AEGiS-Glasgow [1758-2652-11-S1-O22] ANTIRETROVIRAL PREGNANCY REGISTRY (APR) AT 10,000 PROSPECTIVE REPORTS

Ninth International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 9-13 November 2008

ANTIRETROVIRAL PREGNANCY REGISTRY (APR) AT 10,000 PROSPECTIVE REPORTS

J Int AIDS Soc 2008, 11(Suppl 1):22 doi:10.1186/1758-2652-11-S1-O22

KP Beckerman¹, D Covington², K Dominguez³, A Scheuerle⁴, VX Vannappagari⁵, DH Watts⁶ and H Tilson⁷
¹ Albert Einstein College of Medicine, Bronx, New York, USA ² Kendle International Inc, Wilmington, North Carolina, USA ³ Centers for Disease Control, Atlanta, Georgia, USA ⁴ Tesserae Genetics, Dallas, Texas ⁵ Glaxo Smith Kline, New Jersey, USA ⁶ National Institute of Child Health and Human Development, Bethesda, Maryland, USA ⁷ University of North Carolina School of Public Health, Chapel Hill, North Carolina, USA

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 1^st trimester (TRI) exposure (when organogenesis occurs), vs. 2^nd and 3^rd 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 1^st TRI exposures. These reports allow detection of a potential 1.5-fold increase in overall anomalies following 1^st TRI exposure to any ARV compared to 2^nd/3^rd TRI exposures. We found no such increase. Birth defect prevalence after any 1^st TRI ARV exposure was 3.0% vs. 2.6% following any 2^nd/3^rd TRI ARV exposure (1.13 relative risk, 95% CI = 0.89, 1.43). Twelve individual drugs have >200 1^st TRI reports and allow us to detect a potential 1.5–2-fold

Table 1 (abstract P22)

	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%)

increase in all defects for each agent (Table 1). Such an increase has not been found. 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].

CONCLUSIONS: 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.

REFERENCES:

Watts DH, et al: Assessment of birth defects according to maternal therapy among infants in the Women and Infants Transmission Study. J Acquir Immune Defic Syndr. 2007 Mar 1;44(3):299-305.
Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989 through 31 January 2008. Wilmington, NC: Registry Coordinating Center; 2008 [http://www.APRegistry.com].

2008-11-10
1758-2652-11-S1-O22

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