Volume 11 Supplement 1

Abstracts of the Ninth International Congress on Drug Therapy in HIV Infection

Open Access

O223 Antiretroviral Pregnancy Registry (APR) at 10,000 prospective reports

  • KP Beckerman1,
  • D Covington2,
  • K Dominguez3,
  • A Scheuerle4,
  • VX Vannappagari5,
  • DH Watts6 and
  • H Tilson7
Journal of the International AIDS Society200811(Suppl 1):O22

https://doi.org/10.1186/1758-2652-11-S1-O22

Published: 10 November 2008

Background

Prospective data on neonatal outcome following in utero exposure to antirerovirals (ARVs) are essential components of safety monitoring of these life-saving therapies. Toward this end, APR was created in 1989 and is now one of the largest ongoing pregnancy registries in the world.

Methods

APR is an international registry that uses a prospective exposure-registration cohort design to monitor potential birth defects following in utero ARV exposure. Health care providers voluntarily enroll exposed pregnant women, then provide follow-up neonatal data. We analyzed APR data for their ability to detect, at 80% power with Type I error rate of 5%, potential increases in birth defect prevalence following fetal 1st trimester (TRI) exposure (when organogenesis occurs), vs. 2nd and 3rd TRI exposures.

Summary of results

By January 2008, APR received 11,209 prospective reports. Of these, 9,400 live birth (LB) outcomes were available, including 3,951 LB following 1st TRI exposures. These reports allow detection of a potential 1.5-fold increase in overall anomalies following 1st TRI exposure to any ARV compared to 2nd/3rd TRI exposures. We found no such increase. Birth defect prevalence after any 1st TRI ARV exposure was 3.0% vs. 2.6% following any 2nd/3rd TRI ARV exposure (1.13 relative risk, 95% CI = 0.89, 1.43). Twelve individual drugs have >200 1st TRI reports and allow us to detect a potential 1.5–2-fold increase in all defects for each agent (Table 1). Such an increase has not been found.

Table 1

 

Defects

LB Prevalence (95%CI)

Zidovudine

87/2808

3.1% (2.5%,3.8%)

Lamivudine

85/2784

3.1% (2.4%,3.8%)

Nelfinavir

33/972

3.4% (2.3%,4.7%)

Nevirapine

18/737

2.4% (1.5%,3.8%)

Stavudine

19/651

2.9% (1.8%,4.5%)

Ritonavir

16/628

2.5% (1.5%,4.1%)

Abacavir

17/512

3.3% (1.9%,5.3%)

Tenofovir

11/491

2.2% (1.1%,4.0%)

Efavirenz

10/364

2.7% (1.3%,5.0%)

Didanosine

16/353

4.5% (2.6%,7.3%)

Lopinavir

6/328

1.8% (0.7%,3.9%)

Indinavir

6/272

2.2% (0.8%,4.7%)

Two drugs met the threshold for evaluation and further monitoring: zidovudine was associated with an increased risk of hypospadius [1], and a higher than expected defect prevalence following didanosine exposure that has no apparent pattern and is not statistically significant [2].

Conclusion

In summary, prospectively collected APR data have not detected an overall increase in birth defects following in utero ARV exposure during organogenesis. We continue to follow two trends that do not reach statistical significance.

Authors’ Affiliations

(1)
Albert Einstein College of Medicine, Bronx
(2)
Kendle International Inc
(3)
Centers for Disease Control
(4)
Tesserae Genetics
(5)
Glaxo Smith Kline
(6)
National Institute of Child Health and Human Development
(7)
University of North Carolina School of Public Health

References

  1. Watts DH, et al: Assessment of birth defects according to maternal therapy among infants in the Women and Infants Transmission Study. Journal of Acquired Immune Deficiency Syndromes: JAIDS. 2007, 44 (3): 299-305. 10.1097/QAI.0b013e31802e2229.PubMedView ArticleGoogle Scholar
  2. Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989 through 31 January 2008. 2008, Wilmington, NC: Registry Coordinating Center, [http://www.APRegistry.com]

Copyright

© Beckerman et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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