UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Safety and dosing of antiretroviral medications in pregnancy

Author
Elaine J Abrams, MD
Section Editor
Lynne M Mofenson, MD
Deputy Editor
Allyson Bloom, MD

INTRODUCTION

Decisions regarding antiretroviral therapy in the pregnant female are complex and, beyond the typical considerations of virologic potency, side effects, and formulation, need to also take into consideration other factors, such as possible changes in pharmacokinetics due to physiologic changes, potential toxicities that may be magnified during pregnancy, and potential toxicity to the fetus and/or newborn.

This topic will address the clinical data on the safety and pharmacology of the more commonly used antiretroviral medications during pregnancy. Antiretrovirals that are not commonly used or used only in limited situations are not discussed in this topic. Guidelines for antiretroviral therapy of pregnant HIV-infected women in the United States are developed by the Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission; these guidelines include detailed information on the safety and pharmacokinetics of antiretroviral drugs in pregnancy [1]. Guidelines for antiretroviral therapy of pregnant women residing in resource-limited settings, where antiretroviral drug access may be more limited and preferred drug choices may differ, are developed by the World Health Organization (WHO) and may differ from recommendations in the United States; WHO guideline updates can be found on its website.

Antiretroviral selection and other management issues for the HIV-infected pregnant woman are discussed in detail elsewhere. (See "Antiretroviral and intrapartum management of pregnant HIV-infected women and their infants in resource-rich settings" and "Prenatal evaluation of the HIV-infected woman in resource-rich settings" and "Prevention of mother-to-child HIV transmission in resource-limited settings".)

GENERAL PRINCIPLES

Antiretroviral therapy (ART) is recommended for all HIV-infected individuals, including pregnant women, regardless of immune, clinical, or viral status [2]. ART reduces HIV-related morbidity and mortality, even in individuals with high CD4 cell counts [3,4]. An additional goal of ART in pregnant women is to decrease the risk of perinatal transmission of HIV infection.

In pregnant women, antiretroviral regimen selection should take into account the resistance profile of the virus, the safety and efficacy of the drugs in the mother and fetus, the convenience and adherence potential of the regimen, the potential for drug interactions with other medications, and pharmacokinetic data in pregnancy. In resource-rich settings, certain antiretroviral agents that are recommended in the general HIV-infected population are not preferred agents for pregnant women because of limited experience during pregnancy. On the other hand, certain agents that are not recommended in the general population are preferred for pregnant women because of extensive clinical experience during pregnancy. In general, treatment-naïve women should be treated with a regimen made up of preferred agents, if the resistance profile of the virus allows. Treatment-experienced women on a suppressive antiretroviral regimen can continue it even if the agents are not specifically preferred during pregnancy. Preferred antiretroviral agents in pregnancy and regimen selection for pregnant women are discussed in detail elsewhere. (See "Antiretroviral and intrapartum management of pregnant HIV-infected women and their infants in resource-rich settings" and "Prevention of mother-to-child HIV transmission in resource-limited settings".)

                                                      

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Fri Nov 18 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. http://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/0/ (Accessed on October 26, 2016).
  2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf (Accessed on April 08, 2015).
  3. 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; 373:808.
  4. INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med 2015; 373:795.
  5. Chen JY, Ribaudo HJ, Souda S, et al. Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana. J Infect Dis 2012; 206:1695.
  6. Ndirangu J, Newell ML, Bland RM, Thorne C. Maternal HIV infection associated with small-for-gestational age infants but not preterm births: evidence from rural South Africa. Hum Reprod 2012; 27:1846.
  7. Schulte J, Dominguez K, Sukalac T, et al. 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:e900.
  8. Briand N, Mandelbrot L, Le Chenadec J, et al. No relation between in-utero exposure to HAART and intrauterine growth retardation. AIDS 2009; 23:1235.
  9. Floridia M, Ravizza M, Bucceri A, et al. Factors influencing gestational age-adjusted birthweight in a national series of 600 newborns from mothers with HIV. HIV Clin Trials 2008; 9:287.
  10. Szyld EG, Warley EM, Freimanis L, et al. Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth. AIDS 2006; 20:2345.
  11. Cotter AM, Garcia AG, Duthely ML, et al. Is antiretroviral therapy during pregnancy associated with an increased risk of preterm delivery, low birth weight, or stillbirth? J Infect Dis 2006; 193:1195.
  12. Tuomala RE, Shapiro DE, Mofenson LM, et al. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. N Engl J Med 2002; 346:1863.
  13. Ekouevi DK, Coffie PA, Becquet R, et al. Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Côte d'Ivoire. AIDS 2008; 22:1815.
  14. Njom Nlend AE, Nga Motazé A, Moyo Tetang S, et al. Preterm Birth and Low Birth Weight after In Utero Exposure to Antiretrovirals Initiated during Pregnancy in Yaoundé, Cameroon. PLoS One 2016; 11:e0150565.
  15. Kourtis AP, Schmid CH, Jamieson DJ, Lau J. Use of antiretroviral therapy in pregnant HIV-infected women and the risk of premature delivery: a meta-analysis. AIDS 2007; 21:607.
  16. Townsend C, Schulte J, Thorne C, et al. Antiretroviral therapy and preterm delivery-a pooled analysis of data from the United States and Europe. BJOG 2010; 117:1399.
  17. Powis KM, Kitch D, Ogwu A, et al. Increased risk of preterm delivery among HIV-infected women randomized to protease versus nucleoside reverse transcriptase inhibitor-based HAART during pregnancy. J Infect Dis 2011; 204:506.
  18. Rudin C, Spaenhauer A, Keiser O, et al. Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data. HIV Med 2011; 12:228.
  19. Lopez M, Figueras F, Hernandez S, et al. Association of HIV infection with spontaneous and iatrogenic preterm delivery: effect of HAART. AIDS 2012; 26:37.
  20. 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; 54:1348.
  21. Patel K, Shapiro DE, Brogly SB, et al. Prenatal protease inhibitor use and risk of preterm birth among HIV-infected women initiating antiretroviral drugs during pregnancy. J Infect Dis 2010; 201:1035.
  22. Chou R, Cantor AG, Zakher B, Bougatsos C. Screening for HIV in pregnant women: systematic review to update the 2005 U.S. Preventive Services Task Force recommendation. Ann Intern Med 2012; 157:719.
  23. Li N, Sando MM, Spiegelman D, et al. Antiretroviral Therapy in Relation to Birth Outcomes among HIV-infected Women: A Cohort Study. J Infect Dis 2016; 213:1057.
  24. Fowler MG, Qin M, Fiscus SA, et al. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention. N Engl J Med 2016; 375:1726.
  25. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989 through 31 January 2016. Wilmington, NC: Registry Coordinating Center; 2016. www.APRegistry.com (Accessed on November 06, 2016).
  26. Gibb DM, Kizito H, Russell EC, et al. Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial. PLoS Med 2012; 9:e1001217.
  27. Williams PL, Crain MJ, Yildirim C, et al. Congenital anomalies and in utero antiretroviral exposure in human immunodeficiency virus-exposed uninfected infants. JAMA Pediatr 2015; 169:48.
  28. Lipshultz SE, Williams PL, Zeldow B, et al. Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers. AIDS 2015; 29:91.
  29. Sibiude J, Le Chenadec J, Bonnet D, et al. In utero exposure to zidovudine and heart anomalies in the ANRS French perinatal cohort and the nested PRIMEVA randomized trial. Clin Infect Dis 2015; 61:270.
  30. Currier JS. Sex differences in antiretroviral therapy toxicity: lactic acidosis, stavudine, and women. Clin Infect Dis 2007; 45:261.
  31. Bolhaar MG, Karstaedt AS. A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa. Clin Infect Dis 2007; 45:254.
  32. Bristol-Myers Squibb Company. Heatlhcare Provider Important Drug Warning Letter. January 5, 2001.
  33. Sarner L, Fakoya A. Acute onset lactic acidosis and pancreatitis in the third trimester of pregnancy in HIV-1 positive women taking antiretroviral medication. Sex Transm Infect 2002; 78:58.
  34. Mandelbrot L, Kermarrec N, Marcollet A, et al. Case report: nucleoside analogue-induced lactic acidosis in the third trimester of pregnancy. AIDS 2003; 17:272.
  35. Pacheco SE, McIntosh K, Lu M, et al. Effect of perinatal antiretroviral drug exposure on hematologic values in HIV-uninfected children: An analysis of the women and infants transmission study. J Infect Dis 2006; 194:1089.
  36. European Collaborative Study. Levels and patterns of neutrophil cell counts over the first 8 years of life in children of HIV-1-infected mothers. AIDS 2004; 18:2009.
  37. Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, et al. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 2001; 285:2083.
  38. Blanche S, Tardieu M, Rustin P, et al. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet 1999; 354:1084.
  39. Barret B, Tardieu M, Rustin P, et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS 2003; 17:1769.
  40. Benhammou V, Tardieu M, Warszawski J, et al. Clinical mitochondrial dysfunction in uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues. Environ Mol Mutagen 2007; 48:173.
  41. Sperling RS, Shapiro DE, McSherry GD, et al. Safety of the maternal-infant zidovudine regimen utilized in the Pediatric AIDS Clinical Trial Group 076 Study. AIDS 1998; 12:1805.
  42. Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts. J Acquir Immune Defic Syndr 2000; 25:261.
  43. Lipshultz SE, Easley KA, Orav EJ, et al. Absence of cardiac toxicity of zidovudine in infants. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study Group. N Engl J Med 2000; 343:759.
  44. European Collaborative Study. Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women. J Acquir Immune Defic Syndr 2003; 32:380.
  45. Alimenti A, Forbes JC, Oberlander TF, et al. A prospective controlled study of neurodevelopment in HIV-uninfected children exposed to combination antiretroviral drugs in pregnancy. Pediatrics 2006; 118:e1139.
  46. Brogly SB, Ylitalo N, Mofenson LM, et al. In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV-uninfected children. AIDS 2007; 21:929.
  47. Hanson IC, Antonelli TA, Sperling RS, et al. Lack of tumors in infants with perinatal HIV-1 exposure and fetal/neonatal exposure to zidovudine. J Acquir Immune Defic Syndr Hum Retrovirol 1999; 20:463.
  48. Brogly S, Williams P, Seage GR 3rd, Van Dyke R. In utero nucleoside reverse transcriptase inhibitor exposure and cancer in HIV-uninfected children: an update from the pediatric AIDS clinical trials group 219 and 219C cohorts. J Acquir Immune Defic Syndr 2006; 41:535.
  49. Hankin C, Lyall H, Peckham C, Tookey P. Monitoring death and cancer in children born to HIV-infected women in England and Wales: use of HIV surveillance and national routine data. AIDS 2007; 21:867.
  50. Benhammou V, Warszawski J, Bellec S, et al. Incidence of cancer in children perinatally exposed to nucleoside reverse transcriptase inhibitors. AIDS 2008; 22:2165.
  51. Ivy W 3rd, Nesheim SR, Paul SM, et al. Cancer Among Children With Perinatal Exposure to HIV and Antiretroviral Medications--New Jersey, 1995-2010. J Acquir Immune Defic Syndr 2015; 70:62.
  52. Vannappagari V, Koram N, Albano J, et al. Abacavir and lamivudine exposures during pregnancy and non-defect adverse pregnancy outcomes: data from the antiretroviral pregnancy registry. J Acquir Immune Defic Syndr 2015; 68:359.
  53. Best BM, Mirochnick M, Capparelli EV, et al. Impact of pregnancy on abacavir pharmacokinetics. AIDS 2006; 20:553.
  54. Schalkwijk S, Colbers A, Konopnicki D, et al. The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women. AIDS 2016; 30:1239.
  55. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, second edition. June 2016. http://www.who.int/hiv/pub/arv/arv-2016/en/ (Accessed on June 15, 2016).
  56. Colbers AP, Hawkins DA, Gingelmaier A, et al. The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women. AIDS 2013; 27:739.
  57. Benaboud S, Tréluyer JM, Urien S, et al. Pregnancy-related effects on lamivudine pharmacokinetics in a population study with 228 women. Antimicrob Agents Chemother 2012; 56:776.
  58. Van Rompay KK, Durand-Gasselin L, Brignolo LL, et al. Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects. Antimicrob Agents Chemother 2008; 52:3144.
  59. Mofenson LM, Baggaley RC, Mameletzis I. Tenofovir Disoproxil Fumarate Safety for Women and their Infants during Pregnancy and Breastfeeding: Systematic Review. AIDS 2016.
  60. M le Roux S, Jao J, Brittain K, et al. Tenofovir exposure in utero and linear growth in HIV-exposed, uninfected infants. AIDS 2017; 31:97.
  61. Zash R, Souda S, Chen JY, et al. Reassuring Birth Outcomes With Tenofovir/Emtricitabine/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana. J Acquir Immune Defic Syndr 2016; 71:428.
  62. Siberry GK, Williams PL, Mendez H, et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS 2012; 26:1151.
  63. Liotta G, Floridia M, Andreotti M, et al. Growth indices in breastfed infants pre and postnatally exposed to tenofovir compared with tenofovir-unexposed infants. AIDS 2016; 30:525.
  64. L Stranix-Chibanda et al. Impact of maternal antiretroviral therapy (ART) versus infant nevirapine prophylaxis on somatic growth of breastfeeding infants in the PROMISE trial. Presented at the 8th International Workshop on HIV Pediatrics, Durban, South Africa, July 2016.
  65. Siberry GK, Jacobson DL, Kalkwarf HJ, et al. Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy. Clin Infect Dis 2015; 61:996.
  66. Tarantal AF, Castillo A, Ekert JE, et al. Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta). J Acquir Immune Defic Syndr 2002; 29:207.
  67. Siberry GK, Tierney C, Stranix-Chibanda L, et al. P1084s: impact of maternal tenofovir disoproxil fumarate (TDF) use on HIV-exposed newborn bone mineral content. Conference on Retroviruses and Opportunistic Infections. February 2016, Boston, MA. Abs. 36.
  68. Stranix-Chibanda L, et al. Impact of tenofovir-containing triple antiretroviral therapy (ART) on bone mineral density in HIV-infected breastfeeding women in sub-Saharan Africa. Presented at the 8th International Workshop on HIV Pediatrics, Durban, South Africa, July 2016.
  69. Benaboud S, Hirt D, Launay O, et al. Pregnancy-related effects on tenofovir pharmacokinetics: a population study with 186 women. Antimicrob Agents Chemother 2012; 56:857.
  70. Best BM, Burchett S, Li H, et al. Pharmacokinetics of tenofovir during pregnancy and postpartum. HIV Med 2015; 16:502.
  71. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994; 331:1173.
  72. White A, Eldridge R, Andrews E. Birth outcomes following zidovudine exposure in pregnant women: the Antiretroviral Pregnancy Registry. Acta Paediatr Suppl 1997; 421:86.
  73. Tariq S, Townsend CL, Cortina-Borja M, et al. Use of zidovudine-sparing HAART in pregnant HIV-infected women in Europe: 2000-2009. J Acquir Immune Defic Syndr 2011; 57:326.
  74. Newschaffer CJ, Cocroft J, Anderson CE, et al. Prenatal zidovudine use and congenital anomalies in a medicaid population. J Acquir Immune Defic Syndr 2000; 24:249.
  75. Sibiude J, Mandelbrot L, Blanche S, et al. Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the French perinatal cohort study (ANRS CO1/CO11). PLoS Med 2014; 11:e1001635.
  76. Vannappagari V, Albano JD, Koram N, et al. Prenatal exposure to zidovudine and risk for ventricular septal defects and congenital heart defects: data from the Antiretroviral Pregnancy Registry. Eur J Obstet Gynecol Reprod Biol 2016; 197:6.
  77. Culnane M, Fowler M, Lee SS, et al. Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams. JAMA 1999; 281:151.
  78. Vannappagari V, Koram N, Albano J, et al. Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry. BJOG 2016; 123:910.
  79. O'Sullivan MJ, Boyer PJ, Scott GB, et al. The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants: phase I acquired immunodeficiency syndrome clinical trials group study (protocol 082). Zidovudine Collaborative Working Group. Am J Obstet Gynecol 1993; 168:1510.
  80. Ford N, Mofenson L, Shubber Z, et al. Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis. AIDS 2014; 28 Suppl 2:S123.
  81. Mofenson LM, Watts DH. Safety of pediatric HIV elimination: the growing population of HIV- and antiretroviral-exposed but uninfected infants. PLoS Med 2014; 11:e1001636.
  82. Brogly SB, Abzug MJ, Watts DH, et al. Birth defects among children born to human immunodeficiency virus-infected women: pediatric AIDS clinical trials protocols 219 and 219C. Pediatr Infect Dis J 2010; 29:721.
  83. Knapp KM, Brogly SB, Muenz DG, et al. Prevalence of congenital anomalies in infants with in utero exposure to antiretrovirals. Pediatr Infect Dis J 2012; 31:164.
  84. Shanske AL. Bilateral oblique facial clefts and extremity anomaly in an infant after intrauterine efavirenz exposure and review of its teratogenic risk. AIDS 2012; 26:1775.
  85. Nightingale SL. From the Food and Drug Administration. JAMA 1998; 280:1472.
  86. Watts DH. Teratogenicity risk of antiretroviral therapy in pregnancy. Curr HIV/AIDS Rep 2007; 4:135.
  87. de Ruiter A, Taylor GP, Clayden P, et al. British HIV Association guidelines for the management of HIV infection in pregnant women 2012 (2014 interim review). HIV Med 2014; 15 Suppl 4:1.
  88. Hoffmann CJ, Charalambous S, Thio CL, et al. Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B. AIDS 2007; 21:1301.
  89. Sonderup MW, Maughan D, Gogela N, et al. Identification of a novel and severe pattern of efavirenz drug-induced liver injury in South Africa. AIDS 2016; 30:1483.
  90. Cressey TR, Stek A, Capparelli E, et al. Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum. J Acquir Immune Defic Syndr 2012; 59:245.
  91. Colbers A, Gingelmaier A, van der Ende M, et al. Pharmacokinetics, safety and transplacental passage of rilpivirine in pregnancy: two cases. AIDS 2014; 28:288.
  92. Knudtson E, Para M, Boswell H, Fan-Havard P. Drug rash with eosinophilia and systemic symptoms syndrome and renal toxicity with a nevirapine-containing regimen in a pregnant patient with human immunodeficiency virus. Obstet Gynecol 2003; 101:1094.
  93. Lyons F, Hopkins S, McGeary A, et al. Nevirapine tolerability in HIV infected women in pregnancy - A word of caution. 2nd IAS Conference on HIV Pathogenesis and Treatment. Paris, France. July 13-16, 2003 (late breaker).
  94. Hitti J, Frenkel LM, Stek AM, et al. Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022. J Acquir Immune Defic Syndr 2004; 36:772.
  95. Timmermans S, Tempelman C, Godfried MH, et al. Nelfinavir and nevirapine side effects during pregnancy. AIDS 2005; 19:795.
  96. Langlet P, Guillaume MP, Devriendt J, et al. Fatal liver failure associated with nevirapine in a pregnant HIV patient: the first reported case. Gastroenterol 2000;118 (suppl 2):Abs 6623 (101st Annual Meeting of the American Gastroenterological Association, San Diego, May 21-24, 2000).
  97. Joy S, Poi M, Hughes L, et al. Third-trimester maternal toxicity with nevirapine use in pregnancy. Obstet Gynecol 2005; 106:1032.
  98. Ford N, Calmy A, Andrieux-Meyer I, et al. Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis. AIDS 2013; 27:1135.
  99. Mirochnick M, Siminski S, Fenton T, et al. Nevirapine pharmacokinetics in pregnant women and in their infants after in utero exposure. Pediatr Infect Dis J 2001; 20:803.
  100. Visnegarwala F, Krause KL, Musher DM. Severe diabetes associated with protease inhibitor therapy. Ann Intern Med 1997; 127:947.
  101. Eastone JA, Decker CF. New-onset diabetes mellitus associated with use of protease inhibitor. Ann Intern Med 1997; 127:948.
  102. Dube MP, Sattler FR. Metabolic complications of antiretroviral therapies. AIDS Clin Care 1998; 10:41.
  103. Hitti J, Andersen J, McComsey G, et al. Protease inhibitor-based antiretroviral therapy and glucose tolerance in pregnancy: AIDS Clinical Trials Group A5084. Am J Obstet Gynecol 2007; 196:331.e1.
  104. Tang JH, Sheffield JS, Grimes J, et al. Effect of protease inhibitor therapy on glucose intolerance in pregnancy. Obstet Gynecol 2006; 107:1115.
  105. Watts DH, Balasubramanian R, Maupin RT Jr, et al. Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316. Am J Obstet Gynecol 2004; 190:506.
  106. Tuomala RE, Watts DH, Li D, et al. Improved obstetric outcomes and few maternal toxicities are associated with antiretroviral therapy, including highly active antiretroviral therapy during pregnancy. J Acquir Immune Defic Syndr 2005; 38:449.
  107. Floridia M, Ravizza M, Masuelli G, et al. Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study. J Antimicrob Chemother 2014; 69:1377.
  108. Ripamonti D, Cattaneo D, Maggiolo F, et al. Atazanavir plus low-dose ritonavir in pregnancy: pharmacokinetics and placental transfer. AIDS 2007; 21:2409.
  109. Conradie F, Zorrilla C, Josipovic D, et al. Safety and exposure of once-daily ritonavir-boosted atazanavir in HIV-infected pregnant women. HIV Med 2011; 12:570.
  110. Mirochnick M, Best BM, Stek AM, et al. Atazanavir pharmacokinetics with and without tenofovir during pregnancy. J Acquir Immune Defic Syndr 2011; 56:412.
  111. Eley T, Bertz R, Hardy H, Burger D. Atazanavir pharmacokinetics, efficacy and safety in pregnancy: a systematic review. Antivir Ther 2013; 18:361.
  112. Kreitchmann R, Best BM, Wang J, et al. Pharmacokinetics of an increased atazanavir dose with and without tenofovir during the third trimester of pregnancy. J Acquir Immune Defic Syndr 2013; 63:59.
  113. Furco A, Gosrani B, Nicholas S, et al. Successful use of darunavir, etravirine, enfuvirtide and tenofovir/emtricitabine in pregnant woman with multiclass HIV resistance. AIDS 2009; 23:434.
  114. Ivanovic J, Bellagamba R, Nicastri E, et al. Use of darunavir/ritonavir once daily in treatment-naive pregnant woman: pharmacokinetics, compartmental exposure, efficacy and safety. AIDS 2010; 24:1083.
  115. Jaworsky D, Thompson C, Yudin MH, et al. Use of newer antiretroviral agents, darunavir and etravirine with or without raltegravir, in pregnancy: a report of two cases. Antivir Ther 2010; 15:677.
  116. Colbers A, Moltó J, Ivanovic J, et al. Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women. J Antimicrob Chemother 2015; 70:534.
  117. Zorrilla CD, Wright R, Osiyemi OO, et al. Total and unbound darunavir pharmacokinetics in pregnant women infected with HIV-1: results of a study of darunavir/ritonavir 600/100 mg administered twice daily. HIV Med 2014; 15:50.
  118. Stek A, Best BM, Wang J, et al. Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women. J Acquir Immune Defic Syndr 2015; 70:33.
  119. Stek AM, Mirochnick M, Capparelli E, et al. Reduced lopinavir exposure during pregnancy. AIDS 2006; 20:1931.
  120. Mirochnick M, Best BM, Stek AM, et al. Lopinavir exposure with an increased dose during pregnancy. J Acquir Immune Defic Syndr 2008; 49:485.
  121. Khuong-Josses MA, Azerad D, Boussaïri A, Ekoukou D. Comparison of lopinavir level between the two formulations (soft-gel capsule and tablet) in HIV-infected pregnant women. HIV Clin Trials 2007; 8:254.
  122. Bouillon-Pichault M, Jullien V, Azria E, et al. Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment. J Antimicrob Chemother 2009; 63:1223.
  123. Best BM, Stek AM, Mirochnick M, et al. Lopinavir tablet pharmacokinetics with an increased dose during pregnancy. J Acquir Immune Defic Syndr 2010; 54:381.
  124. Watts DH, Stek A, Best BM, et al. Raltegravir pharmacokinetics during pregnancy. J Acquir Immune Defic Syndr 2014; 67:375.
  125. Blonk MI, Colbers AP, Hidalgo-Tenorio C, et al.. Raltegravir in HIV-1-infected pregnant women: Pharmacokinetics, safety, and efficacy. Clin Infect Dis 2015.