Clinical trial NCT00683579: Neurocognitive Assessment in Youth Initiating HAART
Official title: Neurocognitive Assessment in Youth Initiating HAART
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HAART
DHHS guidelines
Treatment Naive
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
First posted: 2008-05-23
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 24
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: English or Spanish speaking youth, 18 years 0 days to 24 years 364 days, with HIV-1 infection acquired after age 9 via behavioral means, in the following immunological and treatment categories:

1. Early initiation of HAART and enrolled in 061 Arm A; CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml;
2. Initiation of HAART per DHHS guidelines (standard of care) but not yet meeting criteria. There will be 25 participants from ATN 061 preferentially enrolled into this protocol; an additional 25 participants will be enrolled with similar biomedical characteristics.
3. Initiation of HAART per DHHS guidelines (not part of ATN 061).
4. Meeting DHHS guidelines for initiating HAART, but not initiating due to unwillingness or providers' expectation of poor adherence.

Brief summary: ATN 071 is a prospective cohort study comparing neurocognitive functioning in four groups of youth, age 18-24: Two groups with CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml, one initiating HAART (Group 1) and the other not initiating treatment (Group 2); and two groups with CD4+ T cells \< 350 cells/mm3, one initiating treatment (Group 3) and the other not initiating treatment (Group 4). Groups 2 and 3 represent standard of care. Group 1 and a portion of group 2 will be co-enrolled in ATN 061 and will be randomly assigned to group by that protocol.


Eligibility criteria: Inclusion Criteria:

Groups 1 and 2 (If co-enrolling in ATN 061)

* HIV positive participants age 18 years and 0 days to 24 years and 364 days (the lower age limit of this study is driven by the restriction of ATZ use to age 18 and greater);
* Groups 1 and 2: CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml, as determined by two consecutive measures within 6 months of entry with the second measure being collected at pre-entry to ATN 061;
* Infected with HIV after the age of nine via behavioral means;
* Naïve to ART except for HAART for PMTCT for six months or less with at least six months since the time of exposure;
* HIV genotype without major resistance mutations to the recommended ATV-r based HAART regimens;
* Able to provide written informed consent as determined by local Institutional Review Boards;
* Fluent in English or Spanish.

Group 2, enrolled in ATN 071 and not ATN 061

* CD4+ T cells above 350 cells/mm3 and HIV RNA \>1,000 copies/ml, as determined by most recent laboratory evaluations available within 4 months prior to entry;
* Not prescribed HAART according to DHHS guidelines.

Groups 3 and 4:

* HIV positive participants age 18 years and 0 days to 24 years and 364 days;
* Infected with HIV after the of age nine via behavioral means;
* Naïve to ART except for HAART for PMTCT for six months or less with at least six months since the time of exposure;
* Able to provide written informed consent as determined by local Institutional Review Boards;
* Fluent in English or Spanish.
* CD4+ T cells \< 350 cells/mm3, as determined by most recent laboratory evaluations available within 4 months prior to entry.

Group 3 ONLY:

* Participant initiating HAART.

Group 4 ONLY:

* HAART has not been prescribed due to either participant's refusal to initiate HAART or provider's concerns about participant's predicted inability to adhere to regimen.

Exclusion Criteria:

Groups 1 and 2:

* For Groups 1 and 2: any history of an AIDS-defining illness;
* Active drug or alcohol use or dependence that, in the opinion of the site personnel, would interfere with meeting study requirements;
* History of cognitive or motor impairment due to non-HIV-related conditions (for example, prematurity, cerebral palsy, closed head injury, CNS cancer or cranial irradiation, etc.) or psychosis. Youth with diagnoses of learning disabilities or attention deficit hyperactivity disorder will be allowed in the study;
* Enrollment of youth with chronic or acute medical conditions other than HIV that could potentially impact upon neurocognitive functioning requires protocol chair approval.
* Pregnancy at any time during the study including entry.

Primary outcomes:
measure: The impact of early initiation of HAART on preventing neurocognitive decline in HIV infected adolescents compared to no treatment and initiation following current guidelines.
timeFrame: 3 years
Secondary outcomes:
measure: Assess youth who meet current DHHS guidelines for initiating HAART but either refuse to start HAART or are not prescribed HAART because of concerns about adherence.
timeFrame: Baseline assessment (not longitudinal)
measure: To assess if de-intensification of HAART as will occur in Arm A of ATN 061 can minimally maintain neurocognitive gains made with one year of HAART.
timeFrame: 3 years
measure: To assess the relationship of neurocognitive functioning to CD4+ and viral load at baseline in adolescents with HIV-1 infection (groups 1 and 2 versus 3 and 4).
timeFrame: 3 years
measure: To correlate neurocognitive change with changes in CD4+ and viral loads within groups.
timeFrame: 3 years
measure: To assess the incidence of HIV-associated dementia and minor cognitive-motor disorder in adolescents with risk-acquired HIV infection.
timeFrame: 3 years
measure: To evaluate the relationship of current substance abuse to neurocognitive deficits in youth with risk-acquired HIV.
timeFrame: 3 years
measure: To assess the relationship of neurocognitive functioning to available biomarkers within the subset of participants co-enrolled in ATN 061 (for example, immune activation markers, viral phenotype, CD4 and CD8 subsets).
timeFrame: 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hopsital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of Southern California - IMPAACT Site
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital of Denver - IMPAACT Site
state: Colorado
city: Washington
country: United States
facility: Childrens National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Howard University - IMPAACT Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic and Treatment Center
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Stroger Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Childrens Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University - IMPAACT Site
state: Maryland
city: Detroit
country: United States
facility: Children's Hospital of Michigan - IMPAACT Site
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhattan
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Center
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital - IMPAACT Site
state: Tennessee
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: Adolescent Trials Network
name: Sharon Nichols
role: STUDY_CHAIR
References:
citation: Kohn JN, Loop MS, Kim-Chang JJ, Garvie PA, Sleasman JW, Fischer B, Rendina HJ, Woods SP, Nichols SL, Hong S. Trajectories of Depressive Symptoms, Neurocognitive Function, and Viral Suppression With Antiretroviral Therapy Among Youth With HIV Over 36 months. J Acquir Immune Defic Syndr. 2021 Jun 1;87(2):851-859. doi: 10.1097/QAI.0000000000002653.