25 Years of Prenatal HIV Drug Exposure Monitoring: Changing Times, but No Increased Risk of Birth Defects
An Interview With Vani Vannappagari, Ph.D., M.P.H.
The Antiretroviral Pregnancy Registry is a voluntary, observational, prospective study designed to collect data on pregnancy outcomes following prenatal exposure to antiretroviral drugs. In the history of the Registry, from January 1989 through July 2015, 16,699 live births with prenatal antiretroviral exposure have been reported. The overall prevalence of birth defects has not differed significantly from two population-based birth-defect surveillance systems.
The Registry, old news to HIV specialist providers, is now adapting to a changing HIV care landscape and the advent of treatment as prevention. To grow and provide more robust data, more providers must become aware of the Registry and enroll pregnant clients who are taking HIV medications -- either to manage HIV or to prevent its acquisition.
At AIDS 2016 in Durban, South Africa, I spoke with Vani Vannappagari, Ph.D., M.P.H., global head of epidemiology and real-world evidence for ViiV Healthcare and the industry co-chair for the Antiretroviral Pregnancy Registry Steering Committee, who shared her insights on the strengths and limitations of this unique data resource.
Welcome, Dr. Vannappagari. Would you please walk us through this poster? How does the Antiretroviral Pregnancy Registry work?
The Antiretroviral Pregnancy Registry started as the Zidovudine in Pregnancy Registry in 1989. That was to monitor for birth defects using the single drug that was first in the market. A few years later, with the addition of a few more drugs and other sponsors, it became the Antiretroviral Pregnancy Registry.
Currently, we monitor for 97 drugs: forty-seven brand-named, single-entity drugs and fixed-dose combinations and 50 generic versions of the drugs. All the manufacturers of the antiretrovirals who are marketing drugs in the U.S. are mandated to monitor for birth defects, most choose to join the Antiretroviral Pregnancy Registry to satisfy this requirement. The Registry is structured in such a way that there is a Sponsor Committee and an independent Scientific Advisory Committee. The Scientific Advisory Committee is currently made up of representatives from CDC [U.S. Centers for Disease Control and Prevention], NIH [U.S. National Institutes of Health], FDA [U.S. Food and Drug Administration] and U.S. Office of the Global AIDS Coordinator and Health Diplomacy; an advisor from the Elizabeth Glaser Pediatric AIDS Foundation; a patient advocate; and the academic obstetricians and researchers.
Then there is a coordinating center, which does the data collection and data analysis. The sponsoring companies don't receive the raw data. There is that level of separation to ensure the scientific integrity of the data is maintained.
The data is analyzed every six months and then the interim report is released. That report is available to the public via the Registry website. Any health care provider, any pregnant woman, or anyone interested in the safety of the drugs in pregnancy can read the report and, if there are any questions, contact the Registry with any questions.
What does it take for a newer HIV drug to become part of the Registry's data set?
All antiretroviral drugs can be monitored by the Registry. Participating sponsors register all of their marketed products and the Registry welcomes all manufacturers of antiretroviral products to join. Prospectively reported pregnancies, which means a pregnancy reported to the Registry before the outcome of the pregnancy is known, are the ones included in the primary analysis of the Registry.
There is a minimum threshold for the number of exposures. At least 200 first-trimester exposures are needed before we can do a meaningful analysis of the drug-related birth defect prevalence rate. As more data accrue on the newer drugs, they'll make it to the list. We will do more detailed analysis, and then you will start seeing them in the reports.
Reporting to the Registry is at the discretion of the provider, is that correct?
Yes; it's a voluntary reporting system by health care providers. The providers report all the exposures throughout the pregnancy, the pregnancy outcomes and the birth defects status.
What the Registry does not collect information on is the baby's HIV status. Because of confidentiality issues when the Registry was first set up, we didn't include collection of babies' HIV status as one of the things to report on. [In addition to] birth defects in the baby, prematurity, low birthweights, induced abortions, spontaneous abortions and stillbirths are the other things that we collect data on as part of the pregnancy outcome.
How do clients and providers acquire information about participating in the Registry and the opportunity to add to this pool of data?
A lot of health care providers in the HIV treatment arena already know about the Registry. But now, some patients living with HIV go back to their primary care providers once they are stabilized. And although the pregnant woman is taking antiretrovirals, she doesn't have to be HIV positive. If she's taking antiretrovirals for PrEP [pre-exposure prophylaxis] or PEP [post-exposure prophylaxis], she can ask the provider to report her case to the Registry.
One of our efforts is that we do a lot of awareness activities, presenting at many venues -- not just going to, for example, IAS [International AIDS Society conferences] or the HIV clinical meetings that are very focused on HIV health care providers. We also present data at other venues where OB/GYNs are the primary audience. The Women's Research Initiative, the FDA [U.S. Food and Drug Administration] and others have our information. We are trying to spread awareness.
Does the Registry differentiate at all between women who are living with HIV and those who are taking antiretrovirals for PrEP, or for other purposes?
Now, for Truvada [tenofovir/emtricitabine], for example, we have indication as to whether the drug was given for treatment purpose or for prophylaxis purpose. We are monitoring PrEP cases also. Those cases are now slowly accruing.
We have almost 300 HIV-negative pregnancies in the Registry that were exposed to antiretrovirals -- whether the pregnant patient is HIV uninfected or living with hepatitis B. Because some of the drugs that are being used for HIV treatment -- for example, tenofovir [Viread] and lamivudine [3TC, Epivir] -- are also used for treatment of hepatitis B. That's why we monitor those cases, whether they are coinfected with HIV, or monoinfected with hepatitis B, or taking medications for PrEP. All these cases can be, and should be, reported to the Pregnancy Registry.
Thank you very much. It was great talking to you.
This transcript has been lightly edited for clarity.
For additional information or to enroll a patient, please contact the Registry Coordinating Center by email at SM_APR@incresearch.com or by phone at 1-800-258-4263.