Semin Neurol 2018; 38(02): 238-246
DOI: 10.1055/s-0038-1649334
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Global Health Neurology: HIV/AIDS

Payal B. Patel
1   Division of Neuro-infectious Disease Clinical Research, Department of Neurology, Yale University, New Haven, Connecticut
,
Serena S. Spudich
2   Division of Neurological Infections and Global Neurology, Department of Neurology, Yale University, New Haven, Connecticut
› Author Affiliations
Further Information

Publication History

Publication Date:
23 May 2018 (online)

Abstract

With the advent of combination antiretroviral therapies, the mortality rate from HIV has declined, while the prevalence of long-term HIV-related neurologic complications continues to rise. Thirty-six million individuals are living with HIV around the world, many of whom reside in resource-limited settings. The majority of studies have focused on individuals residing in the developed world, while the impact of HIV disproportionately affects people living in developing countries. This review focuses on recent domestic and international studies regarding neurologic complications related to HIV, including opportunistic infections, peripheral neuropathy, cerebrovascular disease, and HIV-associated neurocognitive disorders, in light of the growing population affected by these conditions.

 
  • References

  • 1 United Nations AIDS. UNAIDS data 2017. Available at: http://www.unaids.org/en/resources/documents/2017/2017_data_book . Accessed August 23, 2017
  • 2 World Health Organization. Prevent HIV, test and treat all – WHO support for country impact. Available at: http://www.who.int/hiv/pub/progressreports/2016-progress-report/en . Accessed June 17, 2017
  • 3 Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med 2011; 62: 157-170
  • 4 Baeten JM, Brown ER, Hillier SL. Dapivirine vaginal ring for HIV-1 prevention. N Engl J Med 2017; 376 (10) 995-996
  • 5 Rerks-Ngarm S, Pitisuttithum P, Excler JL. , et al; RV305 Study Team. Randomized, double-blind evaluation of late boost strategies for HIV-uninfected vaccine recipients in the RV144 HIV vaccine efficacy trial. J Infect Dis 2017; 215 (08) 1255-1263
  • 6 Garvey L, Winston A, Walsh J. , et al; UK Collaborative HIV Cohort (CHIC) study. Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease. Neurology 2011; 76 (08) 693-700
  • 7 Bowen LN, Smith B, Reich D, Quezado M, Nath A. HIV-associated opportunistic CNS infections: pathophysiology, diagnosis and treatment. Nat Rev Neurol 2016; 12 (11) 662-674
  • 8 Asselman V, Thienemann F, Pepper DJ. , et al. Central nervous system disorders after starting antiretroviral therapy in South Africa. AIDS 2010; 24 (18) 2871-2876
  • 9 McCombe JA, Auer RN, Maingat FG, Houston S, Gill MJ, Power C. Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS: outcome and epidemiology. Neurology 2009; 72 (09) 835-841
  • 10 Venkataramana A, Pardo CA, McArthur JC. , et al. Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients. Neurology 2006; 67 (03) 383-388
  • 11 Bicanic T, Meintjes G, Rebe K. , et al. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr 2009; 51 (02) 130-134
  • 12 Johnson T, Nath A. Neurological complications of immune reconstitution in HIV-infected populations. Ann N Y Acad Sci 2010; 1184: 106-120
  • 13 Stoll M, Schmidt RE. Immune restoration inflammatory syndromes: apparently paradoxical clinical events after the initiation of HAART. Curr HIV/AIDS Rep 2004; 1 (03) 122-127
  • 14 Shelburne SA, Visnegarwala F, Darcourt J. , et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005; 19 (04) 399-406
  • 15 Bonham S, Meya DB, Bohjanen PR, Boulware DR. Biomarkers of HIV immune reconstitution inflammatory syndrome. Biomarkers Med 2008; 2 (04) 349-361
  • 16 Makadzange AT, Mothobi N. Delaying initiation of ART for 5 weeks improves survival in patients with HIV infection with cyrptococcal meningitis. Evid Based Med 2015; 20 (01) 15
  • 17 World Health Organization. TB/HIV: a clinical manual. Available at: http://apps.who.int/iris/bitstream/10665/42830/1/9241546344.pdf . Accessed May 3, 2017
  • 18 Scarpazza C, Prosperini L, De Rossi N. , et al; Italian PML group. To do or not to do? Plasma exchange and timing of steroid administration in progressive multifocal leukoencephalopathy. Ann Neurol 2017; 82 (05) 697-705
  • 19 Lescure FX, Moulignier A, Savatovsky J. , et al. CD8 encephalitis in HIV-infected patients receiving cART: a treatable entity. Clin Infect Dis 2013; 57 (01) 101-108
  • 20 Ghosh S, Chandran A, Jansen JP. Epidemiology of HIV-related neuropathy: a systematic literature review. AIDS Res Hum Retroviruses 2012; 28 (01) 36-48
  • 21 Robertson K, Jiang H, Kumwenda J. , et al; 5199 study team; AIDS Clinical Trials Group. Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study. Clin Infect Dis 2012; 55 (06) 868-876
  • 22 Hellmuth J, Fletcher JL, Valcour V. , et al; SEARCH 010/RV254 Study Group. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology 2016; 87 (02) 148-154
  • 23 Kranick SM, Nath A. Neurologic complications of HIV-1 infection and its treatment in the era of antiretroviral therapy. Continuum (Minneap Minn) 2012; 18 (6 Infectious Disease): 1319-1337
  • 24 Wang SX, Ho EL, Grill M. , et al. Peripheral neuropathy in primary HIV infection associates with systemic and central nervous system immune activation. J Acquir Immune Defic Syndr 2014; 66 (03) 303-310
  • 25 Pardo CA, McArthur JC, Griffin JW. HIV neuropathy: insights in the pathology of HIV peripheral nerve disease. J Peripher Nerv Syst 2001; 6 (01) 21-27
  • 26 Schifitto G, McDermott MP, McArthur JC. , et al; Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders. Incidence of and risk factors for HIV-associated distal sensory polyneuropathy. Neurology 2002; 58 (12) 1764-1768
  • 27 Marra CM, Boutin P, Collier AC. Screening for distal sensory peripheral neuropathy in HIV-infected persons in research and clinical settings. Neurology 1998; 51 (06) 1678-1681
  • 28 Morgello S, Estanislao L, Simpson D. , et al; Manhattan HIV Brain Bank. HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank. Arch Neurol 2004; 61 (04) 546-551
  • 29 Gonzalez-Duarte A, Robinson-Papp J, Simpson DM. Diagnosis and management of HIV-associated neuropathy. Neurol Clin 2008; 26 (03) 821-832 , x
  • 30 Lehmann HC, Chen W, Borzan J, Mankowski JL, Höke A. Mitochondrial dysfunction in distal axons contributes to human immunodeficiency virus sensory neuropathy. Ann Neurol 2011; 69 (01) 100-110
  • 31 Chen H, Clifford DB, Deng L. , et al. Peripheral neuropathy in ART-experienced patients: prevalence and risk factors. J Neurovirol 2013; 19 (06) 557-564
  • 32 Harrison TB, Smith B. Neuromuscular manifestations of HIV/AIDS. J Clin Neuromuscul Dis 2011; 13 (02) 68-84
  • 33 Simpson DM, Brown S, Tobias J. ; NGX-4010 C107 Study Group. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 2008; 70 (24) 2305-2313
  • 34 Phillips N, Amos T, Kuo C. , et al. HIV-associated cognitive impairment in perinatally infected children: a meta-analysis. Pediatrics 2016; 138 (05) e20160893
  • 35 Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system. J Acquir Immune Defic Syndr 2012; 60 (04) 351-358
  • 36 Sico JJ, Chang CC, So-Armah K. , et al; Veterans Aging Cohort Study. HIV status and the risk of ischemic stroke among men. Neurology 2015; 84 (19) 1933-1940
  • 37 Chow FC, He W, Bacchetti P. , et al. Elevated rates of intracerebral hemorrhage in individuals from a US clinical care HIV cohort. Neurology 2014; 83 (19) 1705-1711
  • 38 Hasse B, Ledergerber B, Furrer H. , et al; Swiss HIV Cohort Study. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis 2011; 53 (11) 1130-1139
  • 39 Vinikoor MJ, Napravnik S, Floris-Moore M, Wilson S, Huang DY, Eron JJ. Incidence and clinical features of cerebrovascular disease among HIV-infected adults in the Southeastern United States. AIDS Res Hum Retroviruses 2013; 29 (07) 1068-1074
  • 40 Lang S, Mary-Krause M, Cotte L. , et al; French Hospital Database on HIV-ANRS CO4. Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS 2010; 24 (08) 1228-1230
  • 41 Chow F, Wilson MR, Wu K. , et al. Stroke incidence highest in women and black HIV-infected participants in ALLRT cohort. Abstracted presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 22–25, 2016; Boston, MA
  • 42 Li JZ, Arnold KB, Lo J. , et al. Differential levels of soluble inflammatory markers by human immunodeficiency virus controller status and demographics. Open Forum Infect Dis 2015; 2 (01) ofu117
  • 43 Fitch KV, Srinivasa S, Abbara S. , et al. Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis 2013; 208 (11) 1737-1746
  • 44 De Socio GV, Ricci E, Maggi P. , et al; CISAI Study Group. Prevalence, awareness, treatment, and control rate of hypertension in HIV-infected patients: the HIV-HY study. Am J Hypertens 2014; 27 (02) 222-228
  • 45 Gutierrez J, Elkind MS, Marshall RS. Cardiovascular profile and events of US adults 20-49 years with HIV: results from the NHANES 1999-2008. AIDS Care 2013; 25 (11) 1385-1391
  • 46 Tesoriero JM, Gieryic SM, Carrascal A, Lavigne HE. Smoking among HIV positive New Yorkers: prevalence, frequency, and opportunities for cessation. AIDS Behav 2010; 14 (04) 824-835
  • 47 Soontornniyomkij V, Umlauf A, Chung SA. , et al. HIV protease inhibitor exposure predicts cerebral small vessel disease. AIDS 2014; 28 (09) 1297-1306
  • 48 Chow FC, Li Y, Hu Y. , et al. Relationship between HIV infection, antiretroviral therapy, inflammatory markers, and cerebrovascular endothelial function among adults in urban China. J Acquir Immune Defic Syndr 2017; 74 (03) 339-346
  • 49 Sabin CA, Ryom L, De Wit S. , et al; D:A:D Study Group. Associations between immune depression and cardiovascular events in HIV infection. AIDS 2013; 27 (17) 2735-2748
  • 50 Tenorio AR, Zheng Y, Bosch RJ. , et al. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis 2014; 210 (08) 1248-1259
  • 51 González-Scarano F, Martín-García J. The neuropathogenesis of AIDS. Nat Rev Immunol 2005; 5 (01) 69-81
  • 52 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
  • 53 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
  • 54 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
  • 55 McArthur JC, Brew BJ. HIV-associated neurocognitive disorders: is there a hidden epidemic?. AIDS 2010; 24 (09) 1367-1370
  • 56 Woods SP, Iudicello JE, Moran LM, Carey CL, Dawson MS, Grant I. ; HIV Neurobehavioral Research Center Group. HIV-associated prospective memory impairment increases risk of dependence in everyday functioning. Neuropsychology 2008; 22 (01) 110-117
  • 57 Simioni S, Cavassini M, Annoni JM. , et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 2010; 24 (09) 1243-1250
  • 58 Thames AD, Kim MS, Becker BW. , et al. Medication and finance management among HIV-infected adults: the impact of age and cognition. J Clin Exp Neuropsychol 2011; 33 (02) 200-209
  • 59 Heaton RK, Franklin Jr DR, Deutsch R. , et al; CHARTER Group. Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. Clin Infect Dis 2015; 60 (03) 473-480
  • 60 Sacktor N, Skolasky RL, Seaberg E. , et al. Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study. Neurology 2016; 86 (04) 334-340
  • 61 Vogel A, Stokholm J, Gade A, Andersen BB, Hejl AM, Waldemar G. Awareness of deficits in mild cognitive impairment and Alzheimer's disease: do MCI patients have impaired insight?. Dement Geriatr Cogn Disord 2004; 17 (03) 181-187
  • 62 Chiao S, Rosen HJ, Nicolas K. , et al. Deficits in self-awareness impact the diagnosis of asymptomatic neurocognitive impairment in HIV. AIDS Res Hum Retroviruses 2013; 29 (06) 949-956
  • 63 Obermeit LC, Beltran J, Casaletto KB. , et al; CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Group. Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining “symptomatic” versus “asymptomatic” HAND. J Neurovirol 2017; 23 (01) 67-78
  • 64 Antinori A, Arendt G, Becker JT. , et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007; 69 (18) 1789-1799
  • 65 Sacktor N, Nakasujja N, Okonkwo O. , et al. Longitudinal neuropsychological test performance among HIV seropositive individuals in Uganda. J Neurovirol 2013; 19 (01) 48-56
  • 66 Sacktor N, Nakasujja N, Skolasky R. , et al. Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa. Neurology 2006; 67 (02) 311-314
  • 67 Sacktor N, Nakasujja N, Skolasky RL. , et al. HIV subtype D is associated with dementia, compared with subtype A, in immunosuppressed individuals at risk of cognitive impairment in Kampala, Uganda. Clin Infect Dis 2009; 49 (05) 780-786
  • 68 Sacktor N, Nakasujja N, Redd AD. , et al. HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda. Metab Brain Dis 2014; 29 (02) 261-268
  • 69 Rippeth JD, Heaton RK, Carey CL. , et al; HNRC Group. Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc 2004; 10 (01) 1-14
  • 70 Hilsabeck RC, Castellon SA, Hinkin CH. Neuropsychological aspects of coinfection with HIV and hepatitis C virus. Clin Infect Dis 2005; 41 (Suppl. 01) S38-S44
  • 71 Wright EJ, Grund B, Cysique LA. , et al; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Factors associated with neurocognitive test performance at baseline: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med 2015; 16 (Suppl. 01) 97-108
  • 72 Valcour VG, Rubin LH, Obasi MU. , et al; Womenʼs Interagency HIV Study Protocol Team. Liver fibrosis linked to cognitive performance in HIV and hepatitis C. J Acquir Immune Defic Syndr 2016; 72 (03) 266-273
  • 73 Cysique LA, Jin H, Franklin Jr DR. , et al; HNRC Group. Neurobehavioral effects of HIV-1 infection in China and the United States: a pilot study. J Int Neuropsychol Soc 2007; 13 (05) 781-790
  • 74 Cysique LA, Brew BJ. Prevalence of non-confounded HIV-associated neurocognitive impairment in the context of plasma HIV RNA suppression. J Neurovirol 2011; 17 (02) 176-183
  • 75 Marquine MJ, Umlauf A, Rooney AS. , et al; HIV Neurobehavioral Research Program (HNRP) Group. The veterans aging cohort study index is associated with concurrent risk for neurocognitive impairment. J Acquir Immune Defic Syndr 2014; 65 (02) 190-197
  • 76 Vo QT, Cox C, Li X. , et al. Neuropsychological test performance before and after HIV-1 seroconversion: the Multicenter AIDS Cohort Study. J Neurovirol 2013; 19 (01) 24-31
  • 77 Haddow LJ, Laverick R, Daskalopoulou M. , et al; Cognitive Impairment in People with HIV in the European Region (CIPHER) Study Group. Multicenter European prevalence study of neurocognitive impairment and associated factors in HIV positive patients. AIDS Behav 2018; 22 (05) 1573-1583
  • 78 Kore I, Ananworanich J, Valcour V. , et al; RV254/SEARCH 010 Study Group. Neuropsychological impairment in acute HIV and the effect of immediate antiretroviral therapy. J Acquir Immune Defic Syndr 2015; 70 (04) 393-399
  • 79 Cysique LA, Vaida F, Letendre S. , et al. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology 2009; 73 (05) 342-348
  • 80 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 (01) 65-70
  • 81 Cusini A, Vernazza PL, Yerly S. , et al; Swiss HIV Cohort Study. 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 (01) 28-35
  • 82 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 (03) 357-365
  • 83 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
  • 84 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 (06) 343-355
  • 85 Ciccarelli N, Fabbiani M, Di Giambenedetto S. , et al. Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients. Neurology 2011; 76 (16) 1403-1409
  • 86 Ma Q, Vaida F, Wong J. , et al; CHARTER Group. Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients. J Neurovirol 2016; 22 (02) 170-178
  • 87 National Institute of Health. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0
  • 88 Kelly CM, van Oosterhout JJ, Ngwalo C. , et al. HIV asociated neurocognitive disorders (HAND) in Malawian adults and effect on adherence to combination anti-retroviral therapy: a cross-sectional study. PLoS One 2014; 9 (06) e98962
  • 89 Pumpradit W, Ananworanich K, Lolak S. , et al. 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 (01) 76-82
  • 90 Joska JA, Gouse H, Paul RH. , et al. Does highly active antiretroviral therapy improve neurocognitive function? A systematic review. J Neurovirol 2010; 16 (02) 101-114
  • 91 Zhao T, Wei B, Long J. , et al. Cognitive disorders in HIV-infected and AIDS patients in Guangxi, China. J Neurovirol 2015; 21 (01) 32-42