Аnalysis of cases of adverse reactions during the use of antiretroviral therapy in pregnant women

Antiretroviral therapy is a treatment that involves the regular use of a combination of antiviral drugs. During pregnancy, women with human immunodeficiency virus (HIV) do not stop antiretroviral treatment, as this is necessary to reduce the risk of HIV transmission from the mother to the fetus. However, the body of a pregnant woman can affect the way the antiretroviral medications work, called their pharmacokinetics and pharmacodynamics. This can increase the risk of adverse drug reactions (ADR) from the medications.

The aim of the study was investigated of the frequency of ADR of antiretroviral therapies based on analysis of spontaneous reports of ADR among pregnant women who were registered in the ARCADe regional database (Adverse Reactions in Crimea, Autonomous Database). 

Materials and methods. The study included 64 spontaneous ADR reports registered in the electronic database of spontaneous ARCADE messages in the Republic of Crimea between January 1, 2012 and December 31, 2021. These reports were collected from pregnant women who were taking ARP.

Results and discussion. The most common types of ADR have been reported when using combined antiretroviral medications and nucleoside reverse transcriptase inhibitor drugs. The combination of lamivudine and zidovudine drugs was the most frequent cause of adverse effects among pregnant women on antiretroviral therapy. Hematopoietic disorders and dyspepsia were the most prevalent clinical manifestations of the ADR. Almost 85% of identified ADR required medication adjustment, although only 5% were classified as severe manifestations of the events.

Conclusion. Long-term antiretroviral drug use requires regular monitoring of ADR, particularly during pregnancy, to provide timely care and maintain high levels of patient adherence to an effective antiretroviral treatment regimen. Despite the high incidence of anemia, skin, and dyspeptic problems, the proportion of serious ADR was found to be relatively low, which justifies the use of antiretroviral therapy during pregnancy. This justifies the continued use of antiretroviral therapy during pregnancy, as it has undeniable benefits in preventing transmission of HIV from mother to child, suppressing viral replication, and reducing mortality in infants.

1. Resolution No. 1 of the Chief State Sanitary Doctor of the Russian Federation dated January 11, 2011 «On approval of Sanitary Rules 3.1.5.2826-10 «Prevention of HIV infection». Moscow, 2011. (In Russ.)]. URL: https://www.garant.ru/products/ipo/prime/doc/12084824.

2. Sokolova T.N., Kasparova A.E., Kovalenko L.V. et al. Course of HIV infection and mechanisms of pregnancy failure development in women living in the Subarctic region. Ulyanovsk Medical and Biological Journal, 2020, No. 2, рр. 57–69 (In Russ.)]. doi: 10.34014/2227-1848-2020-2-57-69.

3. Specialized Scientific Research Department for the prevention and control of AIDS. HIV infection. Newsletter No. 47. Moscow, 2023 (In Russ.)]. http://www.hivrussia.info/wp-content/uploads/2023/05/Byulleten-47-VICH-infektsiya-za-2021-g.pdf.

4. The Ministry of Health of the Russian Federation. Clinical recommendations «HIV infection in pregnant women». Moscow, 2021 (In Russ.)]. URL: https://cr.minzdrav.gov.ru/schema/717_1.

5. Eggleton J.S., Nagalli S. Highly Active Antiretroviral Therapy (HAART) // StatPearls. Treasure Island (FL). StatPearls Publishing; July 3, 2023. URL: https://www.ncbi.nlm.nih.gov/books/NBK554533.

6. Boyd S.D., Sampson M.R., Viswanathan P. et al. Cobicistat-containing antiretroviral regimens are not recommended during pregnancy: viewpoint // AIDS. 2019. Vol. 33, No. 6. Р. 1089–1093. doi: 10.1097/QAD.0000000000002163.

7. Bikmukhametov D.A. The influence of individual characteristics of an HIV-infected patient on adherence to antiretroviral therapy: specialty 14.00.10: abstract of the dissertation for the degree of Candidate of Medical Sciences / Bikmukhametov Damir Amirovich. Kazan, 2007. 23 p. (In Russ.)]. URL: https://elibrary.ru/njctlf.

8. Vasilevsky I.V. Gestational safety in the pharmacotherapy of HIV infection in pregnant women: the position of a clinical pharmacologist. Current issues of HIV infection: Proceedings of the International Scientific and Practical Conference, St. Petersburg, June 10–11, 2019. St. Petersburg: St. Petersburg public organization «Human and his health», 2019, рр. 235–237 (In Russ.)]. URL: https://elibrary.ru/mwaqrh.

9. Kevra M.K., Khapalyuk A.V., Gavrilenko L.N. et al. Clinical pharmacology: a textbook / ed. by M. K. Kevr. Minsk: Higher School, 2015. 575 p. (In Russ.)]. ISBN 978-985-06-2454-3.

10. Pariente G., Leibson T., Carls A. et al. Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review // PLoS Med. 2016. Vol. 13, No. 11. e1002160. doi: 10.1371/journal.pmed.1002160.

11. Lamorde M., Wang X., Neary M. et al. Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum // Clin. Infect. Dis. 2018. Vol. 67, No. 5. Р. 785–790. doi: 10.1093/cid/ciy161.

12. Chilaka V.N., Konje J.C. HIV in pregnancy — An update // Eur. J. Obstet. Gynecol. Reprod. Biol. 2021. Vol. 256. Р. 484–491. doi: 10.1016/j.ejogrb.2020.11.034.

13. Rukmangathen R., Brahmanapalli V.D., Thammisetty D.P. et al. Study of adverse drug reactions to antiretroviral therapy in a tertiary care hospital, Tirupati // Perspect. Clin. Res. 2020. Vol. 11, No. 4. Р. 158–163. doi: 10.4103/picr.PICR_133_18.

14. Phoswa W.N., Naicker T., Ramsuran V., Moodley J. The Role of Highly Active Antiretroviral Therapy (HAART) on Interleukin 17A (IL-17A) in Normotensive and Preeclamptic Black South African Women // Infect. Dis. Obstet. Gynecol. 2020. Vol. 2020. Р. 3417632. doi: 10.1155/2020/3417632.

15. Yu Sh G., Yuones H., Elena B., Omar A.B., Hadi N.R., Ahmad A.H. Features of HIV/AIDS pharmacotherapy in pregnant women // Wiad Lek. 2021. Vol. 74, No. 12. Р. 3226–3229. doi: 10.36740/WLek202112118.

16. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission. World Health Organization. 2022. URL: https://clinicalinfo.hiv.gov/en/guidelines/perinatal/guidelines-panel-members?view=full.

17. Office of Infectious Disease and HIV/AIDS Policy. The Antiretroviral Pregnancy Registry. Wilmington. 2024. URL: https://clinicalinfo.hiv.gov/en/guidelines/perinatal/safety-toxicity-arv-agents-pregnancy-registry

18. European AIDS Clinical Society, EACS). 2023. URL: https://www.eacsociety.org/media/guidelines-12.0_ru.pdf.

19. Pinheiro E.A., Stika C.S. Drugs in pregnancy: Pharmacologic and physiologic changes that affect clinical care // Semin Perinatol. 2020. Vol. 44, No. 3. Р. 151221. doi: 10.1016/j.semperi.2020.151221.

20. Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants: Recommendations for a Public Health Approach: 2010 Version. Geneva: World Health Organization; 2010. URL: https://www.ncbi.nlm.nih.gov/books/NBK304944.

21. Phillips T., Cois A., Remien R.H. et al. Self-Reported Side Effects and Adherence to Antiretroviral Therapy in HIV-Infected Pregnant Women under Option B+: A Prospective Study // PLoS One. 2016. Vol. 11, No. 10. Р. e0163079. doi: 10.1371/journal.pone.0163079.

22. Zuk D.M., Hughes C.A., Foisy M.M. et al. Adverse effects of antiretrovirals in HIV-infected pregnant women // Ann. Pharmacother. 2009. Vol. 43, No. 6. Р. 1028–1035. doi: 10.1345/aph.1L689.

23. Joseph N.T., Satten G.A., Williams R.E. et al. The Effect of Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus (HIV)-1 in Pregnancy on Gestational Weight Gain // Clin. Infect. Dis. 2022. Vol. 75, No. 4. Р. 665–672. doi: 10.1093/cid/ciab994.