The Chronicity of HIV Infection Should Drive the Research Strategy of NeuroHIV Treatment Studies: A Critical Review

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• 作者：Thomas M. Gates ; Lucette A. Cysique
• 刊名：CNS Drugs
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：30
• 期：1
• 页码：53-69
• 全文大小：803 KB
• 参考文献：1.Aichele S, Rabbitt P, Ghisletta P. Life span decrements in fluid intelligence and processing speed predict mortality risk. Psychol Aging. 2015;22:22.
  2.Cysique LA. Should longitudinal multisite studies become the new standard for investigating neurocognitive functions in HIV infection? Clin Infect Dis. 2015;60(3):481–2.
  3.McPhail ME, Robertson KR. Neurocognitive impact of antiretroviral treatment: thinking long-term. Curr HIV/AIDS Rep. 2011;8(4):249–56.PubMed CrossRef
  4.Ossenkoppele R, Jansen WJ, Rabinovici GD, et al. Prevalence of amyloid pet positivity in dementia syndromes: a meta-analysis. JAMA. 2015;313(19):1939–49.PubMed PubMedCentral CrossRef
  5.Jansen WJ, Ossenkoppele R, Knol DL, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313(19):1924–38.PubMed PubMedCentral CrossRef
  6.Brew BJ. Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. Aids. 2004;18(Suppl 1(18)):S75–8.
  7.Brew BJ, Crowe SM, Landay A, Cysique LA, Guillemin G. Neurodegeneration and ageing in the HAART era. J Neuroimmune Pharmacol. 2009;4(2):163–74.PubMed CrossRef
  8.Heaton RK, Temkin N, Dikmen S, Avitable N, Taylor MJ, Marcotte TD, et al. Detecting change: a comparison of three neuropsychological methods, using normal and clinical samples. Arch Clin Neuropsychol. 2001;16(1):75–91.PubMed CrossRef
  9.Gisslen M, Price RW, Nilsson S. The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence? (1471–2334 (Electronic)).
  10.Meyer AC, Boscardin WJ, Kwasa JK, Price RW. Is it time to rethink how neuropsychological tests are used to diagnose mild forms of HIV-associated neurocognitive disorders? Impact of false-positive rates on prevalence and power. (1423–0208 (Electronic)).
  11.Nightingale S, Winston A, Letendre S, Michael BD, McArthur JC, Khoo S, et al. Controversies in HIV-associated neurocognitive disorders. (1474–4465 (Electronic)).
  12.Holdnack JA, Xiaobin Z, Larrabee GJ, Millis SR, Salthouse TA. Confirmatory factor analysis of the WAIS-IV/WMS-IV. Assessment. 2011;18(2):178–91.PubMed PubMedCentral CrossRef
  13.Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69:1789–99.PubMed PubMedCentral CrossRef
  14.Su T, Schouten J, Geurtsen GJ, Wit FW, Stolte IG, Prins M, et al. Multivariate normative comparison, a novel method for more reliably detecting cognitive impairment in HIV infection. Aids. 2015;29(5):547–57.PubMed
  15.Woods SP, Rippeth JD, Frol AB, Levy JK, Ryan E, Soukup VM, et al. Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV. J Clin Exp Neuropsychol. 2004;26(6):759–78.PubMed CrossRef
  16.Strauss E, Sherman EMS, Spreen O. A compendium of neuropsychological tests: administration, norms, and commentary 3rd, editor. Oxford: Oxford University Press; 2006.
  17.Cysique LA, Heaton RK, Kamminga J, Lane T, Gates TM, Moore DM, et al. HIV-associated neurocognitive disorder in Australia: a case of a high-functioning and optimally treated cohort and implications for international neuroHIV research. J Neurovirol. 2014;20(3):258–68.PubMed PubMedCentral CrossRef
  18.Gupta S, Vaida F, Riggs K, Jin H, Grant I, Cysique L, et al. Neuropsychological performance in mainland china: the effect of urban/rural residence and self-reported daily academic skill use. J Int Neuropsychol Soc. 2011;17(1):163–73.PubMed PubMedCentral CrossRef
  19.Shuttleworth-Edwards AB, Kemp RD, Rust AL, Muirhead JG, Hartman NP, Radloff SE. Cross-cultural effects on IQ test performance: a review and preliminary normative indications on WAIS-III test performance. J Clin Exp Neuropsychol. 2004;26(7):903–20.PubMed CrossRef
  20.Nunnally J, Bernstein I. Psychometric theory. 3rd ed. New York: McGraw-Hill; 1994.
  21.Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75:2087–96.PubMed PubMedCentral CrossRef
  22.Heaton RK, Miller SW, Taylor MJ, Grant I. Revised comprehensive norms for an expanded Halstead-Reitan Battery: demographically adjusted neuropsychological norms for African American and Caucasian adults scoring program. Odessa: Psychological Assessment Resources; 2004.
  23.Taylor MJ, Heaton RK. Sensitivity and specificity of WAIS-III/WMS-III demographically corrected factor scores in neuropsychological assessment. J Int Neuropsychol Soc. 2001;7(7):867–74.PubMed
  24.Grant I, Franklin DJ, Deutsch R, Woods SP, Vaida F, Ellis RJ, et al. Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology. 2014;10:2055–62.CrossRef
  25.Rourke S, Rachlis A, Gill J, Power C, Kovacs C, Brunetta J, et al. Relative risk and factors associated with progression to symptomatic HAND. Seattle: CROI; 2015.
  26.Sacktor N, Skolasky R, Seaberg E, Munro C, Becker J, Martin E, et al. Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study. Neurology. 2015 (In Press).
  27.Sacktor N, Robertson K. Evolving clinical phenotypes in HIV-associated neurocognitive disorders. Curr Opin HIV AIDS. 2014;9(6):517–20.PubMed PubMedCentral CrossRef
  28.Cysique L, Maruff P, Brew B. Prevalence and pattern of neuropsychological impairment in HIV/AIDS-infection across pre and post-highly active antiretroviral therapy eras: a combined study of 2 cohorts. J Neurovirol. 2004;10:350–7.PubMed CrossRef
  29.Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2010;17(1):3–16.PubMed PubMedCentral CrossRef
  30.Blackstone K, Moore DJ, Heaton RK, Franklin DR Jr, Woods SP, Clifford DB, et al. Diagnosing symptomatic HIV-associated neurocognitive disorders: self-report versus performance-based assessment of everyday functioning. J Int Neuropsychol Soc. 2012;18(1):79–88.PubMed CrossRef
  31.APA. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychological Association; 1994.
  32.Weintraub S, Wicklund AH, Salmon DP. The neuropsychological profile of Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(4):a006171.PubMed PubMedCentral CrossRef
  33.Cysique LA, Hewitt T, Croitoru-Lamoury J, Taddei K, Martins RN, Chew CS, et al. APOE epsilon4 moderates abnormal CSF-abeta-42 levels, while neurocognitive impairment is associated with abnormal CSF tau levels in HIV+ individuals—a cross-sectional observational study. BMC Neurol. 2015;15(51):51.PubMed PubMedCentral CrossRef
  34.Soontornniyomkij V, Moore DJ, Gouaux B, Soontornniyomkij B, Tatro ET, Umlauf A, et al. Cerebral beta-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE epsilon4 carriers. Aids. 2012;26(18):2327–35.PubMed PubMedCentral CrossRef
  35.Ernst T, Chang L, Jovicich J, Ames N, Arnold S. Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology. 2002;59(9):1343–9.PubMed CrossRef
  36.Byrd DA, Fellows RP, Morgello S, Franklin D, Heaton RK, Deutsch R, et al. Neurocognitive impact of substance use in HIV infection. J Acquir Immune Defic Syndr. 2011;58(2):154–62.PubMed PubMedCentral CrossRef
  37.Clifford DB, Vaida F, Kao YT, Franklin DR, Letendre SL, Collier AC, et al. Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people. Neurology. 2015;84(3):241–50.PubMed PubMedCentral CrossRef
  38.Cysique LA, Dermody N, Carr A, Brew BJ, Teesson M. The role of depression chronicity and recurrence on neurocognitive dysfunctions in HIV-infected adults. J Neurovirol. 2015 [Epub ahead of print].
  39.Heaton RK, Franklin DR Jr, Deutsch R, Letendre S, Ellis RJ, Casaletto K, et al. Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. Clin Infect Dis. 2015;60(3):473–80.PubMed CrossRef PubMedCentral
  40.Cherner M, Letendre S, Heaton RK, Durelle J, Marquie-Beck J, Gragg B, et al. Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology. 2005;64(8):1343–7.PubMed CrossRef
  41.Chan HM, Stolwyk R, Neath J, Kelso W, Walterfang M, Mocellin R, et al. Neurocognitive similarities between severe chronic schizophrenia and behavioural variant frontotemporal dementia. Psychiatry Res. 2015;225(3):658–66.PubMed CrossRef
  42.Nakasujja N, Allebeck P, Agren H, Musisi S, Katabira E. Cognitive dysfunction among HIV positive and HIV negative patients with psychosis in Uganda. PLoS One. 2012;7(9):e44415.PubMed PubMedCentral CrossRef
  43.Cysique LA, Maruff P, Brew BJ. Variable benefit in neuropsychological function in HIV-infected HAART-treated patients. Neurology. 2006;66:1447–50.PubMed CrossRef
  44.Zhao W. A better alternative to stratified permuted block design for subject randomization in clinical trials. Stat Med. 2014;33(30):5239–48.PubMed PubMedCentral CrossRef
  45.American Academy of Neurology, Dana Consortium. Clinical confirmation of the American Academy of Neurology algorithm for HIV-1-associated cognitive/motor disorder (Dana Consortium on therapy for HIV dementia and related cognitive disorders). Neurology. 1996;47:1247–53.CrossRef
  46.Janssen R, Comblath D, Hopkins J, Epstein LG, Foa RP, McArthur JC, et al. Nomenclature and research case definitions for neurologic manifestations immunodeficiency virus type-1 (HIV-1): reports of a Working group of the American Academy of Neurology AIDS Task Force. Neurology. 1991;41:778–85.CrossRef
  47.Price RW, Brew BJ. The AIDS dementia complex. J Infect Dis. 1988;158:1079–83.PubMed CrossRef
  48.Rosenberg RN. Defining amyloid pathology in persons with and without dementia syndromes: making the right diagnosis. JAMA. 2015;313(19):1913–4.PubMed CrossRef
  49.Hopcroft L, Bester L, Clement D, Quigley A, Sachdeva M, Rourke SB, et al. “My body’s a 50 year-old but my brain is definitely an 85 year-old”: exploring the experiences of men ageing with HIV-associated neurocognitive challenges. J Int AIDS Soc. 2013;16(18506):18506.PubMed PubMedCentral
  50.Thames AD, Becker BW, Marcotte TD, Hines LJ, Foley JM, Ramezani A, et al. Depression, cognition, and self-appraisal of functional abilities in HIV: an examination of subjective appraisal versus objective performance. Clin Neuropsychol. 2011;25(2):224–43.PubMed PubMedCentral CrossRef
  51.Garand L, Lingler JH, Conner KO, Dew MA. Diagnostic labels, stigma, and participation in research related to dementia and mild cognitive impairment. Res Gerontol Nurs. 2009;2(2):112–21.PubMed PubMedCentral CrossRef
  52.Courtney DL. Dealing with mild cognitive impairment: help for patients and caregivers. Clin Geriatr Med. 2013;29(4):895–905.PubMed CrossRef
  53.Blackstone K, Tobin A, Posada C, Gouaux B, Grant I, Moore DJ, et al. HIV-infected persons with bipolar disorder are less aware of memory deficits than HIV-infected persons without bipolar disorder. J Clin Exp Neuropsychol. 2012;34(7):773–81.PubMed PubMedCentral CrossRef
  54.Rueda S, Law S, Rourke SB. Psychosocial, mental health, and behavioral issues of aging with HIV. Curr Opin HIV AIDS. 2014;9(4):325–31.PubMed CrossRef
  55.Wright EJ. The Four Seasons approach to the management of modern HIV medicine in high-income countries. Sex Health. 2012;9(5):491–2.PubMed CrossRef
  56.Barnett JH, Lewis L, Blackwell AD, Taylor M. Early intervention in Alzheimer’s disease: a health economic study of the effects of diagnostic timing. BMC Neurol. 2014;14(101):101.PubMed PubMedCentral CrossRef
  57.Molsberry SA, Lecci F, Kingsley L, Junker B, Reynolds S, Goodkin K, et al. Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study. Aids. 2015;29(6):713–21.PubMed CrossRef
  58.Carey CL, Woods SP, Gonzalez R, Conover E, Marcotte TD, Grant I, et al. Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol. 2004;26(3):307–19.PubMed CrossRef
  59.Blackstone K, Moore DJ, Franklin DR, Clifford DB, Collier AC, Marra CM, et al. Defining neurocognitive impairment in HIV: deficit scores versus clinical ratings. Clin Neuropsychol. 2012;26(6):894–908.PubMed CrossRef
  60.Kramer-Hammerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R. Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res. 2005;111(2):194–213.PubMed CrossRef
  61.Buescher JL, Gross S, Gendelman HE, Ikezu T. The neuropathogenesis of HIV-1 infection. Handb Clin Neurol. 2007;85:45–67.PubMed CrossRef
  62.Valcour VG, Ananworanich J, Agsalda M, Sailasuta N, Chalermchai T, Schuetz A, et al. HIV DNA reservoir increases risk for cognitive disorders in cART-naive patients. PLoS One. 2013;8(7):e70164.PubMed PubMedCentral CrossRef
  63.Cysique LA, Hey-Cunningham WJ, Dermody N, Chan P, Brew BJ, Koelsch K.K. Peripheral blood mononuclear cells HIV DNA levels impact intermittently on neurocognition. PLoS One. 2015;10(4):e0120488.
  64.Ferretti F, Gisslen M, Cinque P, Price RW. Cerebrospinal fluid HIV escape from antiretroviral therapy. Curr HIV/AIDS Rep. 2015;12(2):280–8.PubMed CrossRef
  65.Vazquez-Santiago F, Garcia Y, Rivera-Roman I, Noel RJ Jr, Wojna V, Melendez LM, et al. Longitudinal analysis of cerebrospinal fluid and plasma HIV-1 envelope sequences isolated from a single donor with HIV asymptomatic neurocognitive impairment. J Virol Antivir Res. 2015;4(1):2324–8955.CrossRef
  66.Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis. 2010;50(5):773–8.PubMed CrossRef
  67.Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, et al. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS. 2007;21(14):1915–21.PubMed CrossRef
  68.Cysique LA, Moffat K, Moore DM, Lane TA, Davies NW, Carr A, et al. HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study. PLoS One. 2013;8(4):e61738.PubMed PubMedCentral CrossRef
  69.Gongvatana A, Harezlak J, Buchthal S, Daar E, Schifitto G, Campbell T, et al. Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J Neurovirol. 2013;19(3):209–18.PubMed PubMedCentral CrossRef
  70.Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, et al. Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS. 2011;25(5):625–33.PubMed PubMedCentral CrossRef
  71.Dahl V, Peterson J, Fuchs D, Gisslen M, Palmer S, Price RW. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS. 2014;28(15):2251–8.PubMed PubMedCentral CrossRef
  72.Decloedt EH, Rosenkranz B, Maartens G, Joska J. Central nervous system penetration of antiretroviral drugs: pharmacokinetic, pharmacodynamic and pharmacogenomic considerations. Clin Pharmacokinet. 2015;17:17.
  73.Louboutin JP, Agrawal L, Reyes BA, Van Bockstaele EJ, Strayer DS. HIV-1 gp120-induced injury to the blood
  ain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stress. J Neuropathol Exp Neurol. 2010;69(8):801–16.PubMed PubMedCentral CrossRef
  74.Mishra R, Singh SK. HIV-1 Tat C phosphorylates VE-cadherin complex and increases human brain microvascular endothelial cell permeability. BMC neuroscience. 2014;15:80.PubMed PubMedCentral CrossRef
  75.Bumpus N, Ma Q, Moore DJ, Best BM, Ellis RJ, Achim CL, et al. Antiretroviral concentrations in brain tissue are similar to or exceed those in CSF. Seattle: CROI; 2015.
  76.Letendre S. Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Top Antivir Med. 2011;19(4):137–42.PubMed PubMedCentral
  77.Cysique LA, Brew BJ. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev. 2009;19(2):169–85.PubMed CrossRef
  78.Cysique LA, Waters EK, Brew BJ. Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research. BMC Neurol. 2011;11:148.PubMed PubMedCentral CrossRef
  79.Baker LM, Paul RH, Heaps-Woodruff JM, Chang JY, Ortega M, Margolin Z, et al. The effect of central nervous system penetration effectiveness of highly active antiretroviral therapy on neuropsychological performance and neuroimaging in HIV infected individuals. J Neuroimmune Pharmacol. 2015;22:22.
  80.Wilson MJ, Martin-Engel L, Vassileva J, Gonzalez R, Martin EM. An investigation of the effects of antiretroviral central nervous system penetration effectiveness on procedural learning in HIV+ drug users. J Clin Exp Neuropsychol. 2013;35(9):915–25.PubMed CrossRef
  81.Casado JL, Marin A, Moreno A, Iglesias V, Perez-Elias MJ, Moreno S, et al. Central nervous system antiretroviral penetration and cognitive functioning in largely pretreated HIV-infected patients. J Neurovirol. 2014;20(1):54–61.PubMed CrossRef
  82.Smurzynski M, Wu K, Letendre S, Robertson K, Bosch RJ, Clifford DB, et al. Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort. Aids. 2011;25(3):357–65.PubMed PubMedCentral CrossRef
  83.Vassallo M, Durant J, Biscay V, Lebrun-Frenay C, Dunais B, Laffon M, et al. Can high central nervous system penetrating antiretroviral regimens protect against the onset of HIV-associated neurocognitive disorders? Aids. 2014;28(4):493–501.PubMed CrossRef
  84.Cusini A, Vernazza PL, Yerly S, Decosterd LA, Ledergerber B, Fux CA, et al. Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid. J Acquir Immune Defic Syndr. 2013;62(1):28–35.PubMed CrossRef
  85.Caniglia EC, Cain LE, Justice A, Tate J, Logan R, Sabin C, et al. Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions. Neurology. 2014;83(2):134–41.PubMed PubMedCentral CrossRef
  86.Garvey L, Winston A, Walsh J, Post F, Porter K, Gazzard B, et al. Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease. Neurology. 2011;76(8):693–700.PubMed PubMedCentral CrossRef
  87.Dunn D, Babiker A, Hooker M, Darbyshire J. The dangers of inferring treatment effects from observational data: a case study in HIV infection. Control Clin Trials. 2002;23(2):106–10.PubMed CrossRef
  88.Berger JR, Clifford DB. The relationship of CPE to HIV dementia: slain by an ugly fact? Neurology. 2014;83(2):109–10.PubMed CrossRef
  89.McLauchlan D, Robertson NP. Reducing central nervous system complications associated with the human immunodeficiency virus. J Neurol. 2014;261(9):1842–5.PubMed CrossRef
  90.Beardsley J, Le T. Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions. Neurology. 2015;84(6):632.PubMed CrossRef
  91.Enting RH, Hoetelmans RM, Lange JM, Burger DM, Beijnen JH, Portegies P. Antiretroviral drugs and the central nervous system. Aids. 1998;12(15):1941–55.PubMed CrossRef
  92.Cysique LA, Maruff P, Brew BJ. Antiretroviral therapy in HIV infection: are neurologically active drugs important? Arch Neurol. 2004;61(11):1699–704.PubMed CrossRef
  93.Bunupuradah T, Chetchotisakd P, Jirajariyavej S, Valcour V, Bowonwattanuwong C, Munsakul W, et al. Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy. J Neurovirol. 2012;18(6):479–87.PubMed CrossRef
  94.Sacktor N, Nakasujja N, Skolasky R, Robertson K, Wong M, Musisi S, et al. Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa. Neurology. 2006;67(2):311–4.PubMed CrossRef
  95.Valcour VG, Shiramizu BT, Sithinamsuwan P, Nidhinandana S, Ratto-Kim S, Ananworanich J, et al. HIV DNA and cognition in a Thai longitudinal HAART initiation cohort: the SEARCH 001 Cohort Study. Neurology. 2009;72(11):992–8.PubMed PubMedCentral CrossRef
  96.Joseph J, Achim CL, Boivin MJ, Brew BJ, Clifford DB, Colosi DA, et al. Global NeuroAIDS roundtable. J Neurovirol. 2013;19(1):1–9.PubMed PubMedCentral CrossRef
  97.Ellis RJ, Letendre S, Vaida F, Haubrich R, Heaton RK, Sacktor N, et al. Randomized trial of central nervous system-targeted antiretrovirals for HIV-associated neurocognitive disorder. Clin Infect Dis. 2014;58(7):1015–22.PubMed PubMedCentral CrossRef
  98.Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, et al. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology. 2009;73(5):342–8.PubMed PubMedCentral CrossRef
  99.Marra CM. HIV-associated neurocognitive disorders and central nervous system drug penetration: what next? Antivir Ther. 2015;20(4):365–7.PubMed CrossRef
  100.Fabbiani M, Grima P, Milanini B, Mondi A, Baldonero E, Ciccarelli N, et al. Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility. Antivir Ther. 2015;20(4):441–7.PubMed CrossRef
  101.Underwood J, Robertson KR, Winston A. Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease? Aids. 2015;29(3):253–61.PubMed CrossRef
  102.Zhang F, Heaton RK, Wu H, Jin H, Zhao H, Yu X, et al., editors. Randomized clinical trial of antiretroviral therapy for prevention of HAND. Seattle: CROI 2015; 2015. http://​www.​croiconference.​org/​sessions/​randomized-clinical-trial-antiretroviral-therapy-prevention-hand .
  103.Spudich SS, Ances BM. CROI 2015: neurologic complications of HIV infection. Top Antivir Med. 2015;23(1):47–55.PubMed
  104.Munoz-Moreno JA, Fumaz CR, Ferrer MJ, Gonzalez-Garcia M, Molto J, Negredo E, et al. Neuropsychiatric symptoms associated with efavirenz: prevalence, correlates, and management. A neurobehavioral review. AIDS Rev. 2009;11(2):103–9.PubMed
  105.Decloedt EH, Maartens G. Neuronal toxicity of efavirenz: a systematic review. Expert Opin Drug Saf. 2013;12(6):841–6.PubMed CrossRef
  106.Winston A, Puls R, Kerr SJ, Duncombe C, Li PC, Gill JM, et al. Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: a randomized, controlled study. HIV Med. 2012;13(4):245–51.PubMed
  107.Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, et al. Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study. Clin Infect Dis. 2010;51(7):855–64.PubMed CrossRef
  108.Cysique LA, Franklin D Jr, Abramson I, Ellis RJ, Letendre S, Collier A, et al. Normative data and validation of a regression based summary score for assessing meaningful neuropsychological change. J Clin Exp Neuropsychol. 2011;33(5):505–22.PubMed PubMedCentral CrossRef
  109.Brown LA, Jin J, Ferrell D, Sadic E, Obregon D, Smith AJ, et al. Efavirenz promotes beta-secretase expression and increased Abeta1-40,42 via oxidative stress and reduced microglial phagocytosis: implications for HIV associated neurocognitive disorders (HAND). PLoS One. 2014;9(4):e95500.PubMed PubMedCentral CrossRef
  110.Kelly KM, Beck SE, Metcalf Pate KA, Queen SE, Dorsey JL, Adams RJ, et al. Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain. Aids. 2013;27(18):F21–8.PubMed PubMedCentral CrossRef
  111.Melica G, Canestri A, Peytavin G, Lelievre JD, Bouvier-Alias M, Clavel C, et al. Maraviroc-containing regimen suppresses HIV replication in the cerebrospinal fluid of patients with neurological symptoms. Aids. 2010;24(13):2130–3.PubMed CrossRef
  112.Tiraboschi JM, Niubo J, Curto J, Podzamczer D. Maraviroc concentrations in cerebrospinal fluid in HIV-infected patients. J Acquir Immune Defic Syndr. 2010;55(5):606–9.PubMed CrossRef
  113.Yilmaz A, Watson V, Else L, Gisslen M. Cerebrospinal fluid maraviroc concentrations in HIV-1 infected patients. Aids. 2009;23(18):2537–40.PubMed CrossRef
  114.Ndhlovu LC, Umaki T, Chew GM, Chow DC, Agsalda M, Kallianpur KJ, et al. Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND). J Neurovirol. 2014;20(6):571–82.PubMed PubMedCentral CrossRef
  115.Gates TM, Cysique LA, Chaganti J, Siefried KJ, Brew BJ, editors. Maraviroc-enhanced CART improves cognition in virally suppressed HAND: a pilot study. Seattle: CROI 2015; 2015. http://​www.​croiconference.​org/​sessions/​maraviroc-enhanced-cart-improves-cognition-virally-suppressed-hand-pilot-study .
  116.Perez Valero I, Gonzalez-Baeza A, Montes Ramirez ML. Central nervous system penetration and effectiveness of darunavir/ritonavir monotherapy. AIDS Rev. 2014;16(2):101–8.
  117.Perez-Valero I, Gonzalez-Baeza A, Estebanez M, Montes-Ramirez ML, Bayon C, Pulido F, et al. Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy. PLoS One. 2013;8(7):e69493.PubMed PubMedCentral CrossRef
  118.Santos JR, Munoz-Moreno JA, Molto J, Prats A, Curran A, Domingo P, et al. Virological efficacy in cerebrospinal fluid and neurocognitive status in patients with long-term monotherapy based on lopinavir/ritonavir: an exploratory study. PLoS One. 2013;8(7):e70201.PubMed PubMedCentral CrossRef
  119.Letendre SL. Editorial commentary: protease inhibitor monotherapy: safe for the CNS in durably suppressed patients? Clin Infect Dis. 2014;59(11):1635–7.PubMed PubMedCentral CrossRef
  120.Perez-Valero I, Gonzalez-Baeza A, Estebanez M, Monge S, Montes-Ramirez ML, Bayon C, et al. A prospective cohort study of neurocognitive function in aviremic HIV-infected patients treated with 1 or 3 antiretrovirals. Clin Infect Dis. 2014;59(11):1627–34.PubMed PubMedCentral CrossRef
  121.Caramatti G, Ferretti F, Di Biagio A, Capetti A, Antinori A, Sora F, et al., editors. Similar neurocognitive performance in patients on ATV/r monotherapy vs triple therapy. Seattle: CROI 2015; 2015. http://​www.​croiconference.​org/​sessions/​similar-neurocognitive-performance-patients-atvr-monotherapy-vs-triple-therapy .
  122.Croteau D, Letendre S, Best BM, Ellis RJ, Breidinger S, Clifford D, et al. Total raltegravir concentrations in cerebrospinal fluid exceed the 50-percent inhibitory concentration for wild-type HIV-1. Antimicrob Agents Chemother. 2010;54(12):5156–60.PubMed PubMedCentral CrossRef
  123.Yilmaz A, Gisslen M, Spudich S, Lee E, Jayewardene A, Aweeka F, et al. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection. PLoS One. 2009;4(9):e6877.PubMed PubMedCentral CrossRef
  124.Calcagno A, Simiele M, Alberione MC, Bracchi M, Marinaro L, Ecclesia S, et al. Cerebrospinal fluid inhibitory quotients of antiretroviral drugs in HIV-infected patients are associated with compartmental viral control. Clin Infect Dis. 2015;60(2):311–7.PubMed CrossRef
  125.Letendre SL, Mills AM, Tashima KT, Thomas DA, Min SS, Chen S, et al. ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects. Clin Infect Dis. 2014;59(7):1032–7.PubMed PubMedCentral CrossRef
  126.National Institute of Health News Releases. Starting antiretroviral treatment early improves outcomes for HIV-infected individuals. NIH-Funded Trial Results Likely Will Impact Global Treatment Guidelines http://​www.​niaid.​nih.​gov/​news/​newsreleases/​2015/​Pages/​START.​aspx2015 [cited 2015 27th of May].
  127.The INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;20:20.
  128.Garvey L, Nelson M, Latch N, Erlwein OW, Allsop JM, Mitchell A, et al. CNS effects of a CCR5 inhibitor in HIV-infected subjects: a pharmacokinetic and cerebral metabolite study. J Antimicrob Chemother. 2012;67(1):206–12.PubMed CrossRef
  129.Young AC, Yiannoutsos CT, Hegde M, Lee E, Peterson J, Walter R, et al. Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Neurology. 2014;83(18):1592–600.PubMed PubMedCentral CrossRef
  130.Schweinsburg BC, Taylor MJ, Alhassoon OM, Gonzalez R, Brown GG, Ellis RJ, et al. Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol. 2005;11(4):356–64.PubMed CrossRef
  131.Winston A, Duncombe C, Li PC, Gill JM, Kerr SJ, Puls RL, et al. Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy. Neuroradiology. 2012;54(12):1331–9.PubMed CrossRef
  132.Rae CD. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res. 2014;39(1):1–36.PubMed CrossRef
  133.Sailasuta N, Ananworanich J, Lerdlum S, Sithinamsuwan P, Fletcher JL, Tipsuk S, Pothisri M, et al. Neuronal-glia markers by magnetic resonance spectroscopy in HIV before and after combination antiretroviral therapy. (1944–7884 (Electronic)).
  
• 作者单位：Thomas M. Gates (1) (2)
  Lucette A. Cysique (3) (4)
  
  1. St. Vincent’s Hospital Department of Neurology, Sydney, Australia
  2. St. Vincent’s Hospital Centre for Applied Medical Research, Sydney, Australia
  3. Neuroscience Research Australia, 139 Barker Street, Randwick, PO Box 1165, Sydney, NSW, 2031, Australia
  4. The University of New South Wales, Sydney, Australia
  
• 刊物主题：Neurology; Psychopharmacology; Pharmacotherapy; Neurosciences; Psychiatry;
• 出版者：Springer International Publishing
• ISSN：1179-1934

文摘

HIV infection has become a chronic illness when successfully treated with combined antiretroviral therapy (cART). The long-term health prognosis of aging with controlled HIV infection and HIV-associated neurocognitive disorder (HAND) remains unclear. In this review, we propose that, almost 20 years after the introduction of cART, a change in research focus is needed, with a greater emphasis on chronicity effects driving our research strategy. We argue that pre-emptive documentation of episodes of mild neurocognitive dysfunction is needed to determine their long-term prognosis. This strategy would also seek to optimally represent the entire HAND spectrum in therapeutic trials to assess positive and/or negative treatment effects on brain functions. In the first part of the paper, to improve the standard implementation of the Frascati HAND diagnostic criteria, we provide a brief review of relevant quantitative neuropsychology concepts to clarify their appropriate application for a non-neuropsychological audience working in HIV research and wanting to conduct randomized clinical trials on brain functions. The second part comprises a review of various antiretroviral drug classes and individual agents with respect to their effects on HAND, while also addressing the question of when cART should be initiated to potentially reduce HAND incidence. In each section, we use recent observational studies and randomized controlled trials to illustrate our perspective while also providing relevant statistical comments. We conclude with a discussion of the neuroimaging methods that could be combined with neuropsychological approaches to enhance the validity of HIV neurology (neuroHIV) treatment effect studies.