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

HIV Infections Clinical Trial

Official title:

An Observational Study of the Rate of Opportunistic Infection Events in HIV-Infected Children Who Have Demonstrated Immunologic Reconstitution and Who Have Discontinued OI Prophylaxis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001078
• Other study ID #: ACTG P1008
• Secondary ID: PACTG P1008
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: March 1, 2011

Study information

• Verified date: July 2005
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. primary completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 21 Years

Eligibility

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.

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infection
• Opportunistic Infections

Intervention

Biological:
• Hepatitis A Vaccine (Inactivated)

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
United States	Emory Univ Hosp / Pediatrics	Atlanta	Georgia
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Univ of Alabama at Birmingham - Pediatric	Birmingham	Alabama
United States	Boston City Hosp / Pediatrics	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	SUNY - Brooklyn	Brooklyn	New York
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	Columbus Children's Hosp	Columbus	Ohio
United States	Children's Hosp of Denver	Denver	Colorado
United States	Children's Hosp of Michigan	Detroit	Michigan
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	North Shore Univ Hosp	Great Neck	New York
United States	Univ of Mississippi Med Ctr	Jackson	Mississippi
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
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	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	UMDNJ - Robert Wood Johnson Med School / Pediatrics	New Brunswick	New Jersey
United States	Yale Univ Med School	New Haven	Connecticut
United States	Schneider Children's Hosp	New Hyde Park	New York
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med 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	Metropolitan Hosp Ctr	New York	New York
United States	Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	Children's Hosp of Oakland	Oakland	California
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hosp	Phoenix	Arizona
United States	Med College of Virginia	Richmond	Virginia
United States	Palm Beach County Health Dept	Riviera Beach	Florida
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Children's Hospital & Medical Center / Seattle ACTU	Seattle	Washington
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	State Univ of New York at Stony Brook	Stony Brook	New York
United States	Children's Hosp of Washington DC	Washington	District of Columbia
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Univ of Massachusetts Med School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

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 ac — View Citation

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