Vol 90, No 7 (2019)
Research paper
Published online: 2019-07-26
Exposure to dolutegravir in pregnant women living with HIV in Central and Eastern Europe and neighboring countries — data from the ECEE Network Group
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, 2, 3, 4, 5, 6, 7, 58
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Abstract
Objectives: The purpose of this study was to investigate dolutegravir (DTG) use among women and exposure to DTG during pregnancy in real world in Central and Eastern Europe and neighboring countries.
Material and methods: Centres from 20 countries included in the Euroguidelines in Central and Eastern Europe (ECEE) Network and Finland were asked to complete an on-line questionnaire.
Results: Seven centres from Czech Republic, Finland, Greece, Poland, Slovakia, and Turkey provided detailed information. DTG exposure was reported in 415 women, of which 26 were during pregnancy. Of those, 22 were on DTG at the time of conception and 4 had started DTG during pregnancy. Few women had conventional risk factors. The data on folic acid usage was unknown for eight women; 14 were using and four were not using folic acid. Four pregnancies were ongoing at the time of the study and of those with an outcome, 77.3% resulted with term, 13.6% preterm delivery, 4.5% spontaneous and 4.5% medical abortion.
Conclusions: The DTG signal report indicates the importance of safety research for drug use in pregnancy and highlights the urgent need for systematic surveillance of pregnancy outcomes and neonatal surveillance. Countries with low- or moderate HIV prevalence should be included in studies reviewing pregnancy outcomes and in any surveillance system to ensure the accuracy of drug safety revision.
Keywords: HIV infectiondolutegravirpregnancyCentral and Eastern Europe
References
- Messiaen P, Wensing AMJ, Fun A, et al. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One. 2013; 8(1): e52562.
- European AIDS Clinical Society Guidelines. Version 9.1. October 2018. Clinical Society Guidelines. Version 9.1. October 2018. http://www.eacsociety.org/files/2018_guidelines-9.1-english.pdf. (11.03.2019).
- Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection (WHO/CDS/HIV/18.51). Geneva: World Health Organization, 2018.
- Kowalska JD, Oprea C, de Witt S, et al. ECEE Network Group. Euroguidelines in Central and Eastern Europe (ECEE) conference and the Warsaw Declaration - a comprehensive meeting report. HIV Med. 2017; 18(5): 370–375.
- Zash R, Makhema J, Shapiro RL. Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception. N Engl J Med. 2018; 379(10): 979–981.
- WHO Statement on Dolutegravir. Geneva18 May 2018. WHO Statement on Dolutegravir. Geneva18 May 2018. https://www.who.int/medicines/publications/drugalerts/Statement_on_DTG_18May_2018final.pdf. (11.03.2019).
- Phillips AN, Venter F, Havlir D, et al. Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study. Lancet HIV. 2019; 6(2): e116–e127.
- Gokengin D, Oprea C, Begovac J, et al. HIV care in Central and Eastern Europe: How close are we to the target? Int J Infect Dis. 2018; 70: 121–130.
- Thorne C, Favarato G, Peters H, et al. Pregnancy and neonatal outcomes following prenatal exposure to dolutegravir. 9th IAS Conference on HIV Science; Paris, France; July 23–26. 2017: Abstract 4549.
- Vannappagari V, Albano J, Ragone L, et al. Dolutegravir use during pregnancy and birth outcomes: data from the Antiretroviral Pregnancy Registry (APR). 9th IAS Conference on HIV Science. Paris, France; July 23–26. 2017: Abstract 68.
- Vitoria M, Ford N, Clayden P, et al. When could new antiretrovirals be recommended for national treatment programmes in low-income and middle-income countries: results of a WHO Think Tank. Curr Opin HIV AIDS. 2017; 12(4): 414–422.
- Bornhede R, Soeria-Atmadja S, Westling K, et al. Dolutegravir in pregnancy-effects on HIV-positive women and their infants. Eur J Clin Microbiol Infect Dis. 2018; 37(3): 495–500.
- Zash R, Jacobson DL, Diseko M, et al. Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study. Lancet Glob Health. 2018; 6(7): e804–e810.
- New study suggests risk of birth defects in babies born to women on HIV medicine dolutegravir. European Medicines Agency Press Release 18.05.2018. New study suggests risk of birth defects in babies born to women on HIV medicine dolutegravir. European Medicines Agency Press Release 18.05.2018. https://www.ema.europa.eu/en/news/new-study-suggests-risk-birth-defects-babies-born-women-hiv-medicine-dolutegravir..
- Nakkazi E. Changes to dolutegravir policy in several African countries. Lancet. 2018; 392(10143): 199.
- Balayan T, Oprea C, Yurin O, et al. Euro-guidelines in Central and Eastern Europe Network Group. People who inject drugs remain hard-to-reach population across all HIV continuum stages in Central, Eastern and South Eastern Europe - data from Euro-guidelines in Central and Eastern Europe Network. Infect Dis (Lond). 2019; 51(4): 277–286.
- Thorne C, Semenenko I, Pilipenko T, et al. Ukraine European Collaborative Study Group. Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study. BMC Infect Dis. 2009; 9: 40.
- Rahangdale L, Cates J, Potter J, et al. HOPES (HIV OB Pregnancy Education Study) Group. Integrase inhibitors in late pregnancy and rapid HIV viral load reduction. Am J Obstet Gynecol. 2016; 214(3): 385.e1–385.e7.
- Mulligan N, Best BM, Wang J, et al. IMPAACT P1026s Protocol Team. Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV. AIDS. 2018; 32(6): 729–737.
- Grayhack C, Sheth A, Kirby O, et al. Evaluating outcomes of mother-infant pairs using dolutegravir for HIV treatment during pregnancy. AIDS. 2018; 32(14): 2017–2021.
- Mounce ML, Pontiggia L, Adams JL. A Single-Center Retrospective Cohort Analysis of Maternal and Infant Outcomes in HIV-Infected Mothers Treated with Integrase Inhibitors During Pregnancy. Infect Dis Ther. 2017; 6(4): 531–544.
- Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991; 338(8760): 131–137.
- Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992; 327(26): 1832–1835.
- Kantola-Sorsa E, Gaily E, Isoaho M, et al. Neuropsychological outcomes in children of mothers with epilepsy. J Int Neuropsychol Soc. 2007; 13(4): 642–652.
- Meador KJ, Baker GA, Finnell RH, et al. NEAD Study Group. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006; 67(3): 407–412.
- Martínez-Frías ML. Epidemiological analysis of outcomes of pregnancy in diabetic mothers: identification of the most characteristic and most frequent congenital anomalies. Am J Med Genet. 1994; 51(2): 108–113.
- Martínez-Frías ML, Bermejo E, Rodríguez-Pinilla E, et al. Epidemiological analysis of outcomes of pregnancy in gestational diabetic mothers. Am J Med Genet. 1998; 78(2): 140–145.
- McMahon DM, Liu J, Zhang H, et al. Maternal obesity, folate intake, and neural tube defects in offspring. Birth Defects Res A Clin Mol Teratol. 2013; 97(2): 115–122.
- Kowalska JD, Aebi-Popp K, Loutfy M, et al. Women Against Viruses in Europe (WAVE) Working Group. Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group. HIV Med. 2018; 19(2): 167–173.
- Weissmann D, De Le, Gute P, et al. Use of integrase inhibitors in HIV-positive pregnant women: data from the Frankfurt HIV cohort. HIV Drug Therapy. ; 2018: P002.
- Sibiude J, Le Ch, Mandelbrot L, et al. No increase in birth defects in infants exposed to integrase inhibitors at conception. Conference on Retroviruses and Opportunistic Infections. March 4–7 2019, Seattle, USA. : Abstract no. 744.
- Hill A, van de, Pozniak A, et al. et al.. Reports of neural tube defects for 8 ARTs, , WHO, EMA, and UK safety databases. Conference on Retroviruses and Opportunistic Infections. March 4–7 2019, Seattle, USA. : Abstract no. 746.
- Albano JD, Vannappagari V, Scheuerle A, et al. InSTIexposure and neural tube defects: data from antiretroviral pregnancy registry. Conference on Retroviruses and Opportunistic Infections. March 4–7 2019, Seattle, USA. : Abstract no. 747.
- Dolutegravir for HIV: a lesson in pregnancy safety research. Lancet. 2018; 391(10137): 2296.
- Schomaker M, Davies MA, Cornell M, et al. Assessing the risk of dolutegravir for women of childbearing potential. Lancet Glob Health. 2018; 6(9): e958–e959.
