Metabolic and mitochondrial effects of antiretroviral drug exposure in pregnancy and postpartum: Implications for fetal and future health

Dieffenbach, 2011, Thirty years of HIV and AIDS: future challenges and opportunities, Ann Intern Med, 154, 766, 10.7326/0003-4819-154-11-201106070-00345 Connor, 1994, 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, 331, 1173, 10.1056/NEJM199411033311801 Briand, 2009, No relation between in-utero exposure to HAART and intrauterine growth retardation, AIDS, 23, 1235, 10.1097/QAD.0b013e32832be0df Nielsen-Saines, 2012, Infant outcomes after maternal antiretroviral exposure in resource-limited settings, Pediatrics, 129, e1525, 10.1542/peds.2011-2340 Watts, 2004, Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316, Am J Obstet Gynecol, 190, 506, 10.1016/j.ajog.2003.07.018 Aebi-Popp, 2010, Pregnancy and delivery outcomes of HIV infected women in Switzerland 2003–2008, J Perinat Med, 38, 353, 10.1515/jpm.2010.052 Stanley, 2012, Body composition and metabolic changes in HIV-infected patients, J Infect Dis, 205, S383, 10.1093/infdis/jis205 Blanche, 2006, Mitochondrial dysfunction following perinatal exposure to nucleoside analogues, AIDS, 20, 1685, 10.1097/01.aids.0000242814.42344.77 Hulgan, 2012, HIV and mitochondria: more than just drug toxicity, J Infect Dis, 205, 1769, 10.1093/infdis/jis105 Rakhmanina, 2012, Pharmacokinetic considerations of perinatal antiretroviral therapy, Curr Drug Metab, 13, 744, 10.2174/138920012800840365 World Health Organization. Estimated number of women living with HIV needing and receiving antiretroviral medicine for PMTCT in low- and middle-income countries 2010. Available at: http://www.who.int/hiv/data/Table7_5_full.png. Flint, 2009, The role of protease inhibitors in the pathogenesis of HIV-associated lipodystrophy: cellular mechanisms and clinical implications, Toxicol Pathol, 37, 65, 10.1177/0192623308327119 Grinspoon, 2005, Cardiovascular risk and body-fat abnormalities in HIV-infected adults, N Engl J Med, 352, 48, 10.1056/NEJMra041811 Jones, 2005, Impact of antiretroviral choice on hypercholesterolaemia events: the role of the nucleoside reverse transcriptase inhibitor backbone, HIV Med, 6, 396, 10.1111/j.1468-1293.2005.00325.x Dimock, 2011, Longitudinal assessment of metabolic abnormalities in adolescents and young adults with HIV-infection acquired perinatally or in early childhood, Metabolism, 60, 874, 10.1016/j.metabol.2010.08.007 Hadigan, 2001, Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy, Clin Infect Dis, 32, 130, 10.1086/317541 Hazra, 2012, Lipid levels in the second year of life among HIV-infected and HIV-exposed uninfected Latin American children, AIDS, 26, 235, 10.1097/QAD.0b013e32834dc5fc Herrera, 2002, Lipid metabolism in pregnancy and its consequences in the fetus and newborn, Endocrine, 19, 43, 10.1385/ENDO:19:1:43 Woollett, 2005, Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation, Am J Clin Nutr, 82, 1155, 10.1093/ajcn/82.6.1155 Floridia, 2006, Lipid profile during pregnancy in HIV-infected women, HIV Clin Trials, 7, 184, 10.1310/hct0704-184 Senise, 2011, Current treatment strategies, complications and considerations for the use of HIV antiretroviral therapy during pregnancy, AIDS Rev, 13, 198 Toleikyte, 2011, Pregnancy outcomes in familial hypercholesterolemia: a registry-based study, Circulation, 124, 1606, 10.1161/CIRCULATIONAHA.110.990929 Napoli, 2001, Maternal hypercholesterolemia during pregnancy influences the later development of atherosclerosis: clinical and pathogenic implications, Eur Heart J, 22, 4, 10.1053/euhj.2000.2147 Goldberg, 2012, Severe hypertriglyceridemia in pregnancy, J Clin Endocrinol Metab, 97, 2589, 10.1210/jc.2012-1250 Catov, 2010, Prepregnancy lipids related to preterm birth risk: the coronary artery risk development in young adults study, J Clin Endocrinol Metab, 95, 3711, 10.1210/jc.2009-2028 Mudd, 2012, Maternal lipids at mid-pregnancy and the risk of preterm delivery, Acta Obstet Gynecol Scand, 91, 726, 10.1111/j.1600-0412.2012.01391.x Schulte, 2007, 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, 119, e900, 10.1542/peds.2006-1123 Powis, 2011, Increased risk of preterm delivery among HIV-infected women randomized to protease versus nucleoside reverse transcriptase inhibitor-based HAART during pregnancy, J Infect Dis, 204, 506, 10.1093/infdis/jir307 Grunfeld, 1992, Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome, J Clin Endocrinol Metab, 74, 1045, 10.1210/jc.74.5.1045 Estrada, 2011, Dyslipidemia related to antiretroviral therapy, AIDS Rev, 13, 49 Mencarelli, 2010, The bile acid sensor FXR protects against dyslipidemia and aortic plaques development induced by the HIV protease inhibitor ritonavir in mice, PLoS One, 5, e13238, 10.1371/journal.pone.0013238 Tien, 2012, Association of HIV infection with incident diabetes mellitus: impact of using hemoglobin A1C as a criterion for diabetes, J Acquir Immune Defic Syndr, 10.1097/QAI.0b013e31826bfc32 Haugaard, 2005, Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells, Eur J Endocrinol, 152, 103, 10.1530/eje.1.01835 Geffner, 2011, Factors associated with insulin resistance among children and adolescents perinatally infected with HIV-1 in the pediatric HIV/AIDS cohort study, Horm Res Paediatr, 76, 386, 10.1159/000332957 International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. IDF; 2006. Available at: http://www.idf.org/metabolic-syndrome. Aldrovandi, 2009, Morphologic and metabolic abnormalities in vertically HIV-infected children and youth, AIDS, 23, 661, 10.1097/QAD.0b013e3283269dfb Gutierrez, 2012, Dysregulation of glucose metabolism in HIV patients: epidemiology, mechanisms, and management, Endocrine, 41, 1, 10.1007/s12020-011-9565-z Murata, 2000, The mechanism of insulin resistance caused by HIV protease inhibitor therapy, J Biol Chem, 275, 20251, 10.1074/jbc.C000228200 Rondanelli, 2004, Endocrine pancreatic dysfunction in HIV-infected children: association with growth alterations, J Infect Dis, 190, 908, 10.1086/422255 Schwarz, 2004, Indinavir increases glucose production in healthy HIV-negative men, AIDS, 18, 1852, 10.1097/00002030-200409030-00017 Hruz, 2011, Molecular mechanisms for insulin resistance in treated HIV-infection, Best Pract Res Clin Endocrinol Metab, 25, 459, 10.1016/j.beem.2010.10.017 Dahlgren, 2006, Pregnancy and insulin resistance, Metab Syndr Relat Disord, 4, 149, 10.1089/met.2006.4.149 Stevenson, 2005 Krakowiak, 2012, Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders, Pediatrics, 129, e1121, 10.1542/peds.2011-2583 National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics; 2011. Available at: http://diabetes.niddk.nih.gov.proxygw.wrlc.org/dm/pubs/statistics/#Gestational. Gonzalez-Tome, 2008, Gestational diabetes mellitus in a cohort of HIV-1 infected women, HIV Med, 9, 868, 10.1111/j.1468-1293.2008.00639.x Marti, 2007, Obstetric and perinatal complications in HIV-infected women. Analysis of a cohort of 167 pregnancies between 1997 and 2003, Acta Obstet Gynecol Scand, 86, 409, 10.1080/00016340601148531 Ehrlich, 2012, Pregnancy glucose levels in women without diabetes or gestational diabetes and childhood cardiometabolic risk at 7 years of age, J Pediatr, 10.1016/j.jpeds.2012.05.049 Metzger, 2008, Hyperglycemia and adverse pregnancy outcomes, N Engl J Med, 358, 1991, 10.1056/NEJMoa0707943 Meloni, 2011, Glucose plasma levels and pregnancy outcomes in women with HIV, HIV Clin Trials, 12, 299, 10.1310/hct1206-299 Kershnar, 2006, Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: the SEARCH for Diabetes in Youth Study, J Pediatr, 149, 314, 10.1016/j.jpeds.2006.04.065 Shafrir, 1982, Maternal–fetal fat transport versus new fat synthesis in the pregnant diabetic rat, Diabetologia, 22, 111, 10.1007/BF00254839 Ervin, 2009, Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006, Natl Health Stat Report, 1 Madhra, 2012, A complicated pregnancy in a patient with lipodystrophic diabetes attributable to a peroxisome proliferator-activated receptor gamma (PPARG) mutation, Diabet Med, 29, e398, 10.1111/j.1464-5491.2012.03742.x Apostolova, 2011, Mitochondrial interference by anti-HIV drugs: mechanisms beyond Pol-gamma inhibition, Trends Pharmacol Sci, 32, 715, 10.1016/j.tips.2011.07.007 Blas-Garcia, 2010, Inhibition of mitochondrial function by efavirenz increases lipid content in hepatic cells, Hepatology, 52, 115, 10.1002/hep.23647 Lewis, 2003, Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective, Nat Rev Drug Discov, 2, 812, 10.1038/nrd1201 Calmy, 2009, A new era of antiretroviral drug toxicity, Antivir Ther, 14, 165 Arnaudo, 1991, Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy, Lancet, 337, 508, 10.1016/0140-6736(91)91294-5 Foster, 2007, HIV and mitochondrial toxicity in children, J Antimicrob Chemother, 61, 8, 10.1093/jac/dkm411 Maagaard, 2009, Long term adverse effects related to nucleoside reverse transcriptase inhibitors: clinical impact of mitochondrial toxicity, Scand J Infect Dis, 41, 808, 10.3109/00365540903186181 Payne, 2011, Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations, Nat Genet, 43, 806, 10.1038/ng.863 Noguera, 2003, Hyperlactatemia in human immunodeficiency virus-infected children receiving antiretroviral treatment, Pediatr Infect Dis J, 22, 778, 10.1097/01.inf.0000083826.11124.b1 Scalfaro, 1998, Severe transient neonatal lactic acidosis during prophylactic zidovudine treatment, Intensive Care Med, 24, 247, 10.1007/s001340050558 Blanche, 1999, Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues, Lancet, 354, 1084, 10.1016/S0140-6736(99)07219-0 Divi, 2005, Cardiac mitochondrial compromise in 1-yr-old Erythrocebus patas monkeys perinatally-exposed to nucleoside reverse transcriptase inhibitors, Cardiovasc Toxicol, 5, 333, 10.1385/CT:5:3:333 Heidari, 2011, Antiretroviral drugs for preventing mother-to-child transmission of HIV: a review of potential effects on HIV-exposed but uninfected children, J Acquir Immune Defic Syndr, 57, 290, 10.1097/QAI.0b013e318221c56a Miller, 2012, Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children, HIV Med, 13, 264, 10.1111/j.1468-1293.2011.00970.x Blanche, 1989, A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. HIV Infection in Newborns French Collaborative Study Group, N Engl J Med, 320, 1643, 10.1056/NEJM198906223202502 Dagan, 2002, Mitochondrial dysfunction and antiretroviral nucleoside analog toxicities: what is the evidence?, Mitochondrion, 1, 397, 10.1016/S1567-7249(02)00003-X Kamemoto, 2004, HIV-associated mitochondrial toxicity in pregnancy, Mitochondrion, 4, 153, 10.1016/j.mito.2004.05.011 Hernandez, 2012, Perinatal outcomes, mitochondrial toxicity and apoptosis in HIV-treated pregnant women and in-utero-exposed newborn, AIDS, 26, 419, 10.1097/QAD.0b013e32834f3232 Kirmse, 2012, Abnormal newborn screening data and acylcarnitines in HIV/ARV-exposed infants, Pediatr Infect Dis J Igoudjil, 2008, High concentrations of stavudine impair fatty acid oxidation without depleting mitochondrial DNA in cultured rat hepatocytes, Toxicol In Vitro, 22, 887, 10.1016/j.tiv.2008.01.011 Wilcken, 2010, Fatty acid oxidation disorders: outcome and long-term prognosis, J Inherit Metab Dis, 33, 501, 10.1007/s10545-009-9001-1 Patterson, 2009, Human urinary metabolomic profile of PPARalpha induced fatty acid beta-oxidation, J Proteome Res, 8, 4293, 10.1021/pr9004103 Dunning, 2010, Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development, Biol Reprod, 83, 909, 10.1095/biolreprod.110.084145 Hicks, 1995, Heterozygosity for long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency and deterioration in liver function in a newborn infant infected with human immunodeficiency virus, J Pediatr, 127, 599, 10.1016/S0022-3476(95)70122-2 Ibdah, 2000, Liver disease in pregnancy and fetal fatty acid oxidation defects, Mol Genet Metab, 71, 182, 10.1006/mgme.2000.3065 Sims, 1995, The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy, Proc Natl Acad Sci U S A, 92, 841, 10.1073/pnas.92.3.841 Ollenschlager, 1988, Plasma amino acid pattern of patients with HIV infection, Clin Chem, 34, 1787, 10.1093/clinchem/34.9.1781 Zangerle, 2010, Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy, Brain Behav Immun, 24, 403, 10.1016/j.bbi.2009.11.004 Prick, 2012, Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: pregnancy complications and neonatal sequelae in untreated and treated pregnancies, Am J Clin Nutr, 95, 374, 10.3945/ajcn.110.009456 Teissier, 2012, Maternal phenylketonuria: low phenylalaninemia might increase the risk of intra uterine growth retardation, J Inherit Metab Dis, 10.1007/s10545-012-9491-0 Levy, 1994, Maternal mild hyperphenylalaninaemia: an international survey of offspring outcome, Lancet, 344, 1589, 10.1016/S0140-6736(94)90404-9 Reeds, 2006, Whole-body proteolysis rate is elevated in HIV-associated insulin resistance, Diabetes, 55, 2849, 10.2337/db06-0255 Sim, 2002, Acylcarnitine profiles in fibroblasts from patients with respiratory chain defects can resemble those from patients with mitochondrial fatty acid β-oxidation disorders, Metabolism, 51, 366, 10.1053/meta.2002.30521 Wang, 2010, Evidence for physical association of mitochondrial fatty acid oxidation and oxidative phosphorylation complexes, J Biol Chem, 285, 29834, 10.1074/jbc.M110.139493 Mallon, 2005, In vivo, nucleoside reverse-transcriptase inhibitors alter expression of both mitochondrial and lipid metabolism genes in the absence of depletion of mitochondrial DNA, J Infect Dis, 191, 1686, 10.1086/429697 Feeney, 2010, Impact of mitochondrial toxicity of HIV-1 antiretroviral drugs on lipodystrophy and metabolic dysregulation, Curr Pharm Des, 16, 3339, 10.2174/138161210793563482 Petersen, 2004, Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes, N Engl J Med, 350, 664, 10.1056/NEJMoa031314 Maassen, 2004, Mitochondrial diabetes: molecular mechanisms and clinical presentation, Diabetes, 53, S103, 10.2337/diabetes.53.2007.S103 Chinnery, 2000, Mitochondrial disorders overview Liou, 2012, Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes mellitus, Diabetes, 61, 2642, 10.2337/db11-1369 Blas-Garcia, 2011, Oxidative stress and mitochondrial impairment after treatment with anti-HIV drugs: clinical implications, Curr Pharm Des, 17, 4076, 10.2174/138161211798764951 Bialkowska, 2000, Oxidative DNA damage in fetal tissues after transplacental exposure to 3'-azido-3'-deoxythymidine (AZT), Carcinogenesis, 21, 1059, 10.1093/carcin/21.5.1059 Rinaudo, 2012, Fetal programming and metabolic syndrome, Annu Rev Physiol, 74, 107, 10.1146/annurev-physiol-020911-153245 Whincup, 2008, Birth weight and risk of type 2 diabetes: a systematic review, JAMA, 300, 2886, 10.1001/jama.2008.886 Durnwald, 2012, Fetal links to chronic disease: the role of gestational diabetes mellitus, Am J Perinatol Napoli, 1997, Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions, J Clin Invest, 100, 2680, 10.1172/JCI119813 Vo, 2012, Molecular mechanisms underlying the fetal programming of adult disease, J Cell Commun Signal, 6, 139, 10.1007/s12079-012-0165-3 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, 2011. Available at: http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Wobeser, 2012, Macrocytosis is a predictor of resting lactate concentrations in persons on dideoxynucleoside therapy for HIV infection, Int J Infect Dis, 16, e225, 10.1016/j.ijid.2011.11.013 Arenas-Pinto, 2012, Common inherited mitochondrial DNA mutations and nucleoside reverse transcriptase inhibitor-induced severe hyperlactataemia in HIV-infected adults: an exploratory study, Antivir Ther, 17, 275, 10.3851/IMP1947 Feeney, 2011, Hyperlactataemia in HIV-infected subjects initiating antiretroviral therapy in a large randomized study (a substudy of the INITIO trial), HIV Med, 12, 602, 10.1111/j.1468-1293.2011.00934.x Haas, 2008, The in-depth evaluation of suspected mitochondrial disease, Mol Genet Metab, 94, 16, 10.1016/j.ymgme.2007.11.018