by Nayaab Punjani

Graphic design by Anne Catalina McGrath

According to the World Health Organization (WHO), 39 million people are living with human immunodeficiency virus (HIV).¹ HIV causes weakening of the immune system through progressive loss of white blood cells, leaving patients susceptible to other infectious conditions like tuberculosis.² Anti-retroviral (ARV) therapy (ART) has revolutionized patient care through drugs such as integrase strand transferase inhibitors and protease inhibitors, which inhibit the virus’ replication cycle, and reduce the amount of virus within the body (known as “viral load”). In addition to alleviating patient’s symptoms, these drugs also limit transmission to one’s sexual partner. For pregnant women living with HIV, ARVs improve maternal health and prevent transmission of HIV to the fetus, although they have been associated with pre-term births, as well as placental and metabolic changes. New drugs continue to be developed for HIV, however pregnancy relevant safety data often lags decades behind and is reliant on researchers to acquire. There is a need to better understand the nature of how ARVs change the in utero environment and the impacts post-birth for children who are HIV-uninfected and ARV-exposed.

“…it is our duty as HIV researchers to meaningfully involve people living with HIV in all steps of our research.”

-Dr. Lena Serghides

Dr. Lena Serghides, a senior scientist and principal investigator at the Toronto General Hospital Research Institute (TGHRI), studies the effects of ART on pregnant women and the developmental outcomes of their children. Dr. Serghides did not follow a typical research path. Switching from business school to a PhD initially in the malaria field, her postdoctoral fellowship was the first time she began exploring HIV research by examining malaria HIV co-infection in pregnant women. With an interest in HIV and pregnancy, Dr. Serghides consulted HIV community members and found that their primary concern was not how HIV was affecting their pregnancies, but instead how ARV drugs were affecting their babies. Dr. Serghides explains, “each year approximately 1.5 million women with HIV become pregnant and most of these pregnancies are exposed to HIV antiretrovirals. This means that close to 1.2 million children are born HIV/ARV exposed uninfected each year.  This makes these children the fastest rising HIV affected population and not much work is being done to understand how their in utero exposures affect their long term health, and to make sure that these kids meet their full potential.” Dr. Serghides also highlights the importance of patient engagement in her research, as “the whole HIV movement was driven by the HIV community”, prompting research and funding to be put towards drugs to treat HIV. “Greater involvement and meaningful engagement of people living with HIV is a foundation for the HIV movement and it is our duty as HIV researchers to meaningfully involve people living with HIV in all steps of our research.”

Dr. Serghides’ early research focused on hormonal dysregulation in pregnancy by protease inhibitor ARV drugs, whereby a decrease in progesterone and increase in oestradiol was observed.³ Using a mouse model developed in her lab, they found that providing progesterone supplementation early during pregnancy helped recover some of the fetal growth restriction and placental vasculature changes observed following protease inhibitor exposure. This prompted her lab to conduct a progesterone supplementation trial, although the low number of available participants in Toronto prevented the trial from being feasible. In a comparable trial in Zambia, however, progesterone supplementation was found to improve pregnancy outcomes in women taking protease inhibitors.⁴ 

A lot of Dr. Serghides’ work looks at examining the “morphometry and morphology of the placenta and how it relates to fetal outcomes.” She has a current Canadian Institutes of Health Research (CIHR)-funded international collaboration, working with Drs. Lisa Bebell and Clive Gray, to recruit pregnant women in Toronto, Uganda, and South Africa. This study will allow the team to directly compare differences in placental structure, vascularization, and nutrient transport taking into consideration the types of ARV therapies available globally. 

Moving beyond the in utero placental changes, Dr. Serghides is also in the process of recruiting children born to mothers living with HIV, to examine the impact of the ARV–associated placental, hormonal, and immune changes on their neurodevelopment. This CIHR-funded study is also being paralleled with studies done in the mouse model, providing a controlled experimental comparison that is not influenced by other factors such as socioeconomic status and environment, which can tie into some of the developmental differences observed clinically. 

In addition to her research, Dr. Serghides is part of the Canadian Infant Feeding in HIV network. As part of a CIHR funded dissemination grant she helped organize workshops at HIV service organizations across Ontario to provide information that would facilitate conversations about infant feeding choices for women living with HIV. Formula feeding is recommended for all women living with HIV and in Ontario, formula is provided free for one year. However some women living with HIV are considering breastfeeding due to various cultural, emotional, and health factors. It is important that all women are provided with the information needed to make their own informed decision on infant feeding choices. Thus, these workshops ensured that front line staff can educate new parents about the risk of HIV transmission through breastmilk and ways to minimize it, such as maintaining ART. An informational video developed by Dr. Serghides and Sarah Crawley, a graduate of the Biomedical Communications Program, explaining the associated risks of HIV transmission during breastfeeding won the CIHR 2019 Institute of Human Development, Child and Youth Health (IHDCYH) Talks video competition.⁵ 

There is still a lot of stigma surrounding HIV, and a continued fear of transmission. However, Dr. Serghides emphasizes that “research has shown us that if people take their antiretrovirals and their viral load is undetectable then the chance of transmission to a sexual partner is zero.” Furthermore, “good data are available showing that if women come into a pregnancy already on antiretrovirals and with an undetectable viral load the chance of transmitting HIV to their baby during pregnancy is again zero.”

Dr. Serghides wants the public to understand that “these drugs have revolutionized HIV. HIV is now a manageable chronic ailment and people with HIV are living normal lives with a lifespan that is similar to the general population. Women living with HIV wishing to have a baby can do so without fear that they are going to transmit HIV to their baby as long as they are well-treated.” It is exciting to see the evolution of new therapies becoming available such as long-term injectables which allow people living with HIV to take a drug injection every few months rather than take a pill every day. Research will be ongoing in tandem to continue to test the safety of these new ARV drugs in pregnancy through mixed clinical and basic science models, to be able to provide the best possible care to mothers living with HIV and their children. 

References

1. HIV [Internet]. [cited 2023 Aug 22]. Available from: https://www.who.int/data/gho/data/themes/hiv-aids
2. HIV and AIDS [Internet]. [cited 2023 Aug 22]. Available from: https://www.who.int/news-room/fact-sheets/detail/hiv-aids
3. Dunk CE, Serghides L. Protease inhibitor-based antiretroviral therapy in pregnancy: effects on hormones, placenta, and decidua. The Lancet HIV. 2022 Feb 1;9(2):e120–9. 
4. Conner MG, Vwalika B, Freeman BL, et al. Effect of weekly 17-hydroxyprogesterone caproate on small for gestational age among pregnant women with HIV in Zambia. AIDS. 2022 Nov 15;36(14):2079–81. 
5. “Winner IHDCYH Talks 2019: HIV transmission through breastfeeding” Youtube, IHDCYH Talks, Nov 1 2019. https://www.youtube.com/watch?v=n7sRKeUTmeE