Should antiretroviral therapy for HIV infection be tailored for intracerebral penetration?

Netherlands Journal of Medicine

Volumn 67, Issue 6, 2009, Pages 206-211

  Koopmans, P P ^a   Ellis, R ^b   Best, B M ^c,d   Letendre, S ^b  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

Antiretroviral drug; Central nervous system; HIV; Penetration

Indexed keywords

ABACAVIR; AMPRENAVIR; ANTIRETROVIRUS AGENT; ATAZANAVIR; DARUNAVIR; DELAVIRDINE; DIDANOSINE; EFAVIRENZ; EMTRICITABINE; ENFUVIRTIDE; ETRAVIRINE; INDINAVIR; LAMIVUDINE; LOPINAVIR; MARAVIROC; NELFINAVIR; NEVIRAPINE; RALTEGRAVIR; RITONAVIR; SAQUINAVIR; STAVUDINE; TENOFOVIR; TIPRANAVIR; ZALCITABINE; ZIDOVUDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

BRAIN FUNCTION; BRAIN TOXICITY; CELL COMPARTMENTALIZATION; DISEASE SEVERITY; GENE MUTATION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MIXED INFECTION; NEUROLOGIC DISEASE; NONHUMAN; REVIEW; VIRUS REPLICATION; BLOOD BRAIN BARRIER; CHEMICALLY INDUCED; COGNITION; COGNITION DISORDERS; DRUG EFFECTS; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1; RISK FACTOR;

ANTI-HIV AGENTS; ANTI-RETROVIRAL AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; BLOOD-BRAIN BARRIER; COGNITION; COGNITION DISORDERS; HIV INFECTIONS; HIV-1; HUMANS; RISK FACTORS;

EID: 68149179492     PISSN: 03002977     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (75)

1. McArthur JC. Neurological complications of HIV infection. Lancet Neurology. 2005;4:543-552
2. Davis LE, Hjelle BL, Miller VE, et al. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology. 1992;42:1736-1739
3. Antinori A, Arendt C, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69:1789-1799 (Pubitemid 350059308)
4. D'Arminio Monforte A, Cinque P, Mocroft A, et al. Changing incidence of central nervous system diseases in the EuroSIDA cohort. Ann Neurol. 2004;55:320-328 (Pubitemid 38292033)
5. Sidtis JJ, Gatsonis C, Price RW, et al. Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group. Ann Neurol. 1993;33:343-349
6. Munoz-Moreno JA, Fumaz CR, Ferrer MJ, et al. Nadir CD4 cell count predicts neurocognitive impairment in HIV infected patienst. Aids Res Hum Retroviruses. 2008;24:1301-1307
7. Riedel DJ, Pardo CA, McArthur J, Nath A. Therapy insight: CNS manifestations of HIV associated immune reconstitution inflammatory syndrome. Nat Cli Pract Neurol. 2006;2:557-565 (Pubitemid 44445811)
8. Forton DM, Akksop JM, Main J, et al. Evidence for a cerebral effect of the hepatitis C virus. Lancet. 2001;358:38-39 (Pubitemid 32709741)
9. Ryan EL, Morgello S, Isaacs K, et al. Neuropsychiatric impact of hepatitis C on advanced HIV. Neurology. 2004;62:957-962 (Pubitemid 38435785)
10. Letendre SL, Cherner M, Ellis RJ, et al. The effects of hepatitis C, HIV and methamphetamine dependence on neuropsychological performance: biological correlates of disease. AIDS. 2005;19(suppl 3):S72-8.
11. Valcour V, Paul R. HIV Infection and dementia in older adults. Clin Infect Dis. 2006;42:1449-1454
12. Price RW, Yiannoutsos CT, Clifford DB, et al. Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trials Group and Neurological AIDS Research Consortium Study Team. AIDS. 1999;13:1677-1685
13. Marra CM, Lockhart D, Zunt JR, Perrin M, Coombs RW, Collier AC. Changes in CSF and plasma HIV-1 RNA and cognition after starting potent antiretroviral therapy. Neurology. 2003;60:1388-1390 (Pubitemid 36461005)
14. Brew BJ, Halman M, Catalan J, et al. Factors in AIDS dementia complex trial design: results and lessons from the abacavir trial. PLoS Clin Trials. 2007;2:13. (Pubitemid 46851656)
15. Pilcher CD, Shugars DC, Fiscus SA, et al. HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health. AIDS. 2001;15:837-845
16. Ellis RJ, Hsia K, Spector SA, et al. Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral Research Center Group. Ann Neurol. 1997;42:679-688
17. De Luca A, Ciancio BC, Larussa D, et al. Correlates of independent HIV-1 replication in the CNS and of its controls by antiretrovirals. Neurology. 2002;59:543-555 (Pubitemid 34857925)
18. McArthur JC, McClernon DR, Cronin MF, et al. Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann Neurol. 1997;42:689-698 (Pubitemid 27481540)
19. Spudich SS, Nilsson AC, Lollo ND, et al. Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC Infect Dis. 2005;5:98.
20. Eggers C, Hertogs K, Sturenburg HJ, van Lunzen J, Stellbrink HJ. Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with viral drug resistance or poor central nervous system drug penetration. AIDS. 2003;17:1897-1906 (Pubitemid 37070275)
21. Spudich S, Lollo N, Liegler T, Deeks SG, Price RW. Treatment benefit on cerebrospinal fluid HIV-1 levels in the setting of systemic virological suppression and failure. J Infect Dis. 2006;194:1686-1696 (Pubitemid 44901999)
22. Ritola K, Pilcher CD, Fiscus SA, et al. Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type 1. J Virol. 2004;78:11208-11218 (Pubitemid 39299660)
23. Harrington PR, Haas DW, Ritola K, Swanstrom R. Compartmentalized human immunodeficiency virus type 1 present in cerebrospinal fluid is produced by short-lived cells. J Virol. 2005;79:7959-7966 (Pubitemid 40853500)
24. Ritola K, Robertson K, Fiscus SA, Hall C, Swanstrom R. Increased human immunodeficiency virus type 1 (HIV-1 env compartmentalization in the presence of HIV-1-associated dementia. J Virol. 2005;79:10830-4.
25. Harrington PR, Schnell, Letendre SL, et al. Cross sectional characterization of HIV-1 env compartimentalization in cerebrospinal fluid over the full disease course. J Virol. 2009; in press.
26. Pillai SK, Pond SL, Liu Y, et al. Genetc attributes of cerebrospinal fluid derived HIB-1 env. Brain. 2006;129:1872-1883
27. Wong JK, Ignacio CC, Torriani F, et al. In vivo compartimentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues. J Virol. 1997;71:2059-2071
28. Strain MC, Letendre S, Pillai SK, et al. Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy. J Virol. 2005;79:1772-1788 (Pubitemid 40459123)
29. Cunningham PH, Smith DG, Satchell C, Cooper DA, Brew B. Evidence for independent development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid. AIDS. 2000;14:1949-1954 (Pubitemid 30688589)
30. Lanier ER, Sturge G, McClernon D, et al. HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with abacavir. AIDS. 2001;15:747-751 (Pubitemid 32423222)
31. Di Stefano M, Sabri F, Leitner T, et al. Reverse transcriptase sequence of paired isolates of cerebrospinal fluid and blood from patients infected with human immunodeficiency virus type 1 during zidovudine treatment. J Clin Microbiol. 1995;33:352-355
32. Bestetti A, Presi S, Pierotti C, et al. Long-term virological effect of highly active antiretroviral therapy on cerebrospinal fluid and relationship with genotypic resistance. J Neurovirol. 2004;10(suppl 1):52-57 (Pubitemid 38325094)
33. Dunfee RL, Thomas ER, Wang J, et al. Loss of the N-linked glycosylation site at position 386 in the HIV envelope V4 region enhances macrophage tropism and is associated with dementia. Virology. 2007;367:222-234 (Pubitemid 47418935)
34. Thomas ER, Dunfee RL, Stanton J, et al. High frequency of defective vpu compared with tat and rev genes in brain from patients with HIV type 1 - associated dementia. Aids Res Hum Retrovirusues. 2007;23:575-580 (Pubitemid 46700893)
35. Mefford ME, Gorry PR, Kunstman K, Kolinsky SM, Gabuzda D. Bioinformatic prediction programs underestimate the frequency of CXCR4 usage by R5X4 HIV type 1 in brain and other tissues. Aids Res Hum Retroviruses. 2008;24:1215-1220
36. Gisslén M, Fuchs D, Svennerholm B, Hagberg L. Cerebrospinal fluid viral load, intrathecal immunoactivation, and cerebrospinal fluid monocytic cell count in HIV-1 infection. J Acquir Immune Defic Syndr. 1999;21:271-276 (Pubitemid 29357657)
37. Price RW, Epstein LG, Becker JT, et al. Biomarkers of HIV-1 CNS infection and injury. Neurology. 2007;69:1781-1788
38. Brew BJ, Letendre SL. Biomarkers of HIV related central nervous system disease. Int Rev Psychiatry. 2008;20:73-88. (Pubitemid 351196203)
39. Eden A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslen M. Immune activation of the central nervous system is still present after > 4 years of effective highly active antiretroviral therapy. J Infect Dis. 2007;196:1779-1783
40. Heaton RK, Velin RA, McCutchan. Neuropsychological impairment in human immunodeficiency virus infection: implications for employment. Psychosom Med. 1994;56:8-17.
41. Ellis RJ Moore DJ, Childers ME, Letendre S McCutchan JA Wolfson T. Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. Arch Neurol. 2002;59:923-928
42. Vitiello B, Goodkin K, Ashtana D, et al. HIV-1 RNA concentration and cognitive performance in a cohort of HIV positive people. AIDS. 2007;21:1415-1422 (Pubitemid 46988001)
43. Odiase FE, Ogunrin OA, Ogunniyi AA. Memory performance in HIV/Aids-a prospective case control study. Can J Neurol Sci. 2007;34:154-159 (Pubitemid 47000116)
44. Spudich S, Lollo N, Liegler T, Deeks SG, Price RW. Treatment benefit on cerebrospinal fluid HIV-1 levels in the setting of systemic virological suppression and failure. J Infect Dis. 2006;194:1686-1696 (Pubitemid 44901999)
45. Nath A, Sacktor N. Influence of highly active antiretroviral therapy on persistence of HIV in the central nervous system. Curr Opin Neurol. 2006;19:358-361 (Pubitemid 44246409)
46. Price RW, Spudich S. Antiretroviral therapy and central nervous system HIV type 1 infection. J Infect Dis. 2008;197:5294-5306 (Pubitemid 351717319)
47. Polis MA, Suzman DL, Yoder CP, et al. Suppression of cerebrospinal fluid HIV burden in antiretroviral naive patients on a potent four-drug antiretroviral regimen. AIDS. 2003;17:1167-1172
48. Mellgren A, Antinori A, Cinque P, et al. Cerebrospinal fluid HIV-1 infection usually responds well to antiretroviral treatment. Antivir Ther. 2005;10:701-707 (Pubitemid 41376848)
49. Yilmaz A, Svennerholm B, Hagberg L, Gisslén M. Cerebrospinal fluid viral loads reach less than 2 copies/mL in HIV-1-infected patients with effective antiretroviral therapy. Antivir Ther. 2006;11:833-837 (Pubitemid 44736174)
50. Eggers C, Hertogs K, Sturenburg HJ, van Lunzen J, Stellbrink HJ. Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with viral drug resistance or poor central nervous system drug penetration. AIDS. 2003;17:1897-1906 (Pubitemid 37070275)
51. Staprans S, Marlowe N, Glidden D, et al. Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection. AIDS. 1999;13:1051-1061 (Pubitemid 29361395)
52. Ellis RJ, Gamst AC, Capparelli E, et al. Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology. 2000;54:927-936 (Pubitemid 30111354)
53. Letendre SL, van den Brande G, Hermes A, et al. Lopinavir and ritonavir reduces the HIV RNA level in cerebrospinal fluid. Clin Infect Dis. 2007;45:1511-1517
54. Thomas SA. Anti-HIV drug distribution to the central nervous system. Curr Pharm Des. 2004;10:1313-1324 (Pubitemid 38568084)
55. Wynn HE, Brundage RC, Fletcher CV. Clinical implications of CNS penetration of antiretroviral drugs. CNS Drugs. 2002;16:595-609. (Pubitemid 34941127)
56. Letendre S, Macquie-Beck J, Capparelli E, et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008;65:65-70.
57. Cespedes MS, Aberg JA. Neuropyschiatric complications of antiretroviral therapy. Drug Saf. 2006;29:865-874
58. Clifford DB, Evans S, Yang Y, et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med. 2005;143:714-721 (Pubitemid 41693787)
59. Gutierrez F, Navarro A, Padilla, et al. Prediction of neuropsychiatric adverse events associated with long term efavirenz therapy using plasma drug level monitoring. Clin Infect Dis. 2005;41:1648-1653 (Pubitemid 41691605)
60. Fumaz CR, Munoz Moreno JA, Molto J, et al. Long term neuropsychiatric disorders on efavirenz based approaches: quality of life, psychological issues and adherences. J Acquir Immune Defic Syndr. 2005;38:560-565
61. Haas DW, Riboaudo HJ, Kim RB, et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adults Aids Clinical Trial Group Study. AIDS. 2004;18:2391-2400
62. Burger D, van der Heiden I, La Porte C, Koopmans P, 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;61:148-154 (Pubitemid 43382608)
63. Schweinsburg BC, Taylor MJ, Alhassoon OM, et al. Brain mitochondrial injury in human immunodeficiency virus-seropositive individuals taking nucleoside reverse trancriptase inhibitors. J Neurovirology. 2005;11:356-364
64. Ances B, Clifford DB. HIV associated neurocognitive disorders and the impact of combination antiretroviral therapy. Curr Neurol Neurosci Rep. 2008;8:455-461
65. Cohen RA, Boland R, Paul R. Neurocognitive performed enhanced by active antiretroviral therapy in HIV-infected women. AIDS. 2001;15:341-350 (Pubitemid 32163820)
66. Robertson KR, Robertson WT, Ford S, et al. Highly antitretroviral therapy improves neurocognitive functioning. J Acquir Immune Defic Syndr. 2004;36:562-566
67. Andersson LM, Hagberg L, Rosengren L. Normalisation of cerebrospinal fluid biomarkers paralles improvement of neurological following HAART in HIV dementia. A case report. BMC Infect Dis. 2006;2006:141.
68. Mehling M, Drechsler H Kuhle J, et al. Adaptation of antiretroviral therapy in human immunodeficiency virus infection with central nervous system involvement. J Neurovir. 2008;14:78-84. (Pubitemid 351314976)
69. Tozzi V, Balestra P, Bellagamba R, et al. Persistence of neuropsychological deficits during long term highly active antiretroviral therapy in patients with HIV related neurocognitive impairment: prevalence and risk factors. J Acquired Immune Defic Syndr. 2007;45:174-182 (Pubitemid 46869810)
70. Giancola ML, Lorenzini P, Balestra P, et al. Neuro active drugs do not influence neurocognitive performance in less advanced HIV-infected patients responding to highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2006;41:332-337
71. May S, Letendre S, Haubrich R, et al. Meeting practical challenging of a trial involving a multitude of treatment regimens: an example of a multi-center randomized controlled clinical trial in neuroAids. J Neuroimmune Pharmacol. 2007;2:97-104.
72. McGee B, Smith N, Aweeka F. HIV pharmacology: barriers to the eradication of HIV from the CNS. HIV Clin Trials. 2006;7:142-153 (Pubitemid 44309004)
73. Miller DS, Bauer B, Hartz AM. Modulation of p/glycoprotein at the blood brain barrier; opportunities to improve central nervous system pharmacotherapy. Pharmacol Rev. 2008;60;196-209. (Pubitemid 351962009)
74. Kingsley JD, Dou H, Morehead J, et al. Nanotechnology: a focus on nanoparticles as a drug delivery system. J Neuroimmune Pharmacol. 2006;1:340-350 (Pubitemid 44244138)
75. Spitzenberger TJ, Heilman D, Diekmann C, et al. Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis. J Cereb Blood Flow Metab. 2007;27:1033-1042 (Pubitemid 46659034)