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Current Treatment Options in Neurology

, Volume 15, Issue 4, pp 529–543 | Cite as

Safe Treatment of Seizures in the Setting of HIV/AIDS

  • Omar SiddiqiEmail author
  • Gretchen L. Birbeck
EPILEPSY (E WATERHOUSE, SECTION EDITOR)

Opinion statement

HIV+ patients are at increased risk for developing seizures due to the vulnerability of the central nervous system to HIV-associated diseases, immune dysfunction, and metabolic disturbances. In patients with acute seizures, standard protocols still apply with urgent seizure cessation being the priority. Management of the person with established epilepsy who contracts HIV is challenging, but the decision to initiate chronic antiepileptic drug (AED) therapy in an HIV+ patient is also difficult. Chronic treatment guidelines emphasize the interactions between AEDs and antiretroviral (ARV) medications, but provide no explicit advice regarding when to initiate an AED, what medication to select, and/or the duration of treatment. Epidemiologic data regarding seizure recurrence risk in HIV+ individuals is not available. The risk of further seizures likely depends upon the underlying etiology for the seizure(s) and patients’ immune status and may be increased by the use of efavirenz (an ARV). The issues for consideration include AED-ARV interactions, organ dysfunction, seizure type, and drug side effects, which may worsen or be confused with symptoms of HIV and/or epilepsy. Co-administration of enzyme inducing (EI)-AEDs and ARVs can result in virological failure, breakthrough seizure activity, AED toxicity, and/or ARV toxicity. Where available, the AED of choice in HIV+ patients is levetiracetam due to its broad spectrum activity, ease of use, minimal drug interactions, and favorable side effect profile. Lacosamide, gabapentin, and pregabalin are also favored choices in patients with partial onset seizures and/or those failing levetiracetam. Where newer AEDs are not available, valproic acid may be the treatment of choice in terms of an AED, which will not cause enzyme induction-associated ARV failure, but its side effect profile causes other obvious problems. In resource-limited settings (RLS) where only EI-AEDs are available, there are no good treatment options and further pressure needs to be placed upon policymakers to address this care gap and public health threat.

Keywords

Seizure Epilepsy HIV AIDS Antiepileptic drugs Antiretroviral medications Highly active antiretroviral therapy Opportunistic infections Treatment Safe treatment Cerebrovascular disease HIV viremia Acute management Chronic management 

Notes

Acknowledgment

Gretchen L. Birbeck has received grant support from the National Institutes of Health.

Conflict of Interest

Omar Siddiqi declares that he has no conflict of interest.

Gretchen L. Birbeck has served on a board for Lifting the Burden.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    WHO. Gobal Summary of the AIDS epidemic 2011. 2011. Available at: http://www.who.int/hiv/data/2012_epi_core_en.png Accessed February 9, 2013.
  2. 2.
    UNAIDS. UNAIDS United States of America. 2013. Available at: http://www.unaids.org/en/regionscountries/countries/unitedstatesofamerica/ Accessed February 9, 2013.
  3. 3.
    Aarli JA, Diop AG, Lochmuller H. Neurology in sub-Saharan Africa: a challenge for World Federation of Neurology. Neurology. 2007;69(17):1715–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Sinha S, Satishchandra P, Nalini A, et al. New-onset seizures among HIV infected drug naïve patients from south India. Neuro Asia. 2005;10:29–33.Google Scholar
  5. 5.
    Kellinghaus C, Engbring C, Kovac S, et al. Frequency of seizures and epilepsy in neurological HIV-infected patients. Seizure. 2008;17(1):27–33.PubMedCrossRefGoogle Scholar
  6. 6.••
    Birbeck GL, French JA, Perucca E, et al. Evidence-based guideline: antiepileptic drug selection for people with HIV/AIDS: report of the Quality Standards Subcommittee of the American Academy of Neurology. and the Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy. Neurology. 2012;78(2):139–45. This evidence-based guideline which was jointly endorsed by the American Academy of Neurology, the World Health Organization and the American Epilepsy Society provides a detailed review of the information to date on drug interactions between AEDs and ARVs as well as graded classification of the evidence.PubMedCrossRefGoogle Scholar
  7. 7.
    Bhanushali MJ, Helmers SJ. Diagnosis and acute management of seizures in adults. Hosp Phys. 2008;48:37–42.Google Scholar
  8. 8.
    Berenguer J, Moreno S, Laguna F, et al. Tuberculous meningitis in patients infected with the human immunodeficiency virus. N Engl J Med. 1992;326(10):668–72.PubMedCrossRefGoogle Scholar
  9. 9.
    Marx GE, Chan ED. Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat. 2011;2011:798764.PubMedGoogle Scholar
  10. 10.
    Garcia-Monco JC. Central nervous system tuberculosis. Neurol Clin. 1999;17(4):737–59.PubMedCrossRefGoogle Scholar
  11. 11.
    Bharucha NE, Raven RH, Nambiar VK. Review of seizures and status epilepticus in HIV and tuberculosis with preliminary view of Bombay hospital experience. Epilepsia. 2009;50 Suppl 12:64–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Kennedy DH, Fallon RJ. Tuberculous meningitis. JAMA. 1979;241(3):264–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Sutlas PN, Unal A, Forta H, et al. Tuberculous meningitis in adults: review of 61 cases. Infection. 2003;31(6):387–91.PubMedGoogle Scholar
  14. 14.
    Mora DJ, da Cunha Colombo ER, Ferreira-Paim K, et al. Clinical, epidemiological and outcome features of patients with cryptococcosis in Uberaba, Minas Gerais, Brazil. Mycopathologia. 2012;173(5–6):321–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Dore GJ, Law MG, Brew BJ. Prospective analysis of seizures occurring in human immunodeficiency virus type-1 infection. J Neuro-AIDS. 1996;1(4):59–69.CrossRefGoogle Scholar
  16. 16.
    Wong MC, Suite ND, Labar DR. Seizures in human immunodeficiency virus infection. Arch Neurol. 1990;47(6):640–2.PubMedCrossRefGoogle Scholar
  17. 17.
    Lima MA, Drislane FW, Koralnik IJ. Seizures and their outcome in progressive multifocal leukoencephalopathy. Neurology. 2006;66(2):262–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Glassock RJ, Cohen AH, Danovitch G, Parsa KP. Human immunodeficiency virus (HIV) infection and the kidney. Ann Intern Med. 1990;112(1):35–49.PubMedCrossRefGoogle Scholar
  19. 19.
    Tang WW, Kaptein EM, Feinstein EI, Massry SG. Hyponatremia in hospitalized patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex. Am J Med. 1993;94(2):169–74.PubMedCrossRefGoogle Scholar
  20. 20.
    Vitting KE, Gardenswartz MH, Zabetakis PM, et al. Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome. JAMA. 1990;263(7):973–8.PubMedCrossRefGoogle Scholar
  21. 21.••
    Benjamin LA, Bryer A, Emsley HC, et al. HIV infection and stroke: current perspectives and future directions. Lancet Neurol. 2012;11(10):878–90. This is an excellent review of the epidemiology and pathophysiology of stroke in people with HIV, which also offers considerations for future research directions.PubMedCrossRefGoogle Scholar
  22. 22.
    Nijhawan AE, Zachary KC, Kwara A, Venna N. Status epilepticus resulting from severe efavirenz toxicity in an HIV-infected patient. AIDS Read. 2008;18(7):386–8. C383.PubMedGoogle Scholar
  23. 23.
    Strehlau R, Martens L, Coovadia A, et al. Absence seizures associated with efavirenz initiation. Pediatr Infect Dis J. 2011;30(11):1001–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Burger D, van der Heiden I, la Porte C, et al. Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism. Br J Clin Pharmacol. 2006;61(2):148–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Gandhi M, Greenblatt RM, Bacchetti P, et al. A single-nucleotide polymorphism in CYP2B6 leads to >3-fold increases in efavirenz concentrations in plasma and hair among HIV-infected women. J Infect Dis. 2012;206(9):1453–61.PubMedCrossRefGoogle Scholar
  26. 26.
    Nyakutira C, Roshammar D, Chigutsa E, et al. High prevalence of the CYP2B6 516G– > T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe. Eur J Clin Pharmacol. 2008;64(4):357–65.PubMedCrossRefGoogle Scholar
  27. 27.
    Ward BA, Gorski JC, Jones DR, et al. The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther. 2003;306(1):287–300.PubMedCrossRefGoogle Scholar
  28. 28.
    Holtzman DM, Kaku DA, So YT. New-onset seizures associated with human immunodeficiency virus infection: causation and clinical features in 100 cases. Am J Med. 1989;87(2):173–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Portegies P, Berger JR. HIV/AIDS and the nervous system. Edinburgh: Elsevier; 2007.Google Scholar
  30. 30.
    Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE. Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol. 2005;64(6):529–36.PubMedGoogle Scholar
  31. 31.
    Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol. 2006;147 Suppl 1:S232–40.PubMedGoogle Scholar
  32. 32.
    Ravizza T, Balosso S, Vezzani A. Inflammation and prevention of epileptogenesis. Neurosci Lett. 2011;497(3):223–30.PubMedCrossRefGoogle Scholar
  33. 33.
    AIDSinfo. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2013. Available at: http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/. Accessed Februrary 18, 2013.
  34. 34.
    Lowenstein DH. Status epilepticus: an overview of the clinical problem. Epilepsia. 1999;40 Suppl 1:S3–8. discussion S21–2.PubMedCrossRefGoogle Scholar
  35. 35.
    Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. 1999;40(1):120–2.PubMedCrossRefGoogle Scholar
  36. 36.
    Beghi E. Treating epilepsy across its different stages. Ther Adv Neurol Disord. 2010;3(2):85–92.PubMedCrossRefGoogle Scholar
  37. 37.
    Berg AT. Risk of recurrence after a first unprovoked seizure. Epilepsia. 2008;49 Suppl 1:13–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology. 1991;41(7):965–72.PubMedCrossRefGoogle Scholar
  39. 39.
    Kim LG, Johnson TL, Marson AG, Chadwick DW, MMS. Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial. Lancet Neurol. 2006;5(4):317–22.PubMedCrossRefGoogle Scholar
  40. 40.
    L'Homme RF, Dijkema T, van der Ven AJ, Burger DM. Brief report: enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women. J Acquir Immune Defic Syndr. 2006;43(2):193–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Ji P, Damle B, Xie J, Unger SE, et al. Pharmacokinetic interaction between efavirenz and carbamazepine after multiple-dose administration in healthy subjects. J Clin Pharmacol. 2008;48(8):948–56.PubMedCrossRefGoogle Scholar
  42. 42.
    Okulicz JF, Grandits GA, French JA, et al. Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study. AIDS Res Ther. 2011;8:18.PubMedCrossRefGoogle Scholar
  43. 43.
    Jennings HR, Romanelli F. The use of valproic acid in HIV-positive patients. Ann Pharmacother. 1999;33(10):1113–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Romanelli F, Jennings HR, Nath A, et al. Therapeutic dilemma: the use of anticonvulsants in HIV-positive individuals. Neurology. 2000;54(7):1404–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Moog C, Kuntz-Simon G, Caussin-Schwemling C, Obert G. Sodium valproate, an anticonvulsant drug, stimulates human immunodeficiency virus type 1 replication independently of glutathione levels. J Gen Virol. 1996;77(Pt 9):1993–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Witvrouw M, Schmit JC, Van Remoortel B, et al. Cell type-dependent effect of sodium valproate on human immunodeficiency virus type 1 replication in vitro. AIDS Res Hum Retrovir. 1997;13(2):187–92.PubMedCrossRefGoogle Scholar
  47. 47.
    Sagot-Lerolle N, Lamine A, Chaix ML, et al. Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir. AIDS. 2008;22(10):1125–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Yacoob Y, Bhigjee AI, Moodley P, Parboosing R. Sodium valproate and highly active antiretroviral therapy in HIV positive patients who develop new onset seizures. Seizure. 2011;20(1):80–2.PubMedCrossRefGoogle Scholar
  49. 49.
    DiCenzo R, Peterson D, Cruttenden K, et al. Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother. 2004;48(11):4328–31.PubMedCrossRefGoogle Scholar
  50. 50.
    Lertora JJ, Rege AB, Greenspan DL, et al. Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 1994;56(3):272–8.PubMedCrossRefGoogle Scholar
  51. 51.
    van der Lee MJ, Dawood L, ter Hofstede HJ, et al. Lopinavir/ritonavir reduces lamotrigine plasma concentrations in healthy subjects. Clin Pharmacol Ther. 2006;80(2):159–68.PubMedCrossRefGoogle Scholar
  52. 52.
    van Luin M, Colbers A, Verwey-van Wissen CP, et al. The effect of raltegravir on the glucuronidation of lamotrigine. J Clin Pharmacol. 2009;49(10):1220–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Naccarato M, Yoong D, Kovacs C, Gough K. A case of a potential drug interaction between clobazam and etravirine-based antiretroviral therapy. Antivir Ther. 2012;17(3):589–92.PubMedCrossRefGoogle Scholar
  54. 54.
    Sills G, Brodie M. Pharmacokinetics and drug interactions with zonisamide. Epilepsia. 2007;48(3):435–41.PubMedCrossRefGoogle Scholar
  55. 55.
    Barry M, Gibbons S, Back D, Mulcahy F. Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharmacokinet. 1997;32(3):194–209.PubMedCrossRefGoogle Scholar
  56. 56.
    Barry M, Mulcahy F, Merry C, et al. Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection. Clin Pharmacokinet. 1999;36(4):289–304.PubMedCrossRefGoogle Scholar
  57. 57.
    Tseng AL, Foisy MM. Significant interactions with new antiretrovirals and psychotropic drugs. Ann Pharmacother. 1999;33(4):461–73.PubMedCrossRefGoogle Scholar
  58. 58.
    Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol. 2003;2(8):473–81.PubMedCrossRefGoogle Scholar
  59. 59.
    Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol. 2003;2(6):347–56.PubMedCrossRefGoogle Scholar
  60. 60.
    Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2006;61(3):246–55.PubMedCrossRefGoogle Scholar
  61. 61.
    Liedtke MD, Lockhart SM, Rathbun RC. Anticonvulsant and antiretroviral interactions. Ann Pharmacother. 2004;38(3):482–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Hachad H, Ragueneau-Majlessi I, Levy RH. New antiepileptic drugs: review on drug interactions. Ther Drug Monit. 2002;24(1):91–103.PubMedCrossRefGoogle Scholar
  63. 63.
    White JR, Walczak TS, Leppik IE, et al. Discontinuation of levetiracetam because of behavioral side effects: a case–control study. Neurology. 2003;61(9):1218–21.PubMedCrossRefGoogle Scholar
  64. 64.
    Krause LU, Brodowski KO, Kellinghaus C. Atrioventricular block following lacosamide intoxication. Epilepsy Behav. 2011;20(4):725–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Nizam A, Mylavarapu K, Thomas D, et al. Lacosamide-induced second-degree atrioventricular block in a patient with partial epilepsy. Epilepsia. 2011;52(10):e153–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Halford JJ, Lapointe M. Clinical perspectives on lacosamide. Epilepsy Curr. 2009;9(1):1–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Zaccara G, Perucca P, Loiacono G, et al. The adverse event profile of lacosamide: a systematic review and meta-analysis of randomized controlled trials. Epilepsia. 2013;54(1):66–74.PubMedCrossRefGoogle Scholar
  68. 68.
    McLean MJ, Gidal BE. Gabapentin dosing in the treatment of epilepsy. Clin Ther. 2003;25(5):1382–406.PubMedCrossRefGoogle Scholar
  69. 69.
    McLean MJ. Clinical pharmacokinetics of gabapentin. Neurology. 1994;44(6 Suppl 5):S17–22. discussion S31–12.PubMedGoogle Scholar
  70. 70.
    Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004;45 Suppl 6:13–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Picot MC, Neveu D, Kahane P, et al. Cost-effectiveness of epilepsy surgery in a cohort of patients with medically intractable partial epilepsy—preliminary results. Rev Neurol. 2004;160(Spec No 1):5S354–67.PubMedGoogle Scholar
  72. 72.
    Silfvenius H. Cost and cost-effectiveness of epilepsy surgery. Epilepsia. 1999;40 Suppl 8:32–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Widjaja E, Li B, Schinkel CD, et al. Cost-effectiveness of pediatric epilepsy surgery compared with medical treatment in children with intractable epilepsy. Epilepsy Res. 2011;94(1–2):61–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Englot DJ, Chang EF, Auguste KI. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg. 2011;115(6):1248–55.PubMedCrossRefGoogle Scholar
  75. 75.
    Boon P, Vonck K, D'Have M, et al. Cost-benefit of vagus nerve stimulation for refractory epilepsy. Acta Neurol Belg. 1999;99(4):275–80.PubMedGoogle Scholar
  76. 76.
    Majoie HJ, Berfelo MW, Aldenkamp AP, et al. Vagus nerve stimulation in children with therapy-resistant epilepsy diagnosed as Lennox-Gastaut syndrome: clinical results, neuropsychological effects, and cost-effectiveness. J Clin Neurophysiol. 2001;18(5):419–28.PubMedCrossRefGoogle Scholar
  77. 77.
    Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007;48(1):43–58.PubMedCrossRefGoogle Scholar
  78. 78.
    Kossoff EH, Rowley H, Sinha SR, Vining EP. A prospective study of the modified Atkins diet for intractable epilepsy in adults. Epilepsia. 2008;49(2):316–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Beth Israel Deaconess Medical CenterBostonUSA
  2. 2.University of Zambia School of Medicine, c/o Epilepsy Associated Stigma in ZambiaLusakaZambia
  3. 3.Michigan State UniversityEast LansingUSA

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