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Semin Neurol 2014; 34(01): 014-020
DOI: 10.1055/s-0034-1372338
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of HIV in the Central Nervous System

Aylin Yilmaz
1   Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden
,
Magnus Gisslén
1   Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
08. April 2014 (online)

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Abstract

Central nervous system (CNS) infection is an important part of systemic human immunodeficiency disease (HIV) infection. It is most often asymptomatic, but can sometimes lead to severe neurologic disease, particularly in advanced stages of immunosuppression. CNS HIV infection usually responds well to antiretroviral treatment, but there are concerns that treatment may not always be fully effective in treating or preventing milder CNS disease and that it, under certain circumstances, might be important to consider antiretroviral drug distribution and effects within the CNS.

Keywords

human immunodeficiency disease - antiretroviral treatment - central nervous system
 

  • References

  • 1 Davis LE, Hjelle BL, Miller VE , et al. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology 1992; 42 (9) 1736-1739
    CrossrefPubMedGoogle Scholar
  • 2 Spudich S, Gisslen M, Hagberg L , et al. Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden. J Infect Dis 2011; 204 (5) 753-760
    CrossrefPubMedGoogle Scholar
  • 3 Valcour V, Chalermchai T, Sailasuta N , et al; RV254/SEARCH 010 Study Group. Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis 2012; 206 (2) 275-282
    CrossrefPubMedGoogle Scholar
  • 4 Conrad AJ, Schmid P, Syndulko K , et al. Quantifying HIV-1 RNA using the polymerase chain reaction on cerebrospinal fluid and serum of seropositive individuals with and without neurologic abnormalities. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 10 (4) 425-435
    CrossrefPubMedGoogle Scholar
  • 5 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 (4) 271-276
    CrossrefPubMedGoogle Scholar
  • 6 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
    CrossrefPubMedGoogle Scholar
  • 7 Price RW, Brew BJ. The AIDS dementia complex. J Infect Dis 1988; 158 (5) 1079-1083
    CrossrefPubMedGoogle Scholar
  • 8 Portegies P, de Gans J, Lange JM , et al. Declining incidence of AIDS dementia complex after introduction of zidovudine treatment. BMJ 1989; 299 (6703) 819-821
    CrossrefPubMedGoogle Scholar
  • 9 Brew BJ, Rosenblum M, Price RW. AIDS dementia complex and primary HIV brain infection. J Neuroimmunol 1988; 20 (2-3) 133-140
    CrossrefPubMedGoogle Scholar
  • 10 Heaton RK, Clifford DB, Franklin Jr DR , et al; CHARTER Group. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75 (23) 2087-2096
    CrossrefPubMedGoogle Scholar
  • 11 Heaton RK, Franklin DR, Ellis RJ , et al; CHARTER Group; HNRC Group. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 2011; 17 (1) 3-16
    CrossrefPubMedGoogle Scholar
  • 12 Sinclair E, Ronquillo R, Lollo N , et al. Antiretroviral treatment effect on immune activation reduces cerebrospinal fluid HIV-1 infection. J Acquir Immune Defic Syndr 2008; 47 (5) 544-552
    CrossrefPubMedGoogle Scholar
  • 13 Yilmaz A, Price RW, Gisslén M. Antiretroviral drug treatment of CNS HIV-1 infection. J Antimicrob Chemother 2012; 67 (2) 299-311
    CrossrefPubMedGoogle Scholar
  • 14 Engelhardt B, Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 2009; 31 (4) 497-511
    CrossrefPubMedGoogle Scholar
  • 15 Chiodi F, Keys B, Albert J , et al. Human immunodeficiency virus type 1 is present in the cerebrospinal fluid of a majority of infected individuals. J Clin Microbiol 1992; 30 (7) 1768-1771
    PubMedGoogle Scholar
  • 16 Schnell G, Spudich S, Harrington P, Price RW, Swanstrom R. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia. PLoS Pathog 2009; 5 (4) e1000395
    CrossrefPubMedGoogle Scholar
  • 17 Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. J Virol 2010; 84 (5) 2395-2407
    CrossrefPubMedGoogle Scholar
  • 18 Hazenberg MD, Otto SA, Wit FW, Lange JM, Hamann D, Miedema F. Discordant responses during antiretroviral therapy: role of immune activation and T cell redistribution rather than true CD4 T cell loss. AIDS 2002; 16 (9) 1287-1289
    CrossrefPubMedGoogle Scholar
  • 19 Ransohoff RM, Kivisäkk P, Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 2003; 3 (7) 569-581
    CrossrefPubMedGoogle Scholar
  • 20 Smit TK, Brew BJ, Tourtellotte W, Morgello S, Gelman BB, Saksena NK. Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment. J Virol 2004; 78 (18) 10133-10148
    CrossrefPubMedGoogle Scholar
  • 21 Cysique LA, Maruff P, Brew BJ. Variable benefit in neuropsychological function in HIV-infected HAART-treated patients. Neurology 2006; 66 (9) 1447-1450
    CrossrefPubMedGoogle Scholar
  • 22 Ellis RJ, Badiee J, Vaida F , et al; CHARTER Group. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS 2011; 25 (14) 1747-1751
    CrossrefPubMedGoogle Scholar
  • 23 Abdulle S, Mellgren A, Brew BJ , et al. CSF neurofilament protein (NFL) — a marker of active HIV-related neurodegeneration. J Neurol 2007; 254 (8) 1026-1032
    CrossrefPubMedGoogle Scholar
  • 24 Crum-Cianflone NF, Moore DJ, Letendre S , et al. Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons. Neurology 2013; 80 (4) 371-379
    CrossrefPubMedGoogle Scholar
  • 25 Sailasuta N, Ross W, Ananworanich J , et al; RV254/SEARCH 010 protocol teams. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PLoS ONE 2012; 7 (11) e49272
    CrossrefPubMedGoogle Scholar
  • 26 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) 529-536
    PubMedGoogle Scholar
  • 27 Edén A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslén 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 (12) 1779-1783
    CrossrefPubMedGoogle Scholar
  • 28 Harezlak J, Buchthal S, Taylor M , et al; HIV Neuroimaging Consortium. Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 2011; 25 (5) 625-633
    CrossrefPubMedGoogle Scholar
  • 29 Yilmaz A, Yiannoutsos CT, Fuchs D , et al. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy. J Neuroinflammation 2013; 10: 62
    CrossrefPubMedGoogle Scholar
  • 30 Takasawa K, Terasaki T, Suzuki H, Ooie T, Sugiyama Y. Distributed model analysis of 3′-azido-3′-deoxythymidine and 2′,3′-dideoxyinosine distribution in brain tissue and cerebrospinal fluid. J Pharmacol Exp Ther 1997; 282 (3) 1509-1517
    PubMedGoogle Scholar
  • 31 Best BM, Letendre SL, Koopmans P , et al; CHARTER Study Group. Low cerebrospinal fluid concentrations of the nucleotide HIV reverse transcriptase inhibitor, tenofovir. J Acquir Immune Defic Syndr 2012; 59 (4) 376-381
    CrossrefPubMedGoogle Scholar
  • 32 Foudraine NA, Hoetelmans RM, Lange JM , et al. Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine. Lancet 1998; 351 (9115) 1547-1551
    CrossrefPubMedGoogle Scholar
  • 33 Best BM, Koopmans PP, Letendre SL , et al; CHARTER Group. Efavirenz concentrations in CSF exceed IC50 for wild-type HIV. J Antimicrob Chemother 2011; 66 (2) 354-357
    CrossrefPubMedGoogle Scholar
  • 34 van Praag RM, van Weert EC, van Heeswijk RP , et al. Stable concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid during 2 years of therapy. Antimicrob Agents Chemother 2002; 46 (3) 896-899
    CrossrefPubMedGoogle Scholar
  • 35 Nguyen A, Rossi S, Croteau D , et al; CHARTER Group. Etravirine in CSF is highly protein bound. J Antimicrob Chemother 2013; 68 (5) 1161-1168
    CrossrefPubMedGoogle Scholar
  • 36 Mora-Peris B, Watson V, Vera J , et al. Rilpivirine concentrations in plasma and cerebrospinal fluid after switching from nevirapine-containing cART. Paper presented at: 14th International Workshop on Clinical Pharmacology of HIV Therapy; April 22–24, 2013; Amsterdam, the Netherlands
    PubMedGoogle Scholar
  • 37 Kim RB, Fromm MF, Wandel C , et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998; 101 (2) 289-294
    CrossrefPubMedGoogle Scholar
  • 38 Vernazza P, Daneel S, Schiffer V , et al. The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial. AIDS 2007; 21 (10) 1309-1315
    CrossrefPubMedGoogle Scholar
  • 39 Katlama C, Valantin MA, Algarte-Genin M , et al. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS 2010; 24 (15) 2365-2374
    PubMedGoogle Scholar
  • 40 Meynard JL, Bouteloup V, Landman R , et al; KALESOLO Study Group. Lopinavir/ritonavir monotherapy versus current treatment continuation for maintenance therapy of HIV-1 infection: the KALESOLO trial. J Antimicrob Chemother 2010; 65 (11) 2436-2444
    CrossrefPubMedGoogle Scholar
  • 41 Lafeuillade A, Solas C, Halfon P, Chadapaud S, Hittinger G, Lacarelle B. Differences in the detection of three HIV-1 protease inhibitors in non-blood compartments: clinical correlations. HIV Clin Trials 2002; 3 (1) 27-35
    CrossrefPubMedGoogle Scholar
  • 42 Gutmann C, Cusini A, Günthard HF , et al; Swiss HIV Cohort Study (SHCS). Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir. AIDS 2010; 24 (15) 2347-2354
    PubMedGoogle Scholar
  • 43 Haas DW, Clough LA, Johnson BW , et al. Evidence of a source of HIV type 1 within the central nervous system by ultraintensive sampling of cerebrospinal fluid and plasma. AIDS Res Hum Retroviruses 2000; 16 (15) 1491-1502
    CrossrefPubMedGoogle Scholar
  • 44 Yilmaz A, Fuchs D, Hagberg L , et al. Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the M61022 study. BMC Infect Dis 2006; 6: 63
    CrossrefPubMedGoogle Scholar
  • 45 Karlström O, Ståhle L, Perrin L, Tegude H, Sönnerborg A. Efficacy of nelfinavir-based treatment in the central nervous system of HIV-1 infected patients. Scand J Infect Dis 2006; 38 (5) 371-374
    CrossrefPubMedGoogle Scholar
  • 46 Moyle GJ, Sadler M, Buss N. Plasma and cerebrospinal fluid saquinavir concentrations in patients receiving combination antiretroviral therapy. Clin Infect Dis 1999; 28 (2) 403-404
    CrossrefPubMedGoogle Scholar
  • 47 Saumoy M, Tiraboschi J, Gutierrez M , et al. Viral response in stable patients switching to fosamprenavir/ritonavir monotherapy (the FONT Study). HIV Med 2011; 12 (7) 438-441
    CrossrefPubMedGoogle Scholar
  • 48 Letendre S, Mills A, Tashima K , et al. Distribution and antiviral activity in cerebrospinal fluid of the integrase inhibitor, dolutegravir: ING116070 Week 16 results. Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections, March–6, 2013; Atlanta, GA
    PubMedGoogle Scholar
  • 49 Yilmaz A, Gisslén M, Spudich S , et al. Raltegravir cerebrospinal fluid concentrations in HIV-1 infection. PLoS ONE 2009; 4 (9) e6877
    CrossrefPubMedGoogle Scholar
  • 50 Calcagno A, Bonora S, Bertucci R, Lucchini A, D'Avolio A, Di Perri G. Raltegravir penetration in the cerebrospinal fluid of HIV-positive patients. AIDS 2010; 24 (6) 931-932
    CrossrefPubMedGoogle Scholar
  • 51 Moore JP, Doms RW. The entry of entry inhibitors: a fusion of science and medicine. Proc Natl Acad Sci U S A 2003; 100 (19) 10598-10602
    CrossrefPubMedGoogle Scholar
  • 52 Price RW, Parham R, Kroll JL , et al. Enfuvirtide cerebrospinal fluid (CSF) pharmacokinetics and potential use in defining CSF HIV-1 origin. Antivir Ther 2008; 13 (3) 369-374
    PubMedGoogle Scholar
  • 53 Thomas SA. Drug transporters relevant to HIV therapy. J HIV Ther 2004; 9 (4) 92-96
    PubMedGoogle Scholar
  • 54 Yilmaz A, Watson V, Else L, Gisslèn M. Cerebrospinal fluid maraviroc concentrations in HIV-1 infected patients. AIDS 2009; 23 (18) 2537-2540
    CrossrefPubMedGoogle Scholar
  • 55 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) 606-609
    CrossrefPubMedGoogle Scholar
  • 56 Letendre S, Marquie-Beck J, Capparelli E , et al; CHARTER Group. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008; 65 (1) 65-70
    CrossrefPubMedGoogle Scholar
  • 57 Gisslén M, Hagberg L, Svennerholm B, Norkrans G. HIV-1 RNA is not detectable in the cerebrospinal fluid during antiretroviral combination therapy. AIDS 1997; 11 (9) 1194
    CrossrefPubMedGoogle Scholar
  • 58 Mellgren A, Antinori A, Cinque P , et al. Cerebrospinal fluid HIV-1 infection usually responds well to antiretroviral treatment. Antivir Ther 2005; 10 (6) 701-707
    PubMedGoogle Scholar
  • 59 Eggers C, Hertogs K, Stürenburg 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 (13) 1897-1906
    CrossrefPubMedGoogle Scholar
  • 60 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 (9) 1051-1061
    CrossrefPubMedGoogle Scholar
  • 61 Ellis RJ, Gamst AC, Capparelli E , et al. Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 2000; 54 (4) 927-936
    CrossrefPubMedGoogle Scholar
  • 62 Gisslén M, Svennerholm B, Norkrans G , et al. Cerebrospinal fluid and plasma viral load in HIV-1-infected patients with various anti-retroviral treatment regimens. Scand J Infect Dis 2000; 32 (4) 365-369
    CrossrefPubMedGoogle Scholar
  • 63 Yilmaz A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslén M. Persistent intrathecal immune activation in HIV-1-infected individuals on antiretroviral therapy. J Acquir Immune Defic Syndr 2008; 47 (2) 168-173
    CrossrefPubMedGoogle Scholar
  • 64 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 (12) 1686-1696
    CrossrefPubMedGoogle Scholar
  • 65 Dinoso JB, Kim SY, Wiegand AM , et al. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A 2009; 106 (23) 9403-9408
    CrossrefPubMedGoogle Scholar
  • 66 Dahl V, Lee E, Peterson J , et al. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis 2011; 204 (12) 1936-1945
    CrossrefPubMedGoogle Scholar
  • 67 Yilmaz A, Verhofstede C, D'Avolio A , et al. Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr 2010; 55 (5) 590-596
    CrossrefPubMedGoogle Scholar
  • 68 Mellgren A, Price RW, Hagberg L, Rosengren L, Brew BJ, Gisslén M. Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection. Neurology 2007; 69 (15) 1536-1541
    CrossrefPubMedGoogle Scholar
  • 69 Hagberg L, Cinque P, Gisslen M , et al. Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection. AIDS Res Ther 2010; 7: 15
    CrossrefPubMedGoogle Scholar
  • 70 Abdulle S, Hagberg L, Svennerholm B, Fuchs D, Gisslén M. Continuing intrathecal immunoactivation despite two years of effective antiretroviral therapy against HIV-1 infection. AIDS 2002; 16 (16) 2145-2149
    CrossrefPubMedGoogle Scholar
  • 71 Abdulle S, Hagberg L, Gisslén M. Effects of antiretroviral treatment on blood-brain barrier integrity and intrathecal immunoglobulin production in neuroasymptomatic HIV-1-infected patients. HIV Med 2005; 6 (3) 164-169
    CrossrefPubMedGoogle Scholar
  • 72 McArthur JC, Steiner J, Sacktor N, Nath A. Human immunodeficiency virus-associated neurocognitive disorders: Mind the gap. Ann Neurol 2010; 67 (6) 699-714
    CrossrefPubMedGoogle Scholar
  • 73 Hunt PW. HIV and inflammation: mechanisms and consequences. Curr HIV/AIDS Rep 2012; 9 (2) 139-147
    CrossrefPubMedGoogle Scholar
  • 74 Canestri A, Lescure FX, Jaureguiberry S , 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) 773-778
    CrossrefPubMedGoogle Scholar
  • 75 Peluso MJ, Ferretti F, Peterson J , et al. Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. AIDS 2012; 26 (14) 1765-1774
    CrossrefPubMedGoogle Scholar
  • 76 Lescure FX, Moulignier A, Savatovsky J , et al. CD8 encephalitis in HIV-infected patients receiving cART: a treatable entity. Clin Infect Dis 2013; 57 (1) 101-108
    CrossrefPubMedGoogle Scholar
  • 77 Gray F, Lescure FX, Adle-Biassette H , et al. Encephalitis with infiltration by CD8+ lymphocytes in HIV patients receiving combination antiretroviral treatment. Brain Pathol 2013; 23 (5) 525-533
    CrossrefPubMedGoogle Scholar
  • 78 Edén A, Fuchs D, Hagberg L , et al. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis 2010; 202 (12) 1819-1825
    CrossrefPubMedGoogle Scholar
  • 79 Lescure FX, Omland LH, Engsig FN , et al. Incidence and impact on mortality of severe neurocognitive disorders in persons with and without HIV infection: a Danish nationwide cohort study. Clin Infect Dis 2011; 52 (2) 235-243
    CrossrefPubMedGoogle Scholar
  • 80 Andersson LM, Hagberg L, Rosengren L, Fuchs D, Blennow K, Gisslén M. Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia—case report. BMC Infect Dis 2006; 6: 141
    CrossrefPubMedGoogle Scholar
  • 81 d'Arminio Monforte A, Cinque P, Mocroft A , et al; EuroSIDA Study Group. Changing incidence of central nervous system diseases in the EuroSIDA cohort. Ann Neurol 2004; 55 (3) 320-328
    CrossrefPubMedGoogle Scholar
  • 82 Robertson KR, Smurzynski M, Parsons TD , et al. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 2007; 21 (14) 1915-1921
    CrossrefPubMedGoogle Scholar
  • 83 Simioni S, Cavassini M, Annoni JM , et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 2010; 24 (9) 1243-1250
    PubMedGoogle Scholar
  • 84 Pumpradit W, Ananworanich J, Lolak S , et al; Southeast Asia Research Collaboration with Hawaii (SEARCH) 005 Protocol Team. Neurocognitive impairment and psychiatric comorbidity in well-controlled human immunodeficiency virus-infected Thais from the 2NN Cohort Study. J Neurovirol 2010; 16 (1) 76-82
    CrossrefPubMedGoogle Scholar
  • 85 Bonnet F, Amieva H, Marquant F , et al; S CO3 Aquitaine Cohort. Cognitive disorders in HIV-infected patients: are they HIV-related?. AIDS 2013; 27 (3) 391-400
    CrossrefPubMedGoogle Scholar
  • 86 Cysique LA, Brew BJ. Prevalence of non-confounded HIV-associated neurocognitive impairment in the context of plasma HIV RNA suppression. J Neurovirol 2011; 17 (2) 176-183
    CrossrefPubMedGoogle Scholar
  • 87 Muñoz-Moreno JA, Fumaz CR, Ferrer MJ , et al. Nadir CD4 cell count predicts neurocognitive impairment in HIV-infected patients. AIDS Res Hum Retroviruses 2008; 24 (10) 1301-1307
    CrossrefPubMedGoogle Scholar
  • 88 Gisslen M, Hagberg L, Rosengren L , et al. Defining and evaluating HIV-related neurodegenerative disease and its treatment targets: a combinatorial approach to use of cerebrospinal fluid molecular biomarkers. J Neuroimmune Pharmacol 2007; 2 (1) 112-119
    CrossrefPubMedGoogle Scholar
  • 89 Adkins JC, Noble S. Efavirenz. Drugs 1998; 56 (6) 1055-1064 , discussion 1065–1066
    CrossrefPubMedGoogle Scholar
  • 90 Lochet P, Peyrière H, Lotthé A, Mauboussin JM, Delmas B, Reynes J. Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz. HIV Med 2003; 4 (1) 62-66
    CrossrefPubMedGoogle Scholar
  • 91 Clifford DB, Evans S, Yang Y, Acosta EP, Ribaudo H, Gulick RM ; A5097s Study Team. Long-term impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals (ACTG 5097s). HIV Clin Trials 2009; 10 (6) 343-355
    CrossrefPubMedGoogle Scholar
  • 92 Robertson KR, Su Z, Margolis DM , et al; A5170 Study Team. Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort. Neurology 2010; 74 (16) 1260-1266
    CrossrefPubMedGoogle Scholar
  • 93 Marra CM, Zhao Y, Clifford DB , et al; AIDS Clinical Trials Group 736 Study Team. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 2009; 23 (11) 1359-1366
    CrossrefPubMedGoogle Scholar
  • 94 Alton EW, Stern M, Farley R , et al. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet 1999; 353 (9157) 947-954
    CrossrefPubMedGoogle Scholar
  • 95 Tovar-y-Romo LB, Bumpus NN, Pomerantz D , et al. Dendritic spine injury induced by the 8-hydroxy metabolite of efavirenz. J Pharmacol Exp Ther 2012; 343 (3) 696-703
    CrossrefPubMedGoogle Scholar
  • 96 Robertson K, Liner J, Meeker RB. Antiretroviral neurotoxicity. J Neurovirol 2012; 18 (5) 388-399
    CrossrefPubMedGoogle Scholar