Adolescent Master Protocol

The primary objectives of AMP are:

1. 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.

2. To identify infectious and non-infectious complications of HIV disease, including the
toxicities of antiretroviral therapy (ART).

3. 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:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

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. 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 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.