Skip to main content

Advertisement

SpringerLink
Log in

Treatment of HIV in the CNS: Effects of Antiretroviral Therapy and the Promise of Non-Antiretroviral Therapeutics

  • Central Nervous System and Cognition (I Grant, Section Editor)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

  1. Valcour V, Chalermchai T, Sailasuta N, et al. Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis. 2012;206(2):275–82. This study demonstrated the presence of viral particles in the CSF of patients acutely infected with HIV as early as eight days after estimated transmission.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Peluso MJ, Meyerhoff DJ, Price RW, et al. Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis. 2013;207(11):1703–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Jessen Krut J, Mellberg T, Price RW, et al. Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients. PLoS One. 2014;9(2):e88591. This study demonstrated elevations in neurofilament light chain, a marker of neuronal injury, even in asymptomatic individuals with well-controlled HIV infection.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789–99.

    Article  CAS  PubMed  Google Scholar 

  5. Heaton RK, Marcotte TD, Mindt MR, et al. The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc. 2004;10(3):317–31.

    Article  PubMed  Google Scholar 

  6. Woods SP, Weber E, Weisz BM, Twamley EW, Grant I, Group HIVNRP. Prospective memory deficits are associated with unemployment in persons living with HIV infection. Rehabil Psychol. 2011;56(1):77–84.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Doyle K, Weber E, Atkinson JH, Grant I, Woods SP, Group HIVNRP. Aging, prospective memory, and health-related quality of life in HIV infection. AIDS Behav. 2012;16(8):2309–18.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Cattie JE, Doyle K, Weber E, Grant I, Woods SP, Group HIVNRP. Planning deficits in HIV-associated neurocognitive disorders: component processes, cognitive correlates, and implications for everyday functioning. J Clin Exp Neuropsychol. 2012;34(9):906–18.

    Article  PubMed Central  PubMed  Google Scholar 

  9. 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):1765–74.

    Article  CAS  PubMed  Google Scholar 

  10. 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):773–8.

    Article  PubMed  Google Scholar 

  11. 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):101–8.

    Article  CAS  PubMed  Google Scholar 

  12. 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):525–33.

    Article  PubMed  Google Scholar 

  13. Joska JA, Fincham DS, Stein DJ, Paul RH, Seedat S. Clinical correlates of HIV-associated neurocognitive disorders in South Africa. AIDS Behav. 2010;14(2):371–8.

    Article  PubMed  Google Scholar 

  14. McArthur JC, Hoover DR, Bacellar H, et al. Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology. 1993;43(11):2245–52.

    Article  CAS  PubMed  Google Scholar 

  15. Heaton RK, Clifford DB, Franklin Jr DR, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75(23):2087–96.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. 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):235–43. This large study demonstrated that patients with severe HIV-associated neurocognitive impairment had worse morbidity and mortality outcomes than HIV-uninfected patients with unrelated neurocognitive impairment.

    Article  PubMed  Google Scholar 

  17. Sacktor N, McDermott MP, Marder K, et al. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002;8(2):136–42.

    Article  PubMed  Google Scholar 

  18. Cysique LA, Maruff P, Brew BJ. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol. 2004;10(6):350–7.

    Article  PubMed  Google Scholar 

  19. Heaton RK, Franklin DR, Ellis RJ, et al. 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. This study compared HIV-infected individuals from pre- and cART-era cohorts and further supported earlier observations that neurocognitive impairment is more common in the cART era, but has shifted toward mild impairment.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Weber E, Blackstone K, Woods SP. Cognitive neurorehabilitation of HIV-associated neurocognitive disorders: a qualitative review and call to action. Neuropsychol Rev. 2013;23(1):81–98.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Churchill MJ, Wesselingh SL, Cowley D, et al. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol. 2009;66(2):253–8.

    Article  PubMed  Google Scholar 

  22. Thompson KA, Cherry CL, Bell JE, McLean CA. Brain cell reservoirs of latent virus in presymptomatic HIV-infected individuals. Am J Pathol. 2011;179(4):1623–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Gray LR, Cowley D, Crespan E, et al. Reduced basal transcriptional activity of central nervous system-derived HIV type 1 long terminal repeats. AIDS Res Hum Retrovir. 2013;29(2):365–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  24. 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):2395–407.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Best BM, Letendre SL, Koopmans P, et al. Low cerebrospinal fluid concentrations of the nucleotide HIV reverse transcriptase inhibitor, tenofovir. J Acquir Immune Defic Syndr. 2012;59(4):376–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Yilmaz A, Watson V, Dickinson L, Back D. Efavirenz pharmacokinetics in cerebrospinal fluid and plasma over a 24-hour dosing interval. Antimicrob Agents Chemother. 2012;56(9):4583–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Mora-Peris B, Mackie NE, Suan D, Cooper DA, Brew BJ, Winston A. Raltegravir resistance in the cerebrospinal fluid. Infection. 2013;41(3):731–4.

    Article  CAS  PubMed  Google Scholar 

  29. Letendre S, Marquie-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(1):65–70.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Marra CM, Zhao Y, Clifford DB, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS. 2009;23(11):1359–66.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Tozzi V, Balestra P, Salvatori MF, et al. Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr. 2009;52(1):56–63.

    Article  CAS  PubMed  Google Scholar 

  32. Letendre SL, McCutchan JA, Childers ME, et al. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol. 2004;56(3):416–23.

    Article  PubMed  Google Scholar 

  33. Vassallo M, Durant J, Biscay V, 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.

    Article  CAS  PubMed  Google Scholar 

  34. Smurzynski M, Wu K, Letendre S, et al. Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort. AIDS. 2011;25(3):357–65.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Garvey L, Surendrakumar V, Winston A. Low rates of neurocognitive impairment are observed in neuro-asymptomatic HIV-infected subjects on effective antiretroviral therapy. HIV Clin Trials. 2011;12(6):333–8.

    Article  CAS  PubMed  Google Scholar 

  36. Casado JL, Marin A, Moreno A, et al. Central nervous system antiretroviral penetration and cognitive functioning in largely pretreated HIV-infected patients. J Neurovirol. 2014;20(1):54–61.

    Article  CAS  PubMed  Google Scholar 

  37. Shikuma CM, Nakamoto B, Shiramizu B, et al. Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV. Antivir Ther. 2012;17(7):1233–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Kelly KM, Beck SE, Pate KA, et al. Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain. AIDS. 2013;27(18):F21–F28.

  39. Ellis RJ, Letendre S, Vaida F, et al. Randomized trial of central nervous system-targeted antiretrovirals for HIV-associated neurocognitive disorder. Clin Infect Dis. 2014;58(7):1015–22.

    Article  CAS  PubMed  Google Scholar 

  40. Dalpiaz A, Ferraro L, Perrone D, et al. Brain uptake of a Zidovudine prodrug after nasal administration of solid lipid microparticles. Mol Pharm. 2014;11(5):1550–61.

    Article  CAS  PubMed  Google Scholar 

  41. Cysique LA, Vaida F, Letendre S, et al. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology. 2009;73(5):342–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Ellis RJ, Badiee J, Vaida F, et al. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS. 2011;25(14):1747–51.

    Article  CAS  PubMed  Google Scholar 

  43. 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):753–60. This study characterized the extent of neuroinflammation present in individuals during the first year of HIV infection, even in those with low CSF HIV RNA levels.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Wang SX, Ho EL, Grill M, et al. Peripheral neuropathy in primary HIV infection associates with systemic and CNS immune activation. J Acquir Immune Defic Syndr. 2014;66(3):303–10.

  45. Moore DJ, Letendre SL, Morris S, et al. Neurocognitive functioning in acute or early HIV infection. J Neurovirol. 2011;17(1):50–7.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Atkinson JH, Higgins JA, Vigil O, et al. Psychiatric context of acute/early HIV infection. The NIMH Multisite Acute HIV Infection Study: IV. AIDS Behav. 2009;13(6):1061–7.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Gold JA, Grill M, Peterson J, et al. Longitudinal characterization of depression and mood states beginning in primary HIV infection. AIDS Behav. 2014;18(6):1124–32.

    Article  PubMed  Google Scholar 

  48. Weber E, Morgan EE, Iudicello JE, et al. Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection. J Neurovirol. 2013;19(1):65–74.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. 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):371–9. This cross-sectional study is the first to suggest that early initiation of treatment may mitigate neuropsychological impairment in individuals with HIV.

    Article  PubMed Central  PubMed  Google Scholar 

  50. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Mellgren A, Antinori A, Cinque P, et al. Cerebrospinal fluid HIV-1 infection usually responds well to antiretroviral treatment. Antivir Ther. 2005;10(6):701–7.

    CAS  PubMed  Google Scholar 

  52. 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(13):1897–906.

    Article  PubMed  Google Scholar 

  53. Eden A, Andersson LM, Andersson O, et al. Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naive HIV-1-infected patients. AIDS Res Hum Retrovir. 2010;26(5):533–40.

    Article  CAS  PubMed  Google Scholar 

  54. Harrington PR, Schnell G, Letendre SL, et al. Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course. AIDS. 2009;23(8):907–15.

    Article  PubMed Central  PubMed  Google Scholar 

  55. 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(16):10830–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Eggers C, Muller O, Thordsen I, Schreiber M, Methner A. Genetic shift of env V3 loop viral sequences in patients with HIV-associated neurocognitive disorder during antiretroviral therapy. J Neurovirol. 2013;19(6):523–30.

    Article  CAS  PubMed  Google Scholar 

  57. Cinque P, Brew BJ, Gisslen M, Hagberg L, Price RW. Cerebrospinal fluid markers in central nervous system HIV infection and AIDS dementia complex. Handb Clin Neurol. 2007;85:261–300.

    Article  PubMed  Google Scholar 

  58. Yilmaz A, Yiannoutsos CT, Fuchs D, et al. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy. J Neuroinflammation. 2013;10:62.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Lentz MR, Kim JP, Westmoreland SV, et al. Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology. 2005;235(2):461–8.

    Article  PubMed  Google Scholar 

  60. Ernst T, Jiang CS, Nakama H, Buchthal S, Chang L. Lower brain glutamate is associated with cognitive deficits in HIV patients: a new mechanism for HIV-associated neurocognitive disorder. J Magn Reson Imaging. 2010;32(5):1045–53.

    Article  PubMed Central  PubMed  Google Scholar 

  61. Harezlak J, Buchthal S, Taylor M, 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.

    Article  CAS  PubMed  Google Scholar 

  62. Cardenas VA, Meyerhoff DJ, Studholme C, et al. Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy. J Neurovirol. 2009;15(4):324–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Gongvatana A, Harezlak J, Buchthal S, et al. Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy. J Neurovirol. 2013;19(3):209–18.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Garvey LJ, Pavese N, Politis M, et al. Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART. AIDS. 2014;28(1):67–72.

    Article  CAS  PubMed  Google Scholar 

  65. Lentz MR, Kim WK, Lee V, et al. Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection. Neurology. 2009;72(17):1465–72.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Lentz MR, Kim WK, Kim H, et al. Alterations in brain metabolism during the first year of HIV infection. J Neurovirol. 2011;17(3):220–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Sailasuta N, Ross W, Ananworanich J, et al. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PLoS One. 2012;7(11):e49272.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Hua X, Boyle CP, Harezlak J, et al. Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment. NeuroImage Clin. 2013;3:132–42.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Harezlak J, Cohen R, Gongvatana A, et al. Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART. J Neurovirol. 2014;20(3):294–303.

    Article  CAS  PubMed  Google Scholar 

  70. Granziera C, Daducci A, Simioni S, et al. Micro-structural brain alterations in aviremic HIV + patients with minor neurocognitive disorders: a multi-contrast study at high field. PLoS One. 2013;8(9):e72547.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Pfefferbaum A, Rogosa DA, Rosenbloom MJ, et al. Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled, longitudinal magnetic resonance imaging study. Neurobiol Aging. 2014;35(7):1755–68.

    Article  PubMed  Google Scholar 

  72. Valcour VG, Ananworanich J, Agsalda M, et al. HIV DNA reservoir increases risk for cognitive disorders in cART-naive patients. PLoS One. 2013;8(7):e70164.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Fumaz CR, Munoz-Moreno JA, Molto J, et al. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence. J Acquir Immune Defic Syndr. 2005;38(5):560–5.

    Article  PubMed  Google Scholar 

  74. Robertson K, Liner J, Meeker RB. Antiretroviral neurotoxicity. J Neurovirol. 2012;18(5):388–99.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Brown LA, Jin J, Ferrell D, 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.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Akay C, Cooper M, Odeleye A, et al. Antiretroviral drugs induce oxidative stress and neuronal damage in the central nervous system. J Neurovirol. 2014;20(1):39–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Ferretti F, Gianotti N, Lazzarin A, Cinque P. Central nervous system HIV infection in “less-drug regimen” antiretroviral therapy simplification strategies. Semin Neurol. 2014;34(1):78–88.

    Article  PubMed  Google Scholar 

  79. Uthman OA, Abdulmalik JO. Adjunctive therapies for AIDS dementia complex. Cochrane Database Syst Rev. 2008;3, CD006496.

    PubMed  Google Scholar 

  80. Ances BM, Letendre SL, Alexander T, Ellis RJ. Role of psychiatric medications as adjunct therapy in the treatment of HIV associated neurocognitive disorders. Int Rev Psychiatry. 2008;20(1):89–93.

    Article  PubMed  Google Scholar 

  81. Simioni S, Cavassini M, Annoni JM, et al. Rivastigmine for HIV-associated neurocognitive disorders: a randomized crossover pilot study. Neurology. 2013;80(6):553–60.

    Article  CAS  PubMed  Google Scholar 

  82. Zhao Y, Navia BA, Marra CM, et al. Memantine for AIDS dementia complex: open-label report of ACTG 301. HIV Clin Trials. 2010;11(1):59–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Sacktor N, Miyahara S, Deng L, et al. Minocycline treatment for HIV-associated cognitive impairment: results from a randomized trial. Neurology. 2011;77(12):1135–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Nakasujja N, Miyahara S, Evans S, et al. Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment. Neurology. 2013;80(2):196–202.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Probasco JC, Spudich SS, Critchfield J, et al. Failure of atorvastatin to modulate CSF HIV-1 infection: results of a pilot study. Neurology. 2008;71(7):521–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Soontornniyomkij V, Umlauf A, Chung SA, et al. HIV protease inhibitor exposure predicts cerebral small vessel disease. AIDS. 2014;28(9):1297–1306. This cross-sectional study of the California NeuroAIDS Tissue Network found a correlation between protease inhibitor use and cerebral small vessel disease, suggesting a mechanism by which antiretroviral agents might contribute to HAND.

  87. Johnson TP, Patel K, Johnson KR, et al. Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein. Proc Natl Acad Sci U S A. 2013;110(33):13588–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Mapstone M, Hilton TN, Yang H, et al. Poor aerobic fitness may contribute to cognitive decline in HIV-infected older adults. Aging Dis. 2013;4(6):311–9.

    Article  PubMed Central  PubMed  Google Scholar 

  89. Dufour CA, Marquine MJ, Fazeli PL, et al. Physical exercise is associated with less neurocognitive impairment among HIV-infected adults. J Neurovirol. 2013;19(5):410–7.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Michael J. Peluso and Serena Spudich declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Medicine, Brigham and Women’s Hospital, 75 Francis St, Boston, MA, 02115, USA

    Michael J. Peluso

  2. Department of Neurology, Yale University School of Medicine, PO Box 208018, New Haven, CT, 06520, USA

    Serena Spudich

Authors
  1. Michael J. Peluso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serena Spudich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Serena Spudich.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peluso, M.J., Spudich, S. Treatment of HIV in the CNS: Effects of Antiretroviral Therapy and the Promise of Non-Antiretroviral Therapeutics. Curr HIV/AIDS Rep 11, 353–362 (2014). https://doi.org/10.1007/s11904-014-0223-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-014-0223-y

Keywords

Search

Navigation