Clinical trial NCT00001078: A Study on the Rate of Opportunistic (AIDS-Related) Infections Among HIV-Positive Children Who Have Stopped Taking Their OI Preventive Medications
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Viral Vaccines
AIDS-Related Opportunistic Infections
Anti-HIV Agents
Hepatitis A Virus, Human
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 200
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

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