Antiretroviral ToxicitySMARTTNCT01310023
Surveillance Monitoring for ART Toxicities Study in HIV Uninfected Children Born to HIV Infected Women
An observational study of Antiretroviral Toxicity, run by Harvard School of Public Health (HSPH) at 22 sites in 2 countries.
Trial summary
SMARTT will 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 of HIV-infected mothers. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Antiretroviral Toxicity
- How many people
- 5,169 participants
- Where
- 22 sitesin 2 countries
- Study dates
- Mar 2007to 31 May 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Children aged 0 - < 12 years born of HIV-infected mothers recruited from a clinical setting.
Who may be able to join
- Dynamic Cohort:
- HIV-exposed living fetus greater than or equal to 23 weeks gestation or a live infant born after 22 weeks gestation. Infants exposed and unexposed to ART will be enrolled.
- Any infant born of an HIV-infected mother may be enrolled pending determination of the infant's HIV infection status. However, infants found to be HIV-positive will be discontinued from the study and will be referred for care outside this study. HIV infection status will be determined using the Diagnosis of Lack of Infection in HIV-Exposed Children.
- ART exposure data by trimester of pregnancy must be available if ART exposed.
- Entry prior to birth through < 72 hours of age.
- Willingness of parent/legal guardian to provide written permission for child to participate in study.
- Willingness of biological mother to enroll at initial enrollment of her child.
Who cannot join
- Dynamic Cohort:
- None
Trial locations and contacts
22 sites in 2 countries.
22 sites in 2 countries
United States20 sites
University of Colorado Denver Health Sciences Center
Aurora, Colorado, 80045
University of Maryland
Baltimore, Maryland, 21201
University of Alabama
Birmingham, Alabama, 35294
SUNY Downstate Medical Center
Brooklyn, New York, 11203-2098
University of Illinois, Chicago
Chicago, Illinois, 60612
Ann and Robert H. Lurie Children's Hospital
Chicago, Illinois, 60614
Children's Diagnostic & Treatment Center
Fort Lauderdale, Florida, 33316
Baylor College of Medicine
Houston, Texas, 77030-3498
University of Florida Health Science Center
Jacksonville, Florida, 32209
University of California San Diego
La Jolla, California, 92093
University of Southern California
Los Angeles, California, 90033
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105-2764
University of Miami
Miami, Florida, 33136
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
New York University School of Medicine
New York, New York, 10016
Rutgers - New Jersey Medical School
Newark, New Jersey, 07101-1709
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
SUNY Stony Brook
Stony Brook, New York, 11794
Bronx Lebanon Hospital Center
The Bronx, New York, 10457
Jacobi Medical Center
The Bronx, New York, 10461
Puerto Rico2 sites
University of Puerto Rico Medical Center
San Juan, PR, 00935
San Juan Research Hospital
San Juan, 00936-8344
About this study
SMARTT will 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 of HIV-infected mothers.
Read the detailed description
Many antiretroviral therapy (ART) medications given to a pregnant woman cross the placenta and can be detected in the amniotic fluid and cord blood resulting in substantial fetal exposure. Therefore, there is concern about toxicity of the drugs in the fetus and infant. It is noteworthy that none of the currently approved ART medications for the prevention of maternal to fetal transmission of HIV are in Food and Drug Administration (FDA) Pregnancy Category A (no fetal risk ascertained in adequately controlled human studies). Thus, there is continued need to examine the toxicity of ART in HIV transmission prevention for the short-term toxicity of newer agents and combinations as well as the unanswered questions of longer term toxicity and subtle adverse effects.
The study will use a registry approach to conduct active surveillance among children < 12 years of age at enrollment. 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, growth, cardiac, neurologic, neurodevelopmental, behavior, language, and hearing. Clinical and laboratory data will be examined for abnormalities through a hierarchy of evaluations: adverse events (AE) will be identified → selected AEs will trigger predefined additional evaluations → significant observations will be defined as cases → a pattern of significant study-wide cases will be defined as signals. The incidence of these events of interest will be monitored over time and by ART regimen, and compared with historical data that may be suggestive of a signal. Some signals may be testable using existing and/or previously collected data, while other signals may indicate the need for additional hypothesis-driven studies outside of SMARTT.
The objectives of SMARTT are:
- To estimate the occurrence of potential ART-related toxicities through an ongoing surveillance system among HIV-uninfected children born to mothers with HIV infection with and without exposure to ART in utero and/or in the first two months of life and compare the occurrences of these outcomes with other sources of data as well as by ART exposures; and
- To actively encourage hypothesis-driven studies to confirm that the signals are due to ART exposure in utero and/or in the first two months of life. Note that the full design and execution of these studies may be beyond the scope of the SMARTT study but will be facilitated by SMARTT.
The specific aims of SMARTT are:
- To create a Static Surveillance Cohort to extend domain-specific data collection in children either 1) previously enrolled in any of the approved studies for enrollment into SMARTT; 2) previously enrolled in another pediatric HIV/AIDS cohort study with SMARTT Protocol Chair approval, or 3) not previously enrolled in an approved study but with equivalent data available in the medical record;
- To create a Dynamic Surveillance Cohort to examine domain-specific data of children newly exposed to ART in utero and/or in the first two months of life;
- To create a Young Adult Cohort to study long-term outcomes in SMARTT participants formerly enrolled in the Static and Dynamic cohorts.
- To identify a set of "triggers" for each domain that define a "signal" of possible ART toxicity and compare the occurrence of these signals with previously collected data and by ART exposure; and
- To encourage and facilitate the development of hypothesis-driven studies to evaluate whether a "signal" is the result of ART exposure in utero and/or in the first two months of life.
- Conditions
- Antiretroviral Toxicity
- Keywords
- Conditions and diagnoses potentially related to perinatal exposure to antiretroviral medications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Static Cohort- closed to enrollment and follow-up | HIV-uninfected children < 12 years of age at the time of enrollment, born of HIV-infected mothers | |
| Dynamic Cohort | HIV-uninfected children born of HIV-infected mothers enrolled from prior to birth through ≤ 72 hours of age | |
| Reference Cohort- closed to enrollment and follow-up | HIV-uninfected children born to a mother HIV uninfected at the time of the child's birth enrolled at 1, 3, 5, or 9 years of age(± 3 months) at the time of the study visit | |
| Young Adult Cohort- closed to enrollment and follow-up | Former Dynamic and Static Cohort participants ≥ 18 years of age. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurologic abnormalities
Assessed via head circumference measurement and medical record review for documented clinical diagnoses of seizures, microcephaly, or other neurologic diagnosis.
Measured: Annually birth through age 5; semiannual thereafter, assessments vary based on age of child.
Neurodevelopmental abnormalities
Assessed via the following neurodevelopmental tests: Bayley Screener, Bayley III, WPPSI-III, BASC-2, WASI, WISC-IV, BRIEF, WIAT II.
Measured: 1, 3, 5, 9, and 13 years of age, assessments vary based on age of child.
Abnormal growth and metabolic function
Assessed through the measurement of height, weight, tricep skinfold thickness, mid-upperarm circumference measurements, insulin and glucose, and fasting lipids.
Measured: Annually birth through age 5; semiannual thereafter, assessments vary based on age of child.
Cardiac abnormalities
Assessed through the administration of echocardiograms and serum biomarkers (ProBNP).
Measured: Ages 3-5.
Hearing dysfunction
Assessed via audiologic evaluation conducted by an audiologist.
Measured: At age 5 and for children of all ages meeting a hearing/language trigger.
Language dysfunction
Assessed via the following language tests: MCDI, Ages and Stages Communication Scale, PPVT IV, Goldman Fristoe 2, Rice Wexler, TELD-3, TOLD-3, Woodcock, CELF IV.
Measured: 1, 2, 3, 5, and 9 years of age, assessments vary based on age.
Drug Use and Sexual Activity
The assessment of sexual behavior and substance use will be 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.
Measured: 11, 13, 15, and 17 years of age.
Abnormal organ function
Assessed through the measurement of lipase, CPK, ALT, creatinine, glucose, LDH, BUN, WBC, PMN, lymphocytes, platelets, or hemoglobin ( ≥ Grade 3 adverse event).
Measured: Birth and age one, semiannual thereafter.
Death due to unknown medical condition
Assessed through autopsy review.
Measured: Annual.
Secondary outcomes (1)
Maternal substance use during pregnancy
Obtained via interview, toxicology report, and meconium testing.
Measured: Entry visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2011 (estimated)
- Study startMar 2007
- Primary completion31 May 2025
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (72)Papers the sponsor has linked to this study.
- Other trials for Antiretroviral ToxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5,169 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harvard School of Public Health (HSPH)
- Sponsor type
- University, hospital or other
- 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), National Institute of Mental Health (NIMH), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute of Neurological Disorders and Stroke (NINDS), Tulane University School of Medicine, National Institute of Dental and Craniofacial Research (NIDCR), NIH Office of AIDS Research (OAR)
- Responsible party
- Principal investigator, Paige Williams, Harvard School of Public Health (HSPH)
- Investigators
- Paige L Williams, Principal investigator, Harvard School of Public Health (HSPH)Ellen Chadwick, M.D., Principal investigator, Ann & Robert H Lurie Children's Hospital of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01310023
- Sponsor's protocol ID
- 1P01HD103133 - PH100
- Other IDs
- PH100, 1P01HD103133
- Acronym
- SMARTT
- Status last verified
- Jun 2025
- First submitted
- 4 Mar 2011
- Last updated
- 27 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Fulcher IR, Tchetgen Tchetgen EJ, Williams PL. Mediation Analysis for Censored Survival Data Under an Accelerated Failure Time Model. Epidemiology. 2017 Sep;28(5):660-666. doi: 10.1097/EDE.0000000000000687.
PubMed 28574921Correia K, Williams PL. Estimating the Relative Excess Risk Due to Interaction in Clustered-Data Settings. Am J Epidemiol. 2018 Nov 1;187(11):2470-2480. doi: 10.1093/aje/kwy154.
PubMed 30060004Correia K, Williams PL. A hierarchical modeling approach for assessing the safety of exposure to complex antiretroviral drug regimens during pregnancy. Stat Methods Med Res. 2019 Feb;28(2):599-612. doi: 10.1177/0962280217732597. Epub 2017 Oct 3.
PubMed 28969502Zash RM, Williams PL, Sibiude J, Lyall H, Kakkar F. Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges. Expert Opin Drug Saf. 2016 Nov;15(11):1501-1513. doi: 10.1080/14740338.2016.1226281. Epub 2016 Sep 6.
PubMed 27552003Bather JR, Horton NJ, Coull BA, Williams PL. The impact of correlated exposures and missing data on multiple informant models used to identify critical exposure windows. Stat Med. 2023 Apr 15;42(8):1171-1187. doi: 10.1002/sim.9664. Epub 2023 Jan 16.
PubMed 36647625Tassiopoulos K, Read JS, Brogly S, Rich K, Lester B, Spector SA, Yogev R, Seage GR 3rd. Substance use in HIV-Infected women during pregnancy: self-report versus meconium analysis. AIDS Behav. 2010 Dec;14(6):1269-78. doi: 10.1007/s10461-010-9705-0.
PubMed 20532607Griner R, Williams PL, Read JS, Seage GR 3rd, Crain M, Yogev R, Hazra R, Rich K; Pediatric HIV/AIDS Cohort Study. In utero and postnatal exposure to antiretrovirals among HIV-exposed but uninfected children in the United States. AIDS Patient Care STDS. 2011 Jul;25(7):385-94. doi: 10.1089/apc.2011.0068. Epub 2011 Jun 10.
PubMed 21992592Crain MJ, Williams PL, Griner R, Tassiopoulos K, Read JS, Mofenson LM, Rich KC; Pediatric HIVAIDS Cohort Study. Point-of-care capillary blood lactate measurements in human immunodeficiency virus-uninfected children with in utero exposure to human immunodeficiency virus and antiretroviral medications. Pediatr Infect Dis J. 2011 Dec;30(12):1069-74. doi: 10.1097/INF.0b013e318234c886.
PubMed 22051859Williams PL, Seage GR 3rd, Van Dyke RB, Siberry GK, Griner R, Tassiopoulos K, Yildirim C, Read JS, Huo Y, Hazra R, Jacobson DL, Mofenson LM, Rich K; Pediatric HIV/AIDS Cohort Study. A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers. Am J Epidemiol. 2012 May 1;175(9):950-61. doi: 10.1093/aje/kwr401. Epub 2012 Apr 6.
PubMed 22491086Siberry GK, Williams PL, Mendez H, Seage GR 3rd, Jacobson DL, Hazra R, Rich KC, Griner R, Tassiopoulos K, Kacanek D, Mofenson LM, Miller T, DiMeglio LA, Watts DH; Pediatric HIV/AIDS Cohort Study (PHACS). Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS. 2012 Jun 1;26(9):1151-9. doi: 10.1097/QAD.0b013e328352d135.
PubMed 22382151Watts DH, Williams PL, Kacanek D, Griner R, Rich K, Hazra R, Mofenson LM, Mendez HA; Pediatric HIV/AIDS Cohort Study. Combination antiretroviral use and preterm birth. J Infect Dis. 2013 Feb 15;207(4):612-21. doi: 10.1093/infdis/jis728. Epub 2012 Nov 29.
PubMed 23204173Wilkinson JD, Williams PL, Leister E, Zeldow B, Shearer WT, Colan SD, Siberry GK, Dooley LB, Scott GB, Rich KC, Lipshultz SE; Pediatric HIVAIDS Cohort Study (PHACS). Cardiac biomarkers in HIV-exposed uninfected children. AIDS. 2013 Apr 24;27(7):1099-108. doi: 10.1097/QAD.0b013e32835cf21c.
PubMed 23211773Sirois PA, Huo Y, Williams PL, Malee K, Garvie PA, Kammerer B, Rich K, Van Dyke RB, Nozyce ML; Pediatric HIVAIDS Cohort Study. Safety of perinatal exposure to antiretroviral medications: developmental outcomes in infants. Pediatr Infect Dis J. 2013 Jun;32(6):648-55. doi: 10.1097/INF.0b013e318284129a.
PubMed 23340561Himes SK, Scheidweiler KB, Tassiopoulos K, Kacanek D, Hazra R, Rich K, Huestis MA; Pediatric HIV/AIDS Cohort Study. Development and validation of the first liquid chromatography-tandem mass spectrometry assay for simultaneous quantification of multiple antiretrovirals in meconium. Anal Chem. 2013 Feb 5;85(3):1896-904. doi: 10.1021/ac303188j. Epub 2013 Jan 14.
PubMed 23256731Rice ML, Zeldow B, Siberry GK, Purswani M, Malee K, Hoffman HJ, Frederick T, Buchanan A, Sirois PA, Allison SM, Williams PL; Pediatric HIVAIDS Cohort Study (PHACS). Evaluation of risk for late language emergence after in utero antiretroviral drug exposure in HIV-exposed uninfected infants. Pediatr Infect Dis J. 2013 Oct;32(10):e406-13. doi: 10.1097/INF.0b013e31829b80ee.
PubMed 24067563
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surveillance Monitoring for ART Toxicities Study in HIV Uninfected Children Born to HIV Infected Women
- ClinicalTrials.gov ID
- NCT01310023
- Acronym / sponsor ID
- SMARTT / 1P01HD103133 - PH100
- Conditions
- Antiretroviral Toxicity
- Keywords
- Conditions and diagnoses potentially related to perinatal exposure to antiretroviral medications
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 5,169 participants (actual)
- Lead sponsor
- Harvard School of Public Health (HSPH)University, hospital or other
- 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), National Institute of Mental Health (NIMH), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute of Neurological Disorders and Stroke (NINDS), Tulane University School of Medicine, National Institute of Dental and Craniofacial Research (NIDCR), NIH Office of AIDS Research (OAR)
- Study start
- Mar 2007
- Primary completion
- 31 May 2025 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 7 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SMARTT will 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 of HIV-infected mothers.
Detailed description
Many antiretroviral therapy (ART) medications given to a pregnant woman cross the placenta and can be detected in the amniotic fluid and cord blood resulting in substantial fetal exposure. Therefore, there is concern about toxicity of the drugs in the fetus and infant. It is noteworthy that none of the currently approved ART medications for the prevention of maternal to fetal transmission of HIV are in Food and Drug Administration (FDA) Pregnancy Category A (no fetal risk ascertained in adequately controlled human studies). Thus, there is continued need to examine the toxicity of ART in HIV transmission prevention for the short-term toxicity of newer agents and combinations as well as the unanswered questions of longer term toxicity and subtle adverse effects.
The study will use a registry approach to conduct active surveillance among children < 12 years of age at enrollment. 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, growth, cardiac, neurologic, neurodevelopmental, behavior, language, and hearing. Clinical and laboratory data will be examined for abnormalities through a hierarchy of evaluations: adverse events (AE) will be identified → selected AEs will trigger predefined additional evaluations → significant observations will be defined as cases → a pattern of significant study-wide cases will be defined as signals. The incidence of these events of interest will be monitored over time and by ART regimen, and compared with historical data that may be suggestive of a signal. Some signals may be testable using existing and/or previously collected data, while other signals may indicate the need for additional hypothesis-driven studies outside of SMARTT.
The objectives of SMARTT are:
- To estimate the occurrence of potential ART-related toxicities through an ongoing surveillance system among HIV-uninfected children born to mothers with HIV infection with and without exposure to ART in utero and/or in the first two months of life and compare the occurrences of these outcomes with other sources of data as well as by ART exposures; and
- To actively encourage hypothesis-driven studies to confirm that the signals are due to ART exposure in utero and/or in the first two months of life. Note that the full design and execution of these studies may be beyond the scope of the SMARTT study but will be facilitated by SMARTT.
The specific aims of SMARTT are:
- To create a Static Surveillance Cohort to extend domain-specific data collection in children either 1) previously enrolled in any of the approved studies for enrollment into SMARTT; 2) previously enrolled in another pediatric HIV/AIDS cohort study with SMARTT Protocol Chair approval, or 3) not previously enrolled in an approved study but with equivalent data available in the medical record;
- To create a Dynamic Surveillance Cohort to examine domain-specific data of children newly exposed to ART in utero and/or in the first two months of life;
- To create a Young Adult Cohort to study long-term outcomes in SMARTT participants formerly enrolled in the Static and Dynamic cohorts.
- To identify a set of "triggers" for each domain that define a "signal" of possible ART toxicity and compare the occurrence of these signals with previously collected data and by ART exposure; and
- To encourage and facilitate the development of hypothesis-driven studies to evaluate whether a "signal" is the result of ART exposure in utero and/or in the first two months of life.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Static Cohort- closed to enrollment and follow-up | – | –HIV-uninfected children < 12 years of age at the time of enrollment, born of HIV-infected mothers |
| Dynamic Cohort | – | –HIV-uninfected children born of HIV-infected mothers enrolled from prior to birth through ≤ 72 hours of age |
| Reference Cohort- closed to enrollment and follow-up | – | –HIV-uninfected children born to a mother HIV uninfected at the time of the child's birth enrolled at 1, 3, 5, or 9 years of age(± 3 months) at the time of the study visit |
| Young Adult Cohort- closed to enrollment and follow-up | – | –Former Dynamic and Static Cohort participants ≥ 18 years of age. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children aged 0 - < 12 years born of HIV-infected mothers recruited from a clinical setting.
Key inclusion criteria (7 listed)
- HIV-exposed living fetus greater than or equal to 23 weeks gestation or a live infant born after 22 weeks gestation. Infants exposed and unexposed to ART will be enrolled.
- Any infant born of an HIV-infected mother may be enrolled pending determination of the infant's HIV infection status. However, infants found to be HIV-positive will be discontinued from the study and will be referred for care outside this study. HIV infection status will be determined using the Diagnosis of Lack of Infection in HIV-Exposed Children.
- ART exposure data by trimester of pregnancy must be available if ART exposed.
- Entry prior to birth through < 72 hours of age.
- Willingness of parent/legal guardian to provide written permission for child to participate in study.
Key exclusion criteria (2 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Neurologic abnormalities
Time frame: Annually birth through age 5; semiannual thereafter, assessments vary based on age of child.
Assessed via head circumference measurement and medical record review for documented clinical diagnoses of seizures, microcephaly, or other neurologic diagnosis.
Neurodevelopmental abnormalities
Time frame: 1, 3, 5, 9, and 13 years of age, assessments vary based on age of child.
Assessed via the following neurodevelopmental tests: Bayley Screener, Bayley III, WPPSI-III, BASC-2, WASI, WISC-IV, BRIEF, WIAT II.
Abnormal growth and metabolic function
Time frame: Annually birth through age 5; semiannual thereafter, assessments vary based on age of child.
Assessed through the measurement of height, weight, tricep skinfold thickness, mid-upperarm circumference measurements, insulin and glucose, and fasting lipids.
Cardiac abnormalities
Time frame: Ages 3-5.
Assessed through the administration of echocardiograms and serum biomarkers (ProBNP).
Hearing dysfunction
Time frame: At age 5 and for children of all ages meeting a hearing/language trigger.
Assessed via audiologic evaluation conducted by an audiologist.
Language dysfunction
Time frame: 1, 2, 3, 5, and 9 years of age, assessments vary based on age.
Assessed via the following language tests: MCDI, Ages and Stages Communication Scale, PPVT IV, Goldman Fristoe 2, Rice Wexler, TELD-3, TOLD-3, Woodcock, CELF IV.
Drug Use and Sexual Activity
Time frame: 11, 13, 15, and 17 years of age.
The assessment of sexual behavior and substance use will be 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.
Abnormal organ function
Time frame: Birth and age one, semiannual thereafter.
Assessed through the measurement of lipase, CPK, ALT, creatinine, glucose, LDH, BUN, WBC, PMN, lymphocytes, platelets, or hemoglobin ( ≥ Grade 3 adverse event).
Death due to unknown medical condition
Time frame: Annual.
Assessed through autopsy review.
1 secondary outcome
Maternal substance use during pregnancy
Time frame: Entry visit.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2025.
- Background: PubMed 28574921Fulcher IR, Tchetgen Tchetgen EJ, Williams PL. Mediation Analysis for Censored Survival Data Under an Accelerated Failure Time Model. Epidemiology. 2017 Sep;28(5):660-666. doi: 10.1097/EDE.0000000000000687.
- Background: PubMed 30060004Correia K, Williams PL. Estimating the Relative Excess Risk Due to Interaction in Clustered-Data Settings. Am J Epidemiol. 2018 Nov 1;187(11):2470-2480. doi: 10.1093/aje/kwy154.
- Background: PubMed 28969502Correia K, Williams PL. A hierarchical modeling approach for assessing the safety of exposure to complex antiretroviral drug regimens during pregnancy. Stat Methods Med Res. 2019 Feb;28(2):599-612. doi: 10.1177/0962280217732597. Epub 2017 Oct 3.
- Background: PubMed 27552003Zash RM, Williams PL, Sibiude J, Lyall H, Kakkar F. Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges. Expert Opin Drug Saf. 2016 Nov;15(11):1501-1513. doi: 10.1080/14740338.2016.1226281. Epub 2016 Sep 6.
- Background: PubMed 36647625Bather JR, Horton NJ, Coull BA, Williams PL. The impact of correlated exposures and missing data on multiple informant models used to identify critical exposure windows. Stat Med. 2023 Apr 15;42(8):1171-1187. doi: 10.1002/sim.9664. Epub 2023 Jan 16.
- Results publication: PubMed 20532607Tassiopoulos K, Read JS, Brogly S, Rich K, Lester B, Spector SA, Yogev R, Seage GR 3rd. Substance use in HIV-Infected women during pregnancy: self-report versus meconium analysis. AIDS Behav. 2010 Dec;14(6):1269-78. doi: 10.1007/s10461-010-9705-0.
- Results publication: PubMed 21992592Griner R, Williams PL, Read JS, Seage GR 3rd, Crain M, Yogev R, Hazra R, Rich K; Pediatric HIV/AIDS Cohort Study. In utero and postnatal exposure to antiretrovirals among HIV-exposed but uninfected children in the United States. AIDS Patient Care STDS. 2011 Jul;25(7):385-94. doi: 10.1089/apc.2011.0068. Epub 2011 Jun 10.
- Results publication: PubMed 22051859Crain MJ, Williams PL, Griner R, Tassiopoulos K, Read JS, Mofenson LM, Rich KC; Pediatric HIVAIDS Cohort Study. Point-of-care capillary blood lactate measurements in human immunodeficiency virus-uninfected children with in utero exposure to human immunodeficiency virus and antiretroviral medications. Pediatr Infect Dis J. 2011 Dec;30(12):1069-74. doi: 10.1097/INF.0b013e318234c886.
- Results publication: PubMed 22491086Williams PL, Seage GR 3rd, Van Dyke RB, Siberry GK, Griner R, Tassiopoulos K, Yildirim C, Read JS, Huo Y, Hazra R, Jacobson DL, Mofenson LM, Rich K; Pediatric HIV/AIDS Cohort Study. A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers. Am J Epidemiol. 2012 May 1;175(9):950-61. doi: 10.1093/aje/kwr401. Epub 2012 Apr 6.
- Results publication: PubMed 22382151Siberry GK, Williams PL, Mendez H, Seage GR 3rd, Jacobson DL, Hazra R, Rich KC, Griner R, Tassiopoulos K, Kacanek D, Mofenson LM, Miller T, DiMeglio LA, Watts DH; Pediatric HIV/AIDS Cohort Study (PHACS). Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS. 2012 Jun 1;26(9):1151-9. doi: 10.1097/QAD.0b013e328352d135.
- Results publication: PubMed 23204173Watts DH, Williams PL, Kacanek D, Griner R, Rich K, Hazra R, Mofenson LM, Mendez HA; Pediatric HIV/AIDS Cohort Study. Combination antiretroviral use and preterm birth. J Infect Dis. 2013 Feb 15;207(4):612-21. doi: 10.1093/infdis/jis728. Epub 2012 Nov 29.
- Results publication: PubMed 23211773Wilkinson JD, Williams PL, Leister E, Zeldow B, Shearer WT, Colan SD, Siberry GK, Dooley LB, Scott GB, Rich KC, Lipshultz SE; Pediatric HIVAIDS Cohort Study (PHACS). Cardiac biomarkers in HIV-exposed uninfected children. AIDS. 2013 Apr 24;27(7):1099-108. doi: 10.1097/QAD.0b013e32835cf21c.
- Pediatric HIV/AIDS Cohort StudyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paige L Williams principal investigator
Harvard School of Public Health (HSPH)
Ellen Chadwick, M.D. principal investigator
Ann & Robert H Lurie Children's Hospital of Chicago
22 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Antiretroviral Toxicity, run by Harvard School of Public Health (HSPH) at 22 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurologic abnormalities (time frame: Annually birth through age 5; semiannual thereafter, assessments vary based on age of child.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01310023, which also lists 72 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025; AzTrials last refreshed its copy on 8 Nov 2026.