In utero exposure to antiretroviral drugs and pregnancy outcomes: Analysis of the French ANRS pharmacovigilance database.
ANRS
HIV
adverse pregnancy outcomes
antiretroviral drugs
pharmacovigilance
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
13
08
2021
received:
09
04
2021
accepted:
25
08
2021
pubmed:
11
9
2021
medline:
27
4
2022
entrez:
10
9
2021
Statut:
ppublish
Résumé
In 2018, 1.07 million pregnant women received antiretroviral drugs, raising whether this affects pregnancy outcomes. We assessed the adverse pregnancy outcomes associated with prenatal antiretroviral drug exposure, notified to the French ANRS pharmacovigilance system. An exhaustive case report series has been performed using the ANRS pharmacovigilance database. All ANRS-sponsored HIV clinical research studies using antiretroviral drugs either in pregnant women or women of childbearing age were eligible from 2004 to 2019. We analysed the following pregnancy outcomes: abortion, ectopic pregnancy, stillbirth, prematurity (<37 weeks of gestational age), low birth weight (<2500 g) and congenital abnormalities. A logistic regression was performed to assess the odds ratio (OR) for each outcome separately (if occurrence >50) compared to the outcome observed when exposed to non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based regimen as the reference. Among the 34 studies selected, 918 deliveries occurred, of whom 88% had pregnancy outcomes documented. Pregnant women were mainly exposed to PI (n = 387, 48.6%), NNRTI (n = 331, 41.5%) and INI-based combinations (n = 40, 5.0%, 18 on dolutegravir). Compared to NNRTI-based combinations, there was no significant association observed with exposure to other antiretroviral combination for spontaneous abortion, prematurity or low birth weight, except an increased risk of low birth weight in new-born exposed to exclusive nucleoside-reverse-transcriptase-inhibitor (NRTI) combinations (n = 4; OR 7.50 [1.49-37.83]). Our study, mainly based on protease inhibitor (PI) and NNRTI-based regimens, is overall reassuring on the risk of adverse pregnancy outcomes, except for NRTI which should be interpreted cautiously (small number, indication bias). In this study, the number of integrase inhibitor (INI)-based combinations was too low to draw any conclusions.
Substances chimiques
Anti-HIV Agents
0
HIV Integrase Inhibitors
0
Reverse Transcriptase Inhibitors
0
DNA-Directed RNA Polymerases
EC 2.7.7.6
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
942-964Informations de copyright
© 2021 British Pharmacological Society.
Références
UNAIDS. 2020 Global AIDS Update-Seizing the moment-Tackling entrenched inequalities to end epidemics. https://www.unaids.org/en/resources/documents/2020/global-aids-report. Published July 6, 2020. Accessed December 14, 2020.
WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. http://www.who.int/hiv/pub/arv/arv-2016/en/. Published June 2016. Accessed December 14, 2020.
Wedi COO, Kirtley S, Hopewell S, Corrigan R, Kennedy SH, Hemelaar J. Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis. Lancet HIV. 2016;3(1):e33-e48. https://doi.org/10.1016/S2352-3018(15)00207-6
WHO. Lignes directrices unifiées relatives à l'utilisation de médicaments antirétroviraux pour le traitement et la prévention de l'infection à VIH. http://www.who.int/hiv/pub/arv/policy-brief-arv-2015/fr/. Published November 2015. Accessed March 23, 2018.
Schulte J, Dominguez K, Sukalac T, Bohannon B, Fowler MG, for the Pediatric Spectrum of HIV Disease Consortium. Declines in low birth weight and preterm birth among infants who were born to HIV-infected women during an era of increased use of maternal antiretroviral drugs: pediatric spectrum of HIV disease, 1989-2004. Pediatrics. 2007;119(4):e900-e906. https://doi.org/10.1542/peds.2006-1123
Simon A, Warszawski J, Kariyawasam D, et al. Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among uninfected infants of HIV-infected mothers. JAMA. 2011;306(1):70-78. https://doi.org/10.1001/jama.2011.915
Sibiude J, Warszawski J, Tubiana R, et al. Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost? Clin Infect Dis. 2012;54(9):1348-1360. https://doi.org/10.1093/cid/cis198
Ørbaek M, Thorsteinsson K, Moseholm Larsen E, et al. Risk factors during pregnancy and birth-related complications in HIV-positive versus HIV-negative women in Denmark, 2002-2014. HIV Med. 2020;21(2):84-95. https://doi.org/10.1111/hiv.12798
Williams PL, Yildirim C, Chadwick EG, et al. Association of maternal antiretroviral use with microencephaly in children who are HIV-exposed but uninfected (SMARTT): a prospective cohort study. Lancet HIV. 2020;7(1):e49-e58. https://doi.org/10.1016/S2352-3018(19)30340-6
Tookey PA, Thorne C, van Wyk J, Norton M. Maternal and foetal outcomes among 4118 women with HIV infection treated with lopinavir/ritonavir during pregnancy: analysis of population-based surveillance data from the national study of HIV in pregnancy and childhood in the United Kingdom and Ireland. BMC Infect Dis. 2016;16(1):65-77. https://doi.org/10.1186/s12879-016-1400-y
Watts DH, Williams PL, Kacanek D, et al. Combination antiretroviral use and preterm birth. J Infect Dis. 2013;207(4):612-621. https://doi.org/10.1093/infdis/jis728
Mofenson LM. In-utero ART exposure and the need for pharmacovigilance. Lancet Glob Health. 2018;6(7):e716-e717.
WHO. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV. https://www.who.int/publications/i/item/WHO-CDS-HIV-18.51. Published July 2018. Accessed September 15, 2021.
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 - ScienceDirect. Lancet Glob Health. 2018;6(7):e804-e810.
Zash R, Holmes L, Diseko M, et al. Neural-tube defects and antiretroviral treatment regimens in Botswana. N Engl J Med. 2019;381(9):827-840. https://doi.org/10.1056/NEJMoa1905230
WHO. Update of recommendations on first- and second-line antiretroviral regimens. https://apps.who.int/iris/bitstream/handle/10665/325892/WHO-CDS-HIV-19.15-eng.pdf?ua=1. Published online July 1, 2019. Accessed September 15, 2021.
Farlex Partner Medical Dictionary ©. Induced abortion. https://medical-dictionary.thefreedictionary.com/induced+abortion. Published 2012. Accessed April 3, 2018.
Ameli. Fausse couche. https://www.ameli.fr/assure/sante/urgence/pathologies/fausse-couche. Published April 7, 2020. Accessed February 19, 2018.
Collège National des Gynécologues et Obstétriciens Français. Grossesse extra-utérine. http://www.cngof.net/E-book/GO-2016/09-ch02-09-16-9782294715518-GEU.html. Grossesse extra-utérine. Published online 2016. Accessed June 17, 2019.
CDC. What is Stillbirth?. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/stillbirth/facts.html. Published November 16, 2020. Accessed July 9, 2021.
WHO. Stillbirths. WHO. http://www.who.int/maternal_child_adolescent/epidemiology/stillbirth/en/. Published 2015. Accessed March 22, 2018.
WHO. Preterm birth. WHO. https://www.who.int/news-room/fact-sheets/detail/preterm-birth. Published 2018. Accessed January 9, 2019.
WHO. Newborns with low birth weight. WHO. http://webcache.googleusercontent.com/search?q=cache:-JeHP_u3DZAJ:www.who.int/whosis/whostat2006NewbornsLowBirthWeight.pdf+&cd=6&hl=fr&ct=clnk&gl=fr&client=firefox-b. Published 2006. Accessed March 22, 2018.
WHO. Congenital anomalies. https://www.who.int/news-room/fact-sheets/detail/congenital-anomalies. Published 2016. Accessed January 9, 2019.
EUROCAT. EUROCAT Guide 1.4: Instruction for the registration of congenital anomalies. EUROCAT Central Registry, University of Ulster. https://eu-rd-platform.jrc.ec.europa.eu/sites/default/files/Full_Guide_1_4_version_28_DEC2018.pdf. Published 2013. Accessed September 13, 2019.
World Bank Country and Lending Groups - World Bank Data Help Desk. https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups. Accessed July 9, 2021.
Katlama C, Valantin MA, Algarte-Genin M, et al. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010;24(15):2365-2374. https://doi.org/10.1097/QAD.0b013e32833dec20
Parienti J-J, Barrail-Tran A, Duval X, et al. Adherence profiles and therapeutic responses of treatment-naive HIV-infected patients starting boosted atazanavir-based therapy in the ANRS 134-COPHAR 3 trial. Antimicrob Agents Chemother. 2013;57(5):2265-2271. https://doi.org/10.1128/AAC.02605-12
Garay OU, Nishimwe ML, Bousmah M-A-Q, et al. Cost-effectiveness analysis of lopinavir/ritonavir monotherapy versus standard combination antiretroviral therapy in HIV-1 infected patients with viral suppression in France (ANRS 140 DREAM). Pharmacoecon Open. 2019;3(4):505-515. https://doi.org/10.1007/s41669-019-0130-7
Tubiana R, Mandelbrot L, Le Chenadec J, et al. Lopinavir/ritonavir monotherapy as a nucleoside analogue-sparing strategy to prevent HIV-1 mother-to-child transmission: the ANRS 135 PRIMEVA phase 2/3 randomized trial. Clin Infect Dis. 2013;57(6):891-902. https://doi.org/10.1093/cid/cit390
Raffi F, Babiker AG, Richert L, et al. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial. Lancet. 2014;384(9958):1942-1951. https://doi.org/10.1016/S0140-6736(14)61170-3
Chéret A, Nembot G, Mélard A, et al. Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial. Lancet Infect Dis. 2015;15(4):387-396. https://doi.org/10.1016/S1473-3099(15)70021-6
Colin de Verdiere N, Durier C, Samri A, et al. Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients. AIDS. 2018;32(16):2291-2299. https://doi.org/10.1097/QAD.0000000000001963
Poizot-Martin I, Bellissant E, Garraffo R, et al. Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study. HIV Clin Trials. 2016;17(2):63-71. https://doi.org/10.1080/15284336.2015.1135553
Pourcher V, Desnoyer A, Assoumou L, et al. Phase II trial of lenalidomide in HIV-infected patients with previously treated Kaposi's sarcoma: results of the ANRS 154 lenakap trial. AIDS Res Hum Retroviruses. 2017;33(1):1-10. https://doi.org/10.1089/AID.2016.0069
Lévy Y, Lelièvre J-D, Assoumou L, et al. Addition of maraviroc versus placebo to standard antiretroviral therapy for initial treatment of advanced HIV infection: a randomized trial. Ann Intern Med. 2020;(5):297-305. https://doi.org/10.7326/M19-2133
de Truchis P, Assoumou L, Landman R, et al. Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial. J Antimicrob Chemother. 2018;73(3):738-747. https://doi.org/10.1093/jac/dkx434
Lê MP, Chaix M-L, Chevret S, et al. Pharmacokinetic modelling of darunavir/ritonavir dose reduction (800/100 to 400/100 mg once daily) in a darunavir/ritonavir-containing regimen in virologically suppressed HIV-infected patients: ANRS 165 DARULIGHT sub-study. J Antimicrob Chemother. 2018;73(8):2120-2128. https://doi.org/10.1093/jac/dky193
Laurent C, Kouanfack C, Laborde-Balen G, et al. Monitoring of HIV viral loads, CD4 cell counts, and clinical assessments versus clinical monitoring alone for antiretroviral therapy in rural district hospitals in Cameroon (Stratall ANRS 12110/ESTHER): a randomised non-inferiority trial. Lancet Infect Dis. 2011;11(11):825-833. https://doi.org/10.1016/S1473-3099(11)70168-2
Hirt D, Urien S, Ekouévi DK, et al. Population pharmacokinetics of tenofovir in HIV-1-infected pregnant women and their neonates (ANRS 12109). Clin Pharmacol Ther. 2009;85(2):182-189. https://doi.org/10.1038/clpt.2008.201
Blanc F-X, Havlir DV, Onyebujoh PC, Thim S, Goldfeld AE, Delfraissy J-F. Treatment strategies for HIV-infected patients with tuberculosis: ongoing and planned clinical trials. J Infect Dis. 2007;196(Suppl 1):S46-S51. https://doi.org/10.1086/518658
Bonnet M, Bhatt N, Baudin E, et al. Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial. Lancet Infect Dis. 2013;13(4):303-312. https://doi.org/10.1016/S1473-3099(13)70007-0
TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373(9):808-822. https://doi.org/10.1056/NEJMoa1507198
Boyer S, Nishimwe ML, Sagaon-Teyssier L, et al. Cost-effectiveness of three alternative boosted protease inhibitor-based second-line regimens in HIV-infected patients in West and Central Africa. Pharmacoecon Open. 2020;4(1):45-60. https://doi.org/10.1007/s41669-019-0157-9
Grinsztejn B, De Castro N, Arnold V, et al. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial. Lancet Infect Dis. 2014;14(6):459-467. https://doi.org/10.1016/S1473-3099(14)70711-X
Kouanfack C, Unal G, Schaeffer L, et al. Comparative immunovirological and clinical responses to antiretroviral therapy between HIV-1 Group O and HIV-1 Group M infected patients. Clin Infect Dis. 2020;70(7):1471-1477. https://doi.org/10.1093/cid/ciz371
Iwuji CC, Orne-Gliemann J, Tanser F, et al. Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial. Trials. 2013;14(1):230-245. https://doi.org/10.1186/1745-6215-14-230
Ciaffi L, Koulla-Shiro S, Sawadogo AB, et al. Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial. Lancet HIV. 2017;4(9):e384-e392. https://doi.org/10.1016/S2352-3018(17)30069-3
NAMSAL ANRS 12313 Study Group, Kouanfack C, Mpoudi-Etame M, et al. Dolutegravir-based or low-dose efavirenz-based regimen for the treatment of HIV-1. N Engl J Med. 2019;381(9):816-826. https://doi.org/10.1056/NEJMoa1904340
WHO. Child health. WHO|Regional Office for Africa. https://www.afro.who.int/health-topics/child-health. Published 2015. Accessed August 13, 2021.
WHO. Probability of dying before age 5 per 1000 live births. https://gateway.euro.who.int/en/indicators/hfa_61-1070-probability-of-dying-before-age-5-per-1000-live-births/. Accessed August 13, 2021.
Ekouevi DK, Coffie PA, Ouattara E, et al. Pregnancy outcomes in women exposed to efavirenz and nevirapine: an appraisal of the IeDEA West Africa and ANRS Databases, Abidjan, Côte d'Ivoire. J Acquir Immune Defic Syndr. 2011;56(2):183-187. https://doi.org/10.1097/QAI.0b013e3181ff04e6
Stringer JSA, McConnell MS, Kiarie J, et al. Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study. PLoS Med. 2010;7(2):e1000233. https://doi.org/10.1371/journal.pmed.1000233
Rempis EM, Schnack A, Decker S, et al. Option B+ for prevention of vertical HIV transmission has no influence on adverse birth outcomes in a cross-sectional cohort in Western Uganda. BMC Pregnancy Childbirth. 2017;17(1):82-94. https://doi.org/10.1186/s12884-017-1263-2
Snijdewind IJM, Smit C, Godfried MH, et al. Preconception use of cART by HIV-positive pregnant women increases the risk of infants being born small for gestational age. PLoS ONE. 2018;13(1):e0191389. https://doi.org/10.1371/journal.pone.0191389
Phiri K, Fischer MA, Mogun H, et al. Trends in antiretroviral drug use during pregnancy among HIV-infected women on Medicaid: 2000-2007. AIDS Patient Care STDS. 2014;28(2):56-65. https://doi.org/10.1089/apc.2013.0165
Bisio F, Nicco E, Calzi A, et al. Pregnancy outcomes following exposure to efavirenz-based antiretroviral therapy in the Republic of Congo. New Microbiol. 2015;38(2):185-192.
Roberts O, Khoo S, Owen A, Siccardi M. Interaction of rifampin and darunavir-ritonavir or darunavir-cobicistat in vitro. Antimicrob Agents Chemother. 2017;61(5):e01776-16. https://doi.org/10.1128/AAC.01776-16
van der Merwe K, Hoffman R, Black V, Chersich M, Coovadia A, Rees H. Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study. J Int AIDS Soc. 2011;14(1):42-53. https://doi.org/10.1186/1758-2652-14-42
Perry MEO, Taylor GP, Sabin CA, et al. Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological efficacies and preterm delivery rates. HIV Med. 2016;17(1):28-35. https://doi.org/10.1111/hiv.12277
Covington DL, Conner SD, Doi PA, Swinson J, Daniels EM. Risk of birth defects associated with nelfinavir exposure during pregnancy. Obstet Gynecol. 2004;103(6):1181-1189. https://doi.org/10.1097/01.AOG.0000127440.68730.23
Mofenson LM, Pozniak AL, Wambui J, et al. Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects. J Int AIDS Soc. 2019;22(7):e25352. https://doi.org/10.1002/jia2.25352
van De Ven NS, Pozniak AL, Levi JA, et al. Analysis of pharmacovigilance databases for dolutegravir safety in pregnancy. Clin Infect Dis. 2019;70(12):2599-2606. https://doi.org/10.1093/cid/ciz684
Abrams EJ, Mofenson LM, Pozniak A, et al. Enhanced and timely investigation of ARVs for use in pregnant women. J Acquir Immune Defic Syndr. 2021;86(5):607-615. https://doi.org/10.1097/QAI.0000000000002597
Wingate MS, Alexander GR, Buekens P, Vahratian A. Comparison of gestational age classifications: date of last menstrual period vs. clinical estimate. Ann Epidemiol. 2007;17(6):425-430. https://doi.org/10.1016/j.annepidem.2007.01.035
Tsamantioti ES, Hashmi MF. Teratogenic medications. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2021. http://www.ncbi.nlm.nih.gov/books/NBK553086/. Accessed July 21, 2021.
Oztarhan K, Gedikbasi A, Yildirim D, et al. Prevalence and distribution of congenital abnormalities in Turkey: differences between the prenatal and postnatal periods. Congenit Anom. 2010;50(4):221-225. https://doi.org/10.1111/j.1741-4520.2010.00288.x
Birch M-R, Grayson N, Sullivan EA. Recommendations for Development of a New Australian Birth Anomalies System: A Review of the National Congenital Malformations and Birth Defects Data Collection. Australian Institute of Health and Welfare National Perinatal Statistics Unit; 2004.
WHO. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV guidelines. http://apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf?ua=1. Published September 2015. Accessed June 10, 2018.