner

Role: STUDY_CHAIR

Ram Yogev

Role: STUDY_CHAIR

Walter Hughes

Role: STUDY_CHAIR

Locations

Univ of Alabama at Birmingham - Pediatric

Birmingham, Alabama, United States

Phoenix Childrens Hosp

Phoenix, Arizona, United States

UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, United States

Long Beach Memorial (Pediatric)

Long Beach, California, United States

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, United States

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, United States

Children's Hosp of Oakland

Oakland, California, United States

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, United States

Children's Hosp of Denver

Denver, Colorado, United States

Yale Univ Med School

New Haven, Connecticut, United States

Children's Hosp of Washington DC

Washington D.C., District of Columbia, United States

Howard Univ Hosp

Washington D.C., District of Columbia, United States

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Univ of Miami (Pediatric)

Miami, Florida, United States

Palm Beach County Health Dept

Riviera Beach, Florida, United States

Emory Univ Hosp / Pediatrics

Atlanta, Georgia, United States

Cook County Hosp

Chicago, Illinois, United States

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, United States

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, United States

Children's Hosp of Boston

Boston, Massachusetts, United States

Boston City Hosp / Pediatrics

Boston, Massachusetts, United States

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Univ of Massachusetts Med School

Worcester, Massachusetts, United States

Children's Hosp of Michigan

Detroit, Michigan, United States

Univ of Mississippi Med Ctr

Jackson, Mississippi, United States

UMDNJ - Robert Wood Johnson Med School / Pediatrics

New Brunswick, New Jersey, United States

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl

Newark, New Jersey, United States

SUNY - Brooklyn

Brooklyn, New York, United States

North Shore Univ Hosp

Great Neck, New York, United States

Schneider Children's Hosp

New Hyde Park, New York, United States

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Metropolitan Hosp Ctr

New York, New York, United States

Columbia Presbyterian Med Ctr

New York, New York, United States

Harlem Hosp Ctr

New York, New York, United States

Univ of Rochester Med Ctr

Rochester, New York, United States

State Univ of New York at Stony Brook

Stony Brook, New York, United States

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, United States

Duke Univ Med Ctr

Durham, North Carolina, United States

Columbus Children's Hosp

Columbus, Ohio, United States

Children's Hosp of Philadelphia

Philadelphia, Pennsylvania, United States

Med Univ of South Carolina

Charleston, South Carolina, United States

Med College of Virginia

Richmond, Virginia, United States

Children's Hospital & Medical Center / Seattle ACTU

Seattle, Washington, United States

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, , Puerto Rico

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

San Juan City Hosp

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

Weinberg A, Huang S, Fenton T, Patterson-Bartlett J, Gona P, Read JS, Dankner WM, Nachman S; IMPAACT P1008 Team. Virologic and immunologic correlates with the magnitude of antibody responses to the hepatitis A vaccine in HIV-infected children on highly active antiretroviral treatment. J Acquir Immune Defic Syndr. 2009 Sep 1;52(1):17-24. doi: 10.1097/QAI.0b013e3181b011f6.

Reference Type: RESULT

PMID: 19617848 (View on PubMed)

Other Identifiers

PACTG P1008

Identifier Type: -

Identifier Source: secondary_id

ACTG P1008

Identifier Type: -

Identifier Source: org_study_id