No increased risk of birth defects with darunavir: findings from the Antiretroviral Pregnancy Registry

Polly Clayden, HIV i-Base

The Antiretroviral Pregnancy Registry (APR) found no apparent increase in the frequency of specific birth defects with first trimester darunavir (DRV) exposure. These findings were presented at the 6th International Workshop on HIV and Women.

DRV has recently been added to the US pregnancy guidelines list of preferred antiretrovirals for the treatment of women during pregnancy.

Preclinical DRV studies showed no embryotoxicity or teratogenicity in animal models. Human pregnancy studies have focused on pharmacokinetics.

The APR is designed to identify teratogenetic signals in infants exposed to maternal antiretrovirals. The registry receives reports of women taking antiretrovirals in pregnancy, their pregnancies are followed and the outcomes recorded. Reporting is voluntary.

Data from approximately 1300 pregnant women from the US (15% of the 8,700 HIV positive pregnant women who give birth each year worldwide) and 200 women from other countries are reported to the APR annually.

The analysis presented was conducted to evaluate: birth outcomes for ART regimens including and not including DRV; prevalence of birth defects for regimens including DRV; and prevalence for regimens including other protease inhibitors (PI) by earliest trimester of exposure.

The analysis included data from 17,332 women: 535 received ART regimens containing DRV and 16,797 ART regimens excluding DRV.

The women were a median age of 28 years (range 13-55), 57% black and 18% Hispanic and 15% white. CD4 count at the start of pregnancy among women with available data were: 17% <200 cells/mm3, 48% 200-499 cells/mm3 and 35% > 500.

Of 17,330 birth outcomes, 542 were exposed to DRV and 17,088 were not. There were no differences in still births, induced abortion and preterm birth among women exposed or not exposed to DRV. There was increased risk of spontaneous losses and low birth rate: relative risk (RR) 1.60 (95% CI 1.05-2.44), p=0.0348, and RR 1.39 (95% CI 1.10-1.76), p=0.008, respectively.

The overall prevalence of birth defects with DRV exposure was 2.81% (14 out of 498 live births) and without DRV exposure 2.8.6% (456 out of 15, 930 live births), RR 0.98 (95% CI 0.57-1.68), p=1.0.

The prevalence of birth defects in pregnancies with first trimester exposure to a PI was 2.89% (122 defects out of 4,224 live births) and with second or third trimester exposure the prevalence was 2.95% (168 birth defects out of 5,703 live births).

For DRV, the relative risk of birth defects with earliest exposure during the first trimester of pregnancy vs the second or third trimester was 1.75 (95% CI 0.47-6.55), p=0.55.

Comment

The authors noted that one of the limitations of this analysis is the small number of women in the APR who used DRV-containing regimens – the threshold for detection of birth defects is 200 cases.

They also added that the analysis is not adjusted for maternal age, CD4 count or HIV clinical category and the groups receiving regimens including and excluding DRV were different sizes.

Another limitation was the lack of information on any previous exposure to antiretrovirals earlier in pregnancy for women starting a PI in the second or third trimesters.

Other limitations are similar to any voluntary reporting to a registry: differences in reporting, different assessments of birth defects and loss to follow up, as well as possible under reporting of women with early terminations or losses.

Nevertheless it is important that doctors caring for HIV positive pregnant women report to the APR – particularly outside the US, which still contributes the majority of the data and that from other countries remains scarcer.

Reference:

Short WR et al. Use of antiretroviral regimens including darunavir during pregnancy: findings from the Antiretroviral Pregnancy Resistry. 6th International Workshop on HIV & Women. 20-21 February 2016. Boston. Poster abstract 23.