Pregnancy and Neonatal Outcomes following Prenatal Exposure to Cabotegravir: Data from The Antiretroviral Pregnancy Registry (APR) (215325)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Observational clinical cohort analysis

Study drug and medical condition

• Medicinal product name:
  VOCABRIA
• Study drug International non-proprietary name (INN) or common name:
  CABOTEGRAVIR
• Anatomical Therapeutic Chemical (ATC) code:
  (J05AX) Other antivirals

  Other antivirals
• Medical condition to be studied:
  Human immunodeficiency virus transmission

Population studied

• Short description of the study population:
  All pregnant women with any exposure to CAB at any time during the pregnancy or 12 months prior to the estimated conception period to account for long acting nature of CAB injectable, reported to the APR will be included in the analysis.
• Age groups:
  • Preterm newborn infants (0 – 27 days)
  • Term newborn infants (0 – 27 days)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  0

Study design details

• Study design:
  Non-interventional study
• Main study objective:
  • To describe maternal characteristics by timing of first exposure to CAB.; • To estimate frequency of birth defects among neonates, w/prenatal exposure to CAB, by timing of first exposure.; • To estimate frequency of non-defect adverse pregnancy and neonatal outcomes, by timing of first exposure
• Setting:
  The APR (“Registry”) is a voluntary, international, prospective exposure registration cohort that was established in 1989 to monitor and detect any teratogenic effects of ARV drugs used in pregnancy. Although the APR is an international registry with case reports from 70 countries, the majority (73%) of the case reports are from the US and its territories. Each year the Registry enrolls approximately 1300-1700 pregnant women exposed to ARV drugs. This number represents approximately 25% of the 5,000 HIV positive women who give birth to live infants annually in the United States and approximately 350 pregnant women from other countries.
• Comparators:
  There is no direct comparator arm used in this study and hence no formal sample size estimations are performed. Data from external sources like MACDP, TBDR, the prevalence rates from the APR and EUROCAT (European network of population-based registries for the epidemiological surveillance of congenital anomalies) will be used as ; reference values for background birth defect rates to put the findings from this study in context.
• Outcomes:
  • Demographic, clinical and immunological characteristics, co-infections, timing of CAB LA initiation, other ARVs used in the regimen ; • Number of participants with live births, induced or spontaneous abortion, or stillbirth ; • Number of neonates with low/very low/extremely low birth weight ; • Number of infants with preterm birth or severe preterm birth ; • Incidence of birth defects
• Data analysis plan:
  Four analyses will be conducted: the first analyses when the number of pregnant women exposed to CAB containing regimen during first trimester in the cohort reaches 25, followed by two more analyses when the study population reaches 100 and 200 pregnancies with first trimester exposures to CAB. A final analysis will be done 12 months after the 3rd analysis. This analysis will be descriptive in nature. Demographic and clinical characteristics of the pregnant women will be tabulated. Frequency assessment of birth defects will be done among all live births. Only singleton births will be included in the analysis of non-defect outcomes, multiple births such as twin and triplet births will be excluded due to the increased risk of adverse outcomes associated with such pregnancies.