Neurocognitive Assessment in Youth Initiating HAART

Study Overview
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Brief Summary
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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.

Official Title
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Neurocognitive Assessment in Youth Initiating HAART

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Early Treatment with HAART
* Other: No treatment
* Drug: HAART Treatment - standard care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Participants with CD4+ T cells above 350 cells/mm3 and HIV RNA >1,000 copies/ml who are initiating HAART with possibility of de-intensification (early treatment). | Drug: Early Treatment with HAART<br>* HAART with possibility of de-intensification<br>|
| 2<br>Participants with CD4+ T cells above 350 cells/mm3 and HIV RNA >1,000 copies/ml who are not initiating treatment. | Other: No treatment<br>* No treatment. For group 2, participants do not yet meet DHHS guidelines. For group 4, treatment is not initiated due to unwillingness or providers' expectation of poor adherence.<br>|
| 3<br>Participants with CD4+ T cells < 350 cells/mm3 who are initiating treatment. | Drug: HAART Treatment - standard care<br>* Initiation of HAART per DHHS guidelines, i.e. starting treatment and CD4+ T cells less than 350 cells/mm3 or HIV RNA >100,000 copies/ml<br>|
| 4<br>Participants with CD4+ T cells < 350 cells/mm3 who are not initiating treatment. | Other: No treatment<br>* No treatment. For group 2, participants do not yet meet DHHS guidelines. For group 4, treatment is not initiated due to unwillingness or providers' expectation of poor adherence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The impact of early initiation of HAART on preventing neurocognitive decline in HIV infected adolescents compared to no treatment and initiation following current guidelines. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | Baseline assessment (not longitudinal) | 
| 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. |  | 3 years | 
| 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). |  | 3 years | 
| To correlate neurocognitive change with changes in CD4+ and viral loads within groups. |  | 3 years | 
| To assess the incidence of HIV-associated dementia and minor cognitive-motor disorder in adolescents with risk-acquired HIV infection. |  | 3 years | 
| To evaluate the relationship of current substance abuse to neurocognitive deficits in youth with risk-acquired HIV. |  | 3 years | 
| 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). |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAART, DHHS guidelines, Treatment Naive