Clinical trial NCT00001097: Long-Term Effects of HAART in Youth With Stronger Immune Systems Versus Youth With Weaker Immune Systems
Official title: Establishment and Maintenance of Long-Term Undetectable Plasma HIV-1 RNA: Correlation With Immunologic Reconstitution and Viral Dynamics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-HIV Agents
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: 120
Sex: ALL
Minimum age (years): 8
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no

Brief summary: The purpose of this study is to see if children and young adults with better immune systems before starting highly active antiretroviral therapy (HAART) do better than those who have weaker immune systems before starting HAART.

HIV infection weakens the immune system's ability to fight other infections and diseases. HAART is a type of anti-HIV therapy shown to improve the immune system of adults. However, not all patients show the same amount of improvement with HAART. Doctors believe that results may depend on how strong a patient's immune system is before starting HAART. Long-term effects of HAART in children and young adults have not yet been studied.

Detailed description: Recent adult clinical trials involving combination HAART, including a protease inhibitor (PI), have demonstrated improvements in somatic immune system functioning. \[AS PER AMENDMENT 2/27/01: More recently, similar success has been demonstrated with a PI-sparing regimen, zidovudine, lamivudine, and efavirenz.\] Not all individuals, however, experience the same level of immune reconstitution, and oftentimes any improvement is short-lived. Adolescent patients may have a greater potential for immune restoration because of residual thymic tissue and therefore may experience greater long-term virus-free states as compared to adult patients. This study examines the duration of virologic efficacy HAART has on the adolescent HIV-positive population.

Patients begin study by initiating a HAART regimen of a minimum of 3 drugs, at least 1 of which must be a PI \[AS PER AMENDMENT 2/27/01: or efavirenz (EFV)\]. A variety of drug combinations are used; therefore, patients are grouped according to the classes of drugs in their respective regimen (e.g., 2 nucleoside reverse transcriptase inhibitors \[NRTIs\] plus 1 PI; 2 NRTIs plus 2 PIs; 1 or 2 NRTIs plus 1 PI plus 1 nonnucleoside reverse transcriptase inhibitor \[NNRTI\] \[AS PER AMENDMENT 2/27/01: ; and 2 NRTIs plus EFV\]). At the time of HAART initiation, patients undergo immunologic and virologic assessments in order to determine baseline values. Then, to determine the virologic success or failure of HAART, HIV-1 RNA measurements are taken and compared to initial baseline values. Virologic success equals undetectable HIV-1 RNA at Week 12 \[AS PER AMENDMENT 2/27/01: and confirmed at Week 16\] or a significant (greater than 1 log) decrease in HIV-1 RNA from baseline to Week 12 \[AS PER AMENDMENT 2/27/01: and confirmed undetectable HIV-1 RNA before the next scheduled visit (Week 24)\]. Patients are followed for a minimum of 3 years of maintained viral suppression or until they have demonstrated virologic failure. From these values, any correlation that may exist between HIV-1 RNA values and HAART can be deduced. Patients with virologic failure on the initial HAART regimen may be allowed to change to a second HAART regimen. \[AS PER AMENDMENT 2/27/01: Patients with virologic success on the second HAART regimen are followed for a minimum of 3 years.\] Patients with virologic failure on the second HAART regimen or who voluntarily discontinue HAART are followed using an abbreviated schedule for 3 years.

Eligibility criteria: Inclusion Criteria

Children may be eligible for this study if they:

* Are HIV-positive.
* Are between 8 and 22 years old (consent of parent or guardian required if under 18).
* Have detectable levels of HIV in the blood within 30 days prior to study entry.
* Expect to be on the study for at least 1 year. (This study has been changed by adding this requirement.)
* Are pregnant and are not taking didanosine/stavudine (ddI/d4T) or EFV as part of their HAART regimen. (This study has been changed so that pregnant patients may be eligible if they are not taking ddI/d4T or EFV.)

Exclusion Criteria

Children will not be eligible for this study if they:

* Are taking HAART or more than 1 anti-HIV drug.
* Were infected with HIV before birth, at the time of delivery, or by a blood transfusion during birth.
* Have taken part in the study before.
* Have not responded well to HAART in the past.
* Have taken drugs to boost the immune system such as HIV vaccines, IVIG, or cytokine therapy.
* Have AIDS-related (opportunistic) infection at the time of screening. (This study has been changed so that patients with an AIDS-related infection are ineligible.)
* Are pregnant and are taking ddI/d4T or EFV as part of their HAART regimen. (This study has been changed so that pregnant patients are ineligible if they are taking ddI/d4T or EFV.)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham - Pediatric
state: Alabama
city: Mobile
country: United States
facility: Univ of South Alabama
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: 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: Denver
country: United States
facility: Children's Hosp of Denver
state: Colorado
city: Farmington
country: United States
facility: Connecticut Children's Med Ctr
state: Connecticut
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: North Broward Hosp District
state: Florida
city: Gainesville
country: United States
facility: Univ of Florida Gainesville
state: Florida
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: Chicago
country: United States
facility: Univ of Chicago Children's Hosp
state: Illinois
city: New Orleans
country: United States
facility: Earl K Long Early Intervention Clinic
state: Louisiana
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: 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: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Bronx
country: United States
facility: Montefiore Med Ctr Adolescent AIDS Program
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: Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Harlem Hosp Ctr
state: New York
city: Syracuse
country: United States
facility: SUNY Health Sciences Ctr at Syracuse / Pediatrics
state: New York
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hosp of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Saint Jude Children's Research Hosp of Memphis
state: Tennessee
city: Dallas
country: United States
facility: Children's Med Ctr of Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
city: Norfolk
country: United States
facility: Children's Hosp of the King's Daughters
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: Patricia Flynn
role: STUDY_CHAIR
References:
citation: Flynn P, Douglas S, Rudy B, Lathey J, Lindsey J, Wang Y. Establishment and maintenance of long-term undetectable plasma HIV-1 RNA: correlation with immunologic reconstitution and viral dynamics. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 692)
citation: Wu H, Lathey J, Ruan P, Douglas SD, Spector SA, Lindsey J, Hughes MD, Rudy BJ, Flynn PM; PACTG 381 Team. Relationship of plasma HIV-1 RNA dynamics to baseline factors and virological responses to highly active antiretroviral therapy in adolescents (aged 12-22 years) infected through high-risk behavior. J Infect Dis. 2004 Feb 15;189(4):593-601. doi: 10.1086/381500. Epub 2004 Jan 29.
citation: Flynn PM, Rudy BJ, Douglas SD, Lathey J, Spector SA, Martinez J, Silio M, Belzer M, Friedman L, D'Angelo L, McNamara J, Hodge J, Hughes MD, Lindsey JC; Pediatric AIDS Clinical Trial Group 381 Study Team. Virologic and immunologic outcomes after 24 weeks in HIV type 1-infected adolescents receiving highly active antiretroviral therapy. J Infect Dis. 2004 Jul 15;190(2):271-9. doi: 10.1086/421521. Epub 2004 Jun 18.
citation: Rudy BJ, Lindsey JC, Flynn PM, Bosch RJ, Wilson CM, Hughes ME, Douglas SD; Pediatric Aids Clinical Trials Group 381 Study Team. Immune reconstitution and predictors of virologic failure in adolescents infected through risk behaviors and initiating HAART: week 60 results from the PACTG 381 cohort. AIDS Res Hum Retroviruses. 2006 Mar;22(3):213-21. doi: 10.1089/aid.2006.22.213.
citation: Flynn PM, Rudy BJ, Lindsey JC, Douglas SD, Lathey J, Spector SA, Martinez J, Silio M, Belzer M, Friedman L, D'Angelo L, Smith E, Hodge J, Hughes MD; PACTG 381 Study Team. Long-term observation of adolescents initiating HAART therapy: three-year follow-up. AIDS Res Hum Retroviruses. 2007 Oct;23(10):1208-14. doi: 10.1089/aid.2006.0290.