Research Team: Lena Serghides (principal investigator), Mona Loutfy, Kellie Murphy, Mark Yudin, Sharon Walmsley
What is this research about?
HIV-positive women who become pregnant may have a greater risk of certain complications, such as pre-term delivery and low birth weight infants, but the underlying reason for this elevated risk was not well understood. Pregnancy health depends on the development of a healthy placenta. One possible cause of these complications is that the development of the placenta and its blood supply is impaired by some of the antiretroviral drugs used by women living with HIV.
This research team undertook laboratory studies to better understand the role of HIV antiretroviral drugs in the development of the blood vessels that support the placenta. The team also followed two groups of women throughout their pregnancies (one group HIV-positive, the other HIV-negative) collecting blood samples from the mother, as well as samples of the placenta and cord blood at the time of delivery. These studies will help researchers to understand how antiretroviral drugs affect the placenta and may help physicians advise their patients about safer antiretroviral drug use during pregnancy.
Evidence from laboratory studies suggests that some types of protease inhibitor drugs (atazanavir, lopinavir, and ritonavir) reduce the amount of the sex hormone progesterone produced by the body, particularly in the third trimester of pregnancy. Conversely, other antiretroviral drugs such as NRTI and NNRTI drugs and at least one type of protease inhibitors (darunavir) do not appear to adversely affect progesterone producing cells. Studies of pregnant mice treated with ritonavir showed that exposure to the drug reduced the birth weight of newborn mice, and that progesterone supplements fed to the mice could partly reverse this effect. Similarly, by comparing the outcomes for a small group of HIV-positive and HIV-negative women, the researchers were able to show that women whose drug therapy contained protease inhibitors were more likely to have low progesterone levels, and those with low progesterone levels were more likely to have low birth weight babies. This research was published in the Journal of Infection Diseases in 2015, along with an editorial emphasizing these important findings.
These findings give important information to health care providers to advise their female patients about the safest forms of HIV antiretroviral treatment to use when pregnant or planning a pregnancy.
This project was supported by an OHTN grant of $300,000 to Dr. Lena Serghides in 2011, with extensions until 2016 to allow the completion of the project.