January 2015 

Good news about HIV drug safety from an even larger study

The largest database that has captured information on the safety of ART used during pregnancy is the Antiviral Pregnancy Registry (herein after called the Registry). This database conducts observational, or cohort, analyses. The Registry is located in the U.S. and although about 78% of its cases are from the U.S., it also collects information from 67 other countries, including Canada, Brazil and countries in Europe and Southern Africa. Scientists with the Registry have analysed information collected between 1989 and 2014. Out of 16,646 evaluable reports sent to the Registry, 7,135 were cases in which the fetus was exposed to ART during the first trimester of pregnancy.

Researchers with the Registry made the following statement:

“For the overall population exposed to antiretroviral drugs in this Registry, no increases in risk of overall birth defects or specific defects have been detected to date.”

This is very reassuring news for HIV-positive mothers and their healthcare providers.

Focus on two older drugs

The Registry has data on so many pregnancies and infants that it has the statistical power to detect the potential association of many individual drugs used in HIV regimens with birth defects. The vast majority of drugs used by HIV-positive women were not found to have any association with an increased risk for birth defects. However, there were two notable exceptions, as follows:

  • ddI (didanosine, Videx EC)
  • nelfivinavir (Viracept)

The rate of infants with birth defects possibly due to exposure to these drugs was approximately 2.9%. This is in comparison to a rate of 2.7% in another database. Researchers with the Registry described this increase (from 2.7% to 2.9%) in birth defects among mothers who used these drugs to be “modest.” They stated that “no pattern of birth defects has been detected” with fetal exposure to ddI and nelfinavir, and they are not certain that the “modest” increase in birth defect rates with these drugs has any clinical relevance.

Today in Canada and other high-income countries, doctors do not routinely prescribe ddI and/or nelfinavir, as there are safer and more effective drugs from which they can choose when caring for all HIV-positive people, including pregnant women.

Screening many drugs

Due to the high number of participants enrolled, the Registry has the ability to detect the possibility of “at least a two-fold increase in the risk of overall birth defects” associated with exposure in the womb during the first trimester of pregnancy to the following drugs:

  • abacavir (Ziagen, and in Kivexa, Trizivir and Triumeq)
  • atazanavir (Reyataz)
  • darunavir (Prezista and in Prezcobix)
  • didanosine (ddI, Videx)
  • efavirenz (Sustiva, Stocrin and in Atripla)
  • indinavir (Crixivan)
  • stavudine (d4T, Zerit)

However, no increased signal of risk was detected.

The Registry is also able to detect the possibility of “at least a 1.5-fold increased risk” of overall birth defects” associated with exposure in the womb during the first trimester to the following drugs:

  • FTC (emtricitabine and in Emtriva, Truvada, Atripla, Complera and Stribild)
  • 3TC (lamivudine and in Combivir, Trizivir, Ziagen and Triumeq)
  • tenofovir (Viread and in Truvada, Atripla, Complera and Stribild)
  • lopinavir (in Kaletra)
  • AZT (zidovudine, Retrovir and in Combivir and Trizivir)

With the exception of AZT, the Registry did not find any possible signal of increased risk for birth defects.

Regarding AZT

Given this initial safety signal with AZT, the Registry then further investigated the possible association of exposure to AZT in the womb with defects in the male genitals of infants. Here is their statement about this:

“The Registry concludes that the data do not support a causal relationship between Zidovudine and/or lamivudine exposure and [birth defects affecting male genitals]. The disappearance of the [increased risk] in more sophisticated analyses suggests that the increase may be related to other factors.”

Researchers with the Registry are continuing to be vigilant about the impact of AZT and other drugs on the health of the fetus, and, as data accumulates, will issue additional reports. Our next story deals with other factors that may play a role in hypospadias.


We thank infectious disease specialist Jason Brophy, MD, for his helpful comments, expert review and research assistance.

—Sean R. Hosein


  1. Williams PL, Crain MJ, Yildirim C, et al. Congenital anomalies and in utero antiretroviral exposure in human immunodeficiency virus-exposed uninfected infants. JAMA Pediatrics. 2014; in press.
  2. Chou R, Cantor AG, Zakher B, et al. Screening for HIV in pregnant women: systematic review to update the 2005 U.S. Preventive Services Task Force recommendation.  Annals of Internal Medicine. 2012 Nov 20;157(10):719-28.
  3. National Institutes of Health. NIH-sponsored study identifies superior drug regimen for preventing mother-to-child HIV transmission. Press release. 17 November 2014. Available at:
  4. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989 through 31 January 2014. Wilmington, NC: Registry Coordinating Center; 2014. Available at: [accessed 19 November 2014]