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The Pediatric HIV/AIDS Cohort Study (PHACS) network was established in 2005 to address two critical pediatric HIV research questions: the long-term safety of fetal and infant exposure to prophylactic antiretroviral (ART) chemotherapy, and the effects of perinatally acquired HIV infection in adolescents. The goals of this network are to:
- Create a body of data to understand more fully the effect of HIV on sexual maturation, pubertal development, and socialization of perinatally HIV-infected pre-adolescents and adolescents;
- Acquire more definitive information regarding long-term safety of antiretroviral agents when used during pregnancy and in newborns;
- Ensure a mechanism is in place to estimate the upper bounds of risk for children associated with the use of antiretrovirals in their HIV-infected pregnant mothers as recommended in the Public Health Service Guidelines to prevent perinatal HIV transmission; and
- Ensure that the follow-up of these populations continues.
To achieve these goals, NICHD, with cofunding from NIAID, NIDA, NIDCD, NIMH,
NHLBI, OAR, NINDS, and NIAAA, awarded cooperative agreements to the Harvard School of Public Health (Harvard)
and Tulane University (Tulane). The Harvard-based PHACS Data and Operations Center,
led by Dr. George Seage, provides operations, design, methodologic, and analytic
expertise and support to the development of the PHACS research protocols. Harvard
subcontracts with Frontier Science Technology and Research Foundation in Amherst,
NY to provide data management services and with Westat in Rockville, MD to coordinate
the development of protocol documents; solicit, register, and monitor clinical sites;
plan and coordinate network meetings; and develop and maintain the PHACS website.
The PHACS Coordinating Center at Tulane, led by Dr. Russell Van Dyke, provides support and guidance to the Scientific Leadership Group (SLG), which includes experts in various scientific disciplines. The PHACS SLG is responsible for: monitoring the scientific integrity of the PHACS protocols; close examination of the data generated by those studies; and reviewing and evaluating focused substudies proposed for implementation within the PHACS network. The SLG collaborates with Harvard, NICHD, and the co funding institutes to identify the critical research questions and the best scientific methodology with which to address them. In 2008, the PHACS SLG formed scientific working groups (WG). The WGs are responsible for close examination of the data in their domain and for the development of abstracts for presentation and manuscript publication. Little more than a year after these WGs were formed, multiple abstracts have been accepted for presentation at four national and international scientific conferences. Please visit the "Publications and Presentations" section in the "Library" to view these abstracts.
PHACS STUDIES – SMARTT
Surveillance Monitoring for ART Toxicities Study in HIV-uninfected Children Born
to HIV-infected Women (SMARTT) follows two cohorts of
HIV- and ART-exposed but uninfected children: the Static and
Dynamic Surveillance cohorts. Enrollment into the Static cohort, which includes children less than 12 years of age, closed with a final cohort of 1,240 subjects. Enrollment into the
Dynamic cohort will remain open for an indefinite period, with the goal of enrolling up to 400 HIV-exposed but uninfected newborns per year. Please see the “Quarterly Administrative Report”, located in the “Study Documents” section, for the most up-to-date dynamic cohort enrollment numbers. PHACS will study both cohorts to estimate
the incidence of conditions and diagnoses potentially related to
in utero exposure to antiretroviral therapy and/or
exposure in the first two months of life among children born to
HIV-infected mothers (source population). Occurrences of
abnormalities from ART exposure in utero
and/or in the first two months of life will be sought in multiple domains, including
metabolic and growth, cardiac, neurological, neurodevelopmental, behavior, language,
and hearing domains. The SMARTT domain-specific objectives are to:
- Metabolic Function and Growth
Estimate the occurrence of abnormal signals of somatic growth and body composition.
Estimate the occurrence of abnormal signals in measures of organ function, including
the liver, muscles, and pancreas.
Evaluate other toxin exposures (e.g., licit and illicit drug exposure
in utero or other toxins such as lead after birth) that may be alternative
explanations for abnormal signals.
- Cardiac Function
abnormalities in cardiac function related to ART and/or HIV
exposure and to examine the utility of serum biomarkers as
surrogate markers of cardiac dysfunction
- Neurologic, Neurodevelopmental, Behavior, Language, and
Identify age-specific signals of neurological, neurodevelopmental, linguistic, social,
and behavioral dysfunction.
Identify other neurologic conditions such as microcephaly, stroke, and febrile and
Identify adverse signals of hearing dysfunction.
- Other Domains of Interest
Identify diagnoses and conditions of interest including but not limited to birth
defects, unexplained death, and abnormalities of the hematopoeitic system.
PHACS STUDIES – AMP
Adolescent Master Protocol (AMP) includes children ages 7 years until their 16th birthday born to HIV-infected mothers. Enrollment is now closed with the perinatally exposed HIV-infected cohort enrolling a total of 451 children and the comparison group, consisting of perinatally exposed HIV-uninfected children, enrolling a final cohort of 227 children.
This study is 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 adolescent gynecology and HPV infection. The AMP domain-specific objectives are to:
- Growth and sexual maturation
Longitudinally track growth and sexual maturation and the factors that influence
growth and maturation.
- Metabolic risk factors for cardiovascular disease
Characterize the emergence of abnormal glucose metabolism, lipid abnormalities,
body composition and other risk factors for cardiovascular disease and identify
the contributing influences.
- Cardiac function
Estimate the prevalence of cardiac structural and functional abnormalities in HIV-infected
children and youth.
- Bone mineral density
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
- Neurologic, neurodevelopment, language, and behavioral
Examine cognitive and behavioral outcomes of HIV-infected subjects, 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.
Examine non-adherence to antiretroviral therapy and predictors of non-adherence
among HIV-infected children receiving ART.
Examine family and psychosocial factors associated with emotional and behavioral
- Adolescent gynecology and HPV infection
Evaluate the occurrence and clinical course of cervical HPV infections and cervical
abnormalities in perinatally HIV-infected and HIV-exposed but uninfected sexually
active females who are having gynecologic exams performed as standard of care.
Co-enrollment of SMARTT children in the AMP protocol as uninfected control subjects, or AMP uninfected subjects in the SMARTT Static Cohort is allowed. When such co-enrollment occurs, the patient ID number (PID) will remain the same for both protocols. Sites are requested to notify both protocol teams when a child is co-enrolled in AMP and SMARTT.
Enrollment of PHACS subjects into other non-PHACS protocols will occur at the discretion of the local Principal Investigator. However, she/he must take into account any issues that enrollment in the additional study may require, which may compromise the site’s ability to fulfill the requirements of PHACS.
PHACS will enroll subjects who may have been previously enrolled in another study with shared goals and similar data collection as PHACS. For these subjects, the burden of data collection will be reduced for clinical sites as PHACS has negotiated formal agreements with many studies to share data. The list of the approved studies can be located in the current study protocol in the Study Documents folder of the Documents section. The parent or legal guardian will be asked to grant permission for the other study to release data to PHACS.
The PHACS Data and Operations Center solicited applications from clinical sites to participate in the PHACS studies. After review, 24 clinical sites across 13 states and Puerto Rico were selected. Of those, 22 participate in SMARTT and 15 participate in AMP, with the majority conducting both protocols. A list of these sites can be found in the "Directory Search" of the "Contact List".
Both protocols are structured to accommodate focused sub-studies as identified by the SLG, the NIH program scientists, the PHACS clinical sites, the HIV clinical research networks supported by NICHD and the collaborators listed above, or by independent investigators conducting HIV-related research funded by NIH Institutes and Centers.
CONCEPT SHEET TEMPLATE
The PHACS Development of a Protocol or Data Analysis Concept Capsule Submission Template can be found on the PHACS website in the Analyses folder, in the Templates and Guidelines folder.