Adolescent Master Protocol for Participants 18 Years of Age and Older (AMP Up) (AMP Up)

• ClinicalTrials.gov Identifier: NCT02119702
• Recruitment Status: Recruiting
• First Posted: April 22, 2014
• Last Update Posted: October 26, 2020
• Sponsor: Harvard School of Public Health
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute on Drug Abuse (NIDA); National Institute of Allergy and Infectious Diseases (NIAID); NIH Office of AIDS Research (OAR); National Institute of Mental Health (NIMH); National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Deafness and Other Communication Disorders (NIDCD); National Heart, Lung, and Blood Institute (NHLBI); National Institute of Dental and Craniofacial Research (NIDCR); National Institute on Alcohol Abuse and Alcoholism (NIAAA); Tulane University School of Medicine
• Information provided by (Responsible Party): George Seage, Harvard School of Public Health

Tracking Information

• First Submitted Date: April 10, 2014
• First Posted Date: April 22, 2014
• Last Update Posted Date: October 26, 2020
• Study Start Date: April 2014
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2014)

• HIV disease progression [ Time Frame: Annually for 6 years ]
  Factors of interest for this outcome include virologic suppression, immune impairment, immune activation, changes in ART, cumulative exposure to specific ART, viral resistance, co-infections, and host genetic polymorphisms. Data will be collected through chart abstraction and laboratory assessments.
• Metabolic abnormalities [ Time Frame: Annually for 6 years ]
  Factors of interest include BMI, body composition, systolic and diastolic blood pressure, lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides). Data will be collected by chart review, physical assessments, and laboratory evaluations.
• Sexually transmitted infections [ Time Frame: Annually for 6 years ]
  STI testing and chart review conducted annually.
• Pregnancies [ Time Frame: Annually for 6 years ]
  Data collected annually through online surveys and chart abstraction.
• Mental health problems [ Time Frame: Every 3 years for 6 years ]
  Assessed at Entry, Year 3, and Year 6 visits through the NIH Toolbox and Center for Epidemiologic Studies Depression Scale (CES-D).
• ART adherence [ Time Frame: Annually for 6 years ]
  Data collected annually through an online survey.
• Prevalence of risk behaviors including risky sexual behavior and licit and illicit substance use [ Time Frame: Annually for 6 years ]
  Participants will complete an annual online survey.
• Transition to adult functioning [ Time Frame: Annually for 6 years ]
  Every year participants will complete an online survey to collect data on educational attainment, employment, independent living and quality of life.
• Hearing dysfunction [ Time Frame: Every 3 years for 6 years ]
  Assessed through the NIH Toolbox and a questionnaire to be completed at Entry, Year 3 and Year 6 visits.
• Language development [ Time Frame: Once, at the Entry or Year 3 visit ]
  The Clinical Evaluation of Language Fundamentals (CELF) IV assessment will be completed at the Entry or Year 3 visit.
• End-organ disease [ Time Frame: Annually for 6 years ]
  Factors of interest for this outcome include virologic suppression, immune impairment, immune activation, changes in ART, cumulative exposure to specific ART, viral resistance, co-infections, and host genetic polymorphisms. Data will be collected through chart abstraction and laboratory assessments.
• Mortality [ Time Frame: Annually for 6 years ]
  Factors of interest for this outcome include virologic suppression, immune impairment, immune activation, changes in ART, cumulative exposure to specific ART, viral resistance, co-infections, and host genetic polymorphisms. Data will be collected through chart abstraction and laboratory assessments.
• Risk factors for cardiovascular disease [ Time Frame: Annually for 6 years ]
  Factors of interest include BMI, body composition, systolic and diastolic blood pressure, lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) and cumulative cardiometabolic risk. Data will be collected by chart review, physical assessments, and laboratory evaluations.
• Cervical HPV-associated pre-cancers and cancers (among female participants) [ Time Frame: Annually for 6 years ]
  Data collected through annual chart review.
• Cognitive impairment [ Time Frame: Every 3 years for 6 years ]
  Assessed at Entry, Year 3, and Year 6 visits through the NIH Toolbox.
• Maternal-to-child HIV transmission [ Time Frame: Annually for 6 years ]
  Data collected through annual chart review.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Adolescent Master Protocol for Participants 18 Years of Age and Older (AMP Up)
• Official Title: Adolescent Master Protocol for Participants 18 Years of Age and Older (AMP Up)
• Brief Summary: This is a prospective cohort study designed to define the impact of HIV infection and antiretroviral therapy (ART) on young adults with perinatal HIV infection as they transition into adulthood. A group of perinatally HIV-exposed, -uninfected (PHEU) young adults from a similar sociodemographic background and age distribution will be enrolled for comparison.

Detailed Description

AMP Up aims to define the impact of HIV infection and antiretroviral therapy (ART) on young adults with perinatal HIV infection as they transition into adulthood. A group of perinatally HIV-exposed, -uninfected (PHEU) young adults from a similar sociodemographic background and age distribution will be enrolled for comparison.

The primary objectives of this study are:

• To identify infectious and non-infectious complications of HIV disease and toxicities resulting from long-term ART, including disease progression, immune dysfunction, viral resistance, end-organ disease, and mortality.

• To define the impact of HIV infection and ART on the long-term clinical outcomes of young adults, including:

  • Metabolic abnormalities and risk factors for cardiovascular disease, including glucose and lipid metabolism, blood pressure, and body composition.
  • Sexually transmitted infections (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, syphilis, human papillomavirus, genital warts and HSV) among males and females, and cervical HPV-associated pre-cancers and cancers and Mycoplasma genitalium and other vaginal microbiota among females.
  • Reproductive health, fertility, and pregnancy outcomes including mother-to-child transmission of HIV.

• To define the impact of perinatal HIV infection and ART on long-term neurocognitive and behavioral health outcomes, including:

  • Mental health and neurocognitive functioning.
  • Health care behaviors, including adherence to ART, participation in health care services, and transition to adult clinical care.
  • Risk behaviors, including sexual behavior and substance use.
  • Independent living skills, and vocational and education achievement necessary for successful transition to adult functioning and quality of life.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Plasma, serum, peripheral blood monocuclear cells (PBMCs), urine, throat wash/gargle, saliva, and vaginal swabs.

• Sampling Method: Non-Probability Sample
• Study Population: HIV-infected and -uninfected young adults 18 years of age or older at the time of enrollment born to HIV-infected mothers.
• Condition: HIV/AIDS
• Intervention: Not Provided

Study Groups/Cohorts

• Infected Cohort
  Perinatally HIV-infected participants at or beyond their 18th birthday at enrollment, engaged in care with ART treatment history available.
• Uninfected Cohort
  Perinatally HIV-exposed, perinatally-uninfected participant at or beyond their 18th birthday at enrollment. Must have been previously or currently enrolled in PHACS AMP or PHACS SMARTT, and may have horizontally-acquired HIV infection.

Publications *

• Tassiopoulos K, Patel K, Alperen J, Kacanek D, Ellis A, Berman C, Allison SM, Hazra R, Barr E, Cantos K, Siminski S, Massagli M, Bauermeister J, Siddiqui DQ, Puga A, Van Dyke R, Seage GR 3rd; Pediatric HIV/AIDS Cohort Study. Following young people with perinatal HIV infection from adolescence into adulthood: the protocol for PHACS AMP Up, a prospective cohort study. BMJ Open. 2016 Jun 9;6(6):e011396. doi: 10.1136/bmjopen-2016-011396.
• Williams PL, Jesson J. Growth and pubertal development in HIV-infected adolescents. Curr Opin HIV AIDS. 2018 May;13(3):179-186. doi: 10.1097/COH.0000000000000450. Review.
• Innes S, Patel K. Noncommunicable diseases in adolescents with perinatally acquired HIV-1 infection in high-income and low-income settings. Curr Opin HIV AIDS. 2018 May;13(3):187-195. doi: 10.1097/COH.0000000000000458. Review.
• Goodenough CJ, Patel K, Van Dyke RB; Pediatric HIV/AIDS Cohort Study (PHACS). Is There a Higher Risk of Mother-to-child Transmission of HIV Among Pregnant Women With Perinatal HIV Infection? Pediatr Infect Dis J. 2018 Dec;37(12):1267-1270. doi: 10.1097/INF.0000000000002084.
• Wilkinson JD, Williams PL, Yu W, Colan SD, Mendez A, Zachariah JPV, Van Dyke RB, Shearer WT, Margossian RE, Lipshultz SE; Pediatric HIV/AIDS Cohort Study (PHACS). Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed uninfected children. AIDS. 2018 Jun 19;32(10):1267-1277. doi: 10.1097/QAD.0000000000001810.
• Alperen J, Davidson J, Siminski S, Seage GR 3rd; Pediatric HIV/AIDS Cohort Study. Utility of the National Death Index in Identifying Deaths in a Clinic-Based, Multisite Cohort: The Experience of the Pediatric HIV/AIDS Cohort Study. J Acquir Immune Defic Syndr. 2018 Sep 1;79(1):e37-e39. doi: 10.1097/QAI.0000000000001763.
• Kacanek D, Huo Y, Malee K, Mellins CA, Smith R, Garvie PA, Tassiopoulos K, Lee S, Berman CA, Paul M, Puga A, Allison S; Pediatric HIV/AIDS Cohort Study. Nonadherence and unsuppressed viral load across adolescence among US youth with perinatally acquired HIV. AIDS. 2019 Oct 1;33(12):1923-1934. doi: 10.1097/QAD.0000000000002301.
• Moscicki AB, Karalius B, Tassiopoulos K, Yao TJ, Jacobson DL, Patel K, Purswani M, Seage GR; Pediatric HIV/AIDS Cohort Study. Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus-infected and Exposed, Uninfected Youth. Clin Infect Dis. 2019 Sep 13;69(7):1183-1191. doi: 10.1093/cid/ciy1040.
• Yildirim C, Garvie PA, Chernoff M, Wilkins ML, Patton ED, Williams PL, Nichols SL; Memory and Executive Functioning Study of the Pediatric HIV/AIDS Cohort Study. The Role of Pharmacy Refill Measures in Assessing Adherence and Predicting HIV Disease Markers in Youth with Perinatally-Acquired HIV (PHIV). AIDS Behav. 2019 Aug;23(8):2109-2120. doi: 10.1007/s10461-019-02468-x.
• Patel K, Seage GR 3rd, Burchett SK, Hazra R, Van Dyke RB; Pediatric HIV/AIDS Cohort Study. Disparities in HIV Viral Suppression Among Adolescents and Young Adults by Perinatal Infection. Am J Public Health. 2019 Jul;109(7):e9. doi: 10.2105/AJPH.2019.305108.
• Smith R, Huo Y, Tassiopoulos K, Rutstein R, Kapetanovic S, Mellins C, Kacanek D, Malee K; Pediatric HIV/AIDS Cohort Study (PHACS). Mental Health Diagnoses, Symptoms, and Service Utilization in US Youth with Perinatal HIV Infection or HIV Exposure. AIDS Patient Care STDS. 2019 Jan;33(1):1-13. doi: 10.1089/apc.2018.0096.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 17, 2014): 850
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2021
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Perinatally HIV-Infected Cohort

Inclusion Criteria:

• Perinatal HIV infection as documented in the medical record
• At or beyond their 18th birthday at the time of informed consent with no upper age limit
• Engaged in medical care and medical records are available

• At least one of the following is true:

  • Previously or currently enrolled in PHACS AMP, or
  • Previously enrolled in any of the studies included on the list of approved studies for enrollment into AMP Up, or

  • Available medical record documentation since early childhood of:

    • ART exposure history
    • Opportunistic infection prophylaxis exposure history
    • Viral load and CD4+ cell count history
    • Major medical events history
• Willingness to participate and provide legal written consent

Exclusion Criteria:

• HIV acquired by other than maternal-child transmission (e.g., blood products, sexual contact, and IV drug use) as documented in the medical record

Perinatally HIV-Exposed, -Uninfected Cohort

Inclusion Criteria:

• Perinatally HIV-exposed, perinatally-uninfected as indicated in the medical record; the PHEU participant may have horizontally-acquired HIV infection
• At or beyond their 18th birthday at the time of informed consent with no upper age limit

• At least one of the following is true:

  • Previously or currently enrolled in PHACS AMP, or
  • Previously or currently enrolled in PHACS SMARTT
• Willingness to participate and provide legal written consent

Exclusion Criteria:

• Have confirmed perinatal HIV infection as documented in the medical record

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Liz Salomon, EdM; 617-432-6762; lsalomon@hsph.harvard.edu

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT02119702
• Other Study ID Numbers: HD052102 - PH300; PH300 ( Other Identifier: PHACS Protocol Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: George Seage, Harvard School of Public Health
• Study Sponsor: Harvard School of Public Health

Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• National Institute on Drug Abuse (NIDA)
• National Institute of Allergy and Infectious Diseases (NIAID)
• NIH Office of AIDS Research (OAR)
• National Institute of Mental Health (NIMH)
• National Institute of Neurological Disorders and Stroke (NINDS)
• National Institute on Deafness and Other Communication Disorders (NIDCD)
• National Heart, Lung, and Blood Institute (NHLBI)
• National Institute of Dental and Craniofacial Research (NIDCR)
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Tulane University School of Medicine

Investigators

• Principal Investigator: George R Seage III, ScD, MPH; Harvard School of Public Health
• Principal Investigator: Russell Van Dyke, MD; Tulane University School of Medicine

• PRS Account: Harvard School of Public Health
• Verification Date: October 2020