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Completed

NCT Number: NCT01418014

Adolescent Master Protocol

The advances in treatment to prevent maternal HIV transmission to neonates have been groundbreaking. As a result, the number of new perinatally-infected children in the U.S. is now small. Subsequent improvements in the treatment of HIV-infected infants and children have been equally remarkable, ensuring that most previously infected American children have survived and are approaching adolescence. In addition, the number of HIV-infected adolescents worldwide is growing substantially in both resource-poor countries and in countries with increasing levels of health care. Therefore, there is a global cohort of children who have been living with HIV infection since birth who are aging into adolescence. Little is definitively known about the impact of HIV infection and its treatment on the maturation process in these children.

AMP is a prospective cohort study designed to define the impact of HIV infection and antiretroviral therapy on pre-adolescents and adolescents with perinatal HIV infection. Domains to be investigated include growth and sexual maturation, metabolic risk factors for cardiovascular disease, cardiac function, bone health, neurologic, neurodevelopment, language, hearing and behavioral function, and sexually transmitted infections (STI).

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Key information

Conditions

HIV/AIDS Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

7 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

San Juan Research Hospital, San Juan, Puerto Rico

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About this study

The primary objectives of AMP are:

  • To define the impact of HIV infection and ART on growth and pubertal development (and their hormonal regulation), along with the cognitive, academic, and social development, of pre-adolescents and adolescents with perinatal HIV infection as they move through adolescence into adulthood.
  • To identify infectious and non-infectious complications of HIV disease, including the toxicities of antiretroviral therapy (ART).
  • To investigate:
  • Cognitive and behavioral changes over time, including medication adherence, family and social function, and high risk behaviors such as risky sexual behavior, licit and illicit drug use, and alcohol use;
  • Changes in language and hearing;
  • Changes in glucose metabolism, body composition, and bone mineralization;
  • Changes in lipid metabolism and other risk factors for cardiovascular disease;
  • Risk factors for secondary transmission of HIV; and
  • The occurrence and clinical course of cervical HPV infections among females.

The domain-specific aims of AMP are:

  • Growth and sexual maturation: To longitudinally track growth and sexual maturation and the factors that influence growth and maturation in HIV-infected children when compared to HIV-exposed but uninfected children.
  • Metabolic risk factors for cardiovascular disease: To characterize the emergence of abnormal glucose metabolism, lipid abnormalities, body composition and other risk factors for cardiovascular disease and identify the contributing influences in HIV-infected children when compared to HIV-exposed but uninfected children.
  • Cardiac function: To estimate the prevalence of cardiac structural and functional abnormalities in HIV-infected children and youth when compared to HIV-exposed but uninfected children.
  • Bone mineral density: To estimate the differences in bone mineral density of HIV-infected children when compared to HIV-exposed but uninfected children and to identify factors contributing to abnormal bone mineralization.
  • Neurologic, neurodevelopment, language, and behavioral function:
  • To examine cognitive and behavioral outcomes of HIV-infected children and adolescents, including high risk behaviors such as risky sexual behavior, licit and illicit drug use, and alcohol use, neurodevelopmental impairment, school achievement and to compare them with an HIV-exposed but uninfected control cohort.
  • To examine non-adherence to antiretroviral therapy and predictors of non-adherence among HIV-infected children receiving ART.
  • To examine family and psychosocial factors associated with emotional and behavioral problems.
  • Adolescent gynecology and STI infection:
  • To evaluate the incidence of and risk factors for acquiring STIs/vaginal infections (C. trachomatis, N. gonorrhea, T. vaginalis, syphilis, genital warts, HPV, and HSV) for males and females, and in addition bacterial vaginosis for females.
  • To evaluate the incidence, predictors, and outcomes of pregnancy.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

HIV-Infected Cohort

Inclusion criteria

  • Perinatal HIV infection as documented in the medical record.
  • Age 7 years (7th birthday) up to but not including the 16th birthday at enrollment.
  • Engaged in care and ART history is available.
  • Either: Previous or current enrollment in any of the studies included on the list of approved studies allowing for enrollment into AMP as specified in the protocol. Children participating in other studies may be enrolled with approval of the Protocol Team. Additional approved protocols are listed on the PHACS website; Or: Available medical record documentation since birth of 1)ART exposure history 2)Opportunistic Infection (OI) prophylaxis exposure history 3) Viral load and CD4 count history and 4) Major medical events history
  • Willingness to participate and provide parental/legal guardian permission with assent. Children who do not know their HIV infection status will not be excluded.

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.

HIV-Uninfected, HIV-Exposed Control Cohort

Inclusion criteria

  • HIV-uninfected and born to an HIV-infected mother as documented in the medical record.
  • Age 7 years (7th birthday) up to but not including the 16th birthday at enrollment.
  • Previous or current enrollment in any of the studies included on the list of approved studies allowing for enrollment into AMP. Children participating in other studies may be enrolled with approval of the Protocol Team. Additional approved protocols will be listed on the PHACS website; Or: Available medical record documentation since birth of 1)ART exposure history and 2) Major medical events history.
  • Willingness to participate and provide parental/legal guardian permission with assent.

Exclusion criteria

None.

Treatment and study plan

Primary outcomes

  1. Abnormal growth

    Time frame: Annually for 10 years

    Assessed via measurement of height, weight, skinfold thickness, mid-upper arm and waist and hip circumference, nutrition and physical activity questionnaires ; subjects meeting growth trigger based on height measurements also have the following laboratory assessments: IGF-I, IGFBP-3, and GHBP. A growth hormone stimulation test may also be required at the recommendation of the endocrinologist.

  2. Delayed sexual maturation

    Time frame: Annually for 10 years except if subject reaches Tanner Stage 5

    Assessed via tanner staging; subjects meeting the growth trigger based on the results of the tanner staging will also have the following laboratory assessments: morning LH, FSH, estradiol, and testosterone

  3. Abnormal bone mineral density

    Time frame: Two DXAs, two years apart, per HIV-infected subject; one DXA per uninfected subject; X-ray at same time as DXA unless subject Tanner Stage 5

    Assessed via DXA scan and x-ray for bone age; subjects meeting the BMD trigger based on the DXA also have the following laboratory assessments: TSH, calcium, 25-hydroxy-vitamin D, bone-specific alkaline, N-terminal telopeptide of type I collagen phosphatase, and PTH in real time and repository specimens for assay of pro-inflammatory cytokines (IL-1, IL-6, TNF-a)

  4. Dyslipidemia

    Time frame: Annually for 10 years

    Assessed via lipid testing; subjects meeting the metabolic trigger based on the results of the lipid tests also have the following measurements: endothelial dysfunction (I, E, P-selectins: V, I-CAM-1, endothelin-1, hs-CRP, homocysteine, apolipoprotein B, lipoprotein (a), and vWF antigen)

  5. Cardiac abnormalities

    Time frame: Measured once per subject until study reached 400 echocardiograms

    Assessed through the administration of echocardiograms and serum biomarkers (ProBNP)

  6. Hearing dysfunction

    Time frame: Once per subject.

    Assessed via audiologic evaluation conducted by an audiologist.

  7. Language dysfunction

    Time frame: Annually for 10 years

    Assessed using the Woodcock and CELF IV language tests

  8. Neurodevelopmental abnormalities

    Time frame: Annually for 10 years

    Assessed via the following neurodevelopmental tests: WISC IV, WAIS IV, BRIEF, Children's Color Trails Test, Trail Making Tests, WIAT-II screen, ABAS, Parent Child Relationship Inventory, BASC-2, Quality of Life Interview, Stressful Life Events Questionnaire, Monitoring the Future

  9. Substance Use

    Time frame: Annually starting at a minimum of 10 years of age for 10 years

    The assessment of sexual activity is conducted using an Audio Computer Assisted Survey Instrument (ACASI). ACASI uses computer and voice recordings so that the participant hears (through headphones) and sees (on the screen) each question and response list. The use of ACASI is proven to minimize response bias due to the presence of an interviewer.

  10. Sexual Activity

    Time frame: Annually starting at a minimum of 10 years of age for 10 years

    The assessment of substance use is conducted using an Audio Computer Assisted Survey Instrument (ACASI). ACASI uses computer and voice recordings so that the participant hears (through headphones) and sees (on the screen) each question and response list. The use of ACASI is proven to minimize response bias due to the presence of an interviewer.

  11. Pregnancy

    Time frame: Annually for 10 years

    Assessed via medical record review to record incidents of pregnancy

  12. Sexually Transmitted Infection

    Time frame: Annually for 10 years

    Assessed via medical record review to record results of clinically conducted STI and Pap testing and pelvic exams

  13. Mitochondrial dysfunction

    Time frame: Annually for 10 years

    Assessed via measurement of serum lactate levels, OXPHO immunoassays, mitochondrial specific oxidative stress, mtDNA copies/cell, mrRNA transcripts

  14. Lactic acidosis

    Time frame: Annually for 10 years

    Assessed through the measurement of blood lactate levels using a point-of-care lactate measuring device; a single venous lactate measurement will be conducted in cases where the POC lactate measure is elevated

  15. Renal abnormalities

    Time frame: Annually for 10 years

    Assessed through the following laboratory measurements: chemistry panel, urinalysis, protein/creatinine ratio, dip stick urine test

Sponsors and collaborators

Lead sponsor

Harvard School of Public Health (HSPH)

Other

Collaborators

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

Registry information

Acronym: AMP

Important dates

Study start
2007
Primary completion
2021
Study completion
2021
First posted
Aug 16, 2011
Registry last updated
Jun 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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