Semin Neurol 2014; 34(01): 070-077
DOI: 10.1055/s-0034-1372344
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neurology and the Global HIV Epidemic

Ana-Claire Meyer
1   Department of Neurology, Yale University School of Medicine, New Haven, Connecticut
2   Research, Care, and Training Programme, Centre for Microbiology Research, Kenya Medical Research Institute, Kisumu, Kenya
› Author Affiliations
Further Information

Publication History

Publication Date:
08 April 2014 (online)

Abstract

The vast majority of people living with human immunodeficiency virus (HIV) infection reside in resource-limited settings. As compared with resource-rich settings, there are important differences in the epidemiology and outcomes of HIV infection in resource-limited settings. Nonetheless, little HIV neurology research occurs in these regions. We will first review clinical, epidemiological, and translational HIV neurology research originating from resource-limited settings. We will then discuss the barriers to conducting neurologic research, such as limited human resources, diagnostics, and access to medications. Finally, we will review existing initiatives to build capacity for research in resource-limited settings. Despite the barriers, there is growing interest in and opportunities for collaborative international neurologic research. Including diverse viral and human populations from across the globe in research opens possibilities for important implementation science, clinically oriented science, and basic science discoveries.

 
  • References

  • 1 World Health Organization. Number of people (all ages) living with HIV. Available at: http://www.who.int/gho/hiv/epidemic_status/cases_all/en/index.html . Accessed November 25, 2013
  • 2 World Health Organization. Anti-retroviral coverage among all age groups. Available at: http://www.who.int/gho/hiv/epidemic_response/ART_text/en/ . Accessed November 25, 2013
  • 3 Kaul R, Cohen CR, Chege D , et al. Biological factors that may contribute to regional and racial disparities in HIV prevalence. Am J Reprod Immunol 2011; 65 (3) 317-324
  • 4 Eisman S. Pruritic papular eruption in HIV. Dermatol Clin 2006; 24 (4) 449-457 , vi
  • 5 Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med 2011; 62: 157-170
  • 6 Achhra AC, Phanuphak P, Amin J. Long-term immunological outcomes in treated HIV-infected individuals in high-income and low-middle income countries. Curr Opin HIV AIDS 2011; 6 (4) 258-265
  • 7 Gupta A, Nadkarni G, Yang WT , et al. Early mortality in adults initiating antiretroviral therapy (ART) in low- and middle-income countries (LMIC): a systematic review and meta-analysis. PLoS ONE 2011; 6 (12) e28691
  • 8 Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med 2005; 2 (11) e298
  • 9 Bailey RC, Moses S, Parker CB , et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369 (9562) 643-656
  • 10 Gray RH, Kigozi G, Serwadda D , et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369 (9562) 657-666
  • 11 Baeten JM, Donnell D, Ndase P , et al; Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367 (5) 399-410
  • 12 Choopanya K, Martin M, Suntharasamai P , et al; Bangkok Tenofovir Study Group. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2013; 381 (9883) 2083-2090
  • 13 Grant RM, Lama JR, Anderson PL , et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363 (27) 2587-2599
  • 14 Thigpen MC, Kebaabetswe PM, Paxton LA , et al; TDF2 Study Group. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012; 367 (5) 423-434
  • 15 Howlett WP, Nkya WM, Mmuni KA, Missalek WR. Neurological disorders in AIDS and HIV disease in the northern zone of Tanzania. AIDS 1989; 3 (5) 289-296
  • 16 Perriëns JH, Mussa M, Luabeya MK , et al. Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire. J Acquir Immune Defic Syndr 1992; 5 (4) 333-340
  • 17 Maj M, Satz P, Janssen R , et al. WHO Neuropsychiatric AIDS study, cross-sectional phase II. Neuropsychological and neurological findings. Arch Gen Psychiatry 1994; 51 (1) 51-61
  • 18 Sacktor NC, Wong M, Nakasujja N , et al. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS 2005; 19 (13) 1367-1374
  • 19 Lawler K, Mosepele M, Ratcliffe S , et al. Neurocognitive impairment among HIV-positive individuals in Botswana: a pilot study. J Int AIDS Soc 2010; 13: 15
  • 20 Fernandes Filho SM, de Melo HR. Frequency and risk factors for HIV-associated neurocognitive disorder and depression in older individuals with HIV in northeastern Brazil. Int Psychogeriatr 2012; 24 (10) 1648-1655
  • 21 Njamnshi AK, Djientcheu VdeP, Fonsah JY, Yepnjio FN, Njamnshi DM, Muna WE. The International HIV Dementia Scale is a useful screening tool for HIV-associated dementia/cognitive impairment in HIV-infected adults in Yaoundé-Cameroon. J Acquir Immune Defic Syndr 2008; 49 (4) 393-397
  • 22 Njamnshi AK, Bissek AC, Ongolo-Zogo P , et al. Risk factors for HIV-associated neurocognitive disorders (HAND) in sub-Saharan Africa: the case of Yaoundé-Cameroon. J Neurol Sci 2009; 285 (1-2) 149-153
  • 23 Atashili J, Gaynes BN, Pence BW , et al. Prevalence, characteristics and correlates of a positive-dementia screen in patients on antiretroviral therapy in Bamenda, Cameroon: a cross-sectional study. BMC Neurol 2013; 13: 86
  • 24 Riedel D, Ghate M, Nene M , et al. Screening for human immunodeficiency virus (HIV) dementia in an HIV clade C-infected population in India. J Neurovirol 2006; 12 (1) 34-38
  • 25 Patel VN, Mungwira RG, Tarumbiswa TF, Heikinheimo T, van Oosterhout JJ. High prevalence of suspected HIV-associated dementia in adult Malawian HIV patients. Int J STD AIDS 2010; 21 (5) 356-358
  • 26 Oshinaike OO, Akinbami AA, Ojo OO, Ojini IF, Okubadejo UN, Danesi AM. Comparison of the Minimental State Examination Scale and the International HIV Dementia Scale in Assessing Cognitive Function in Nigerian HIV Patients on Antiretroviral Therapy. Aids Res Treat 2012; 2012: 581531
  • 27 Salawu FK, Bwala SA, Wakil MA, Bani B, Bukbuk DN, Kida I. Cognitive function in HIV-seropositive Nigerians without AIDS. J Neurol Sci 2008; 267 (1–2) 142-146
  • 28 Chan LG, Kandiah N, Chua A. HIV-associated neurocognitive disorders (HAND) in a South Asian population - contextual application of the 2007 criteria. BMJ Open 2012; 2 (1) e000662
  • 29 Robbins RN, Remien RH, Mellins CA, Joska JA, Stein DJ. Screening for HIV-associated dementia in South Africa: potentials and pitfalls of task-shifting. AIDS Patient Care STDS 2011; 25 (10) 587-593
  • 30 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) 371-378
  • 31 Singh D, Sunpath H, John S, Eastham L, Gouden R. The utility of a rapid screening tool for depression and HIV dementia amongst patients with low CD4 counts- a preliminary report. Afr J Psychiatry (Johannesbg) 2008; 11 (4) 282-286
  • 32 Ganasen KA, Fincham D, Smit J, Seedat S, Stein D. Utility of the HIV Dementia Scale (HDS) in identifying HIV dementia in a South African sample. J Neurol Sci 2008; 269 (1-2) 62-64
  • 33 Nakku J, Kinyanda E, Hoskins S. Prevalence and factors associated with probable HIV dementia in an African population: A cross-sectional study of an HIV/AIDS clinic population. BMC Psychiatry 2013; 13 (1) 126
  • 34 Holguin A, Banda M, Willen EJ , et al. HIV-1 effects on neuropsychological performance in a resource-limited country, Zambia. AIDS Behav 2011; 15 (8) 1895-1901
  • 35 Birbeck GL, Kvalsund MP, Byers PA , et al. Neuropsychiatric and socioeconomic status impact antiretroviral adherence and mortality in rural Zambia. Am J Trop Med Hyg 2011; 85 (4) 782-789
  • 36 Royal III W, Cherner M, Carr J , et al. Clinical features and preliminary studies of virological correlates of neurocognitive impairment among HIV-infected individuals in Nigeria. J Neurovirol 2012; 18 (3) 191-199
  • 37 Rodrigues RA, Oliveira RL, Grinsztejn B, Silva MT. Validity of the International HIV dementia scale in Brazil. Arq Neuropsiquiatr 2013; 71 (6) 376-379
  • 38 Haddow LJ, Floyd S, Copas A, Gilson RJ. A systematic review of the screening accuracy of the HIV Dementia Scale and International HIV Dementia Scale. PLoS ONE 2013; 8 (4) e61826
  • 39 Chalermchai T, Valcour V, Sithinamsuwan P , et al; SEARCH 007 and 011 study groups. Trail Making Test A improves performance characteristics of the International HIV Dementia Scale to identify symptomatic HAND. J Neurovirol 2013; 19 (2) 137-143
  • 40 Joska JA, Westgarth-Taylor J, Hoare J , et al. Validity of the International HIV Dementia Scale in South Africa. AIDS Patient Care STDS 2011; 25 (2) 95-101
  • 41 Waldrop-Valverde D, Nehra R, Sharma S , et al. Education effects on the International HIV Dementia Scale. J Neurovirol 2010; 16 (4) 264-267
  • 42 Lawler K, Jeremiah K, Mosepele M , et al. Neurobehavioral effects in HIV-positive individuals receiving highly active antiretroviral therapy (HAART) in Gaborone, Botswana. PLoS ONE 2011; 6 (2) e17233
  • 43 Wright E, Brew B, Arayawichanont A , et al. Neurologic disorders are prevalent in HIV-positive outpatients in the Asia-Pacific region. Neurology 2008; 71 (1) 50-56
  • 44 de Almeida SM, Ribeiro CE, de Pereira AP , et al. Neurocognitive impairment in HIV-1 clade C- versus B-infected individuals in Southern Brazil. J Neurovirol 2013; 19 (6) 550-556
  • 45 Heaton RK, Cysique LA, Jin H , et al; San Diego HIV Neurobehavioral Research Center Group. Neurobehavioral effects of human immunodeficiency virus infection among former plasma donors in rural China. J Neurovirol 2008; 14 (6) 536-549
  • 46 Zhang Y, Qiao L, Ding W , et al. An initial screening for HIV-associated neurocognitive disorders of HIV-1 infected patients in China. J Neurovirol 2012; 18 (2) 120-126
  • 47 Choi Y, Townend J, Vincent T , et al. Neurologic manifestations of human immunodeficiency virus-2: dementia, myelopathy, and neuropathy in West Africa. J Neurovirol 2011; 17 (2) 166-175
  • 48 Gupta JD, Satishchandra P, Gopukumar K , et al. Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India. J Neurovirol 2007; 13 (3) 195-202
  • 49 Sebit MB. Neuropsychiatric HIV-1 infection study: in Kenya and Zaire cross-sectional phase I and II. Cent Afr J Med 1995; 41 (10) 315-322
  • 50 Robertson K, Kumwenda J, Supparatpinyo K , et al; AIDS Clinical Trials Group. A multinational study of neurological performance in antiretroviral therapy-naïve HIV-1-infected persons in diverse resource-constrained settings. J Neurovirol 2011; 17 (5) 438-447
  • 51 Joska JA, Westgarth-Taylor J, Myer L , et al. Characterization of HIV-Associated Neurocognitive Disorders among individuals starting antiretroviral therapy in South Africa. AIDS Behav 2011; 15 (6) 1197-1203
  • 52 Cross HM, Combrinck MI, Joska JA. HIV-associated neurocognitive disorders: antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes. S Afr Med J 2013; 103 (10) 758-762
  • 53 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
  • 54 Wong MH, Robertson K, Nakasujja N , et al. Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan Africa. Neurology 2007; 68 (5) 350-355
  • 55 Sacktor N, Nakasujja N, Skolasky R , et al. Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa. Neurology 2006; 67 (2) 311-314
  • 56 Sacktor N, Nakasujja N, Skolasky RL , et al. Benefits and risks of stavudine therapy for HIV-associated neurologic complications in Uganda. Neurology 2009; 72 (2) 165-170
  • 57 Antinori A, Arendt G, Becker JT , et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007; 69 (18) 1789-1799
  • 58 Singh D, Joska JA, Goodkin K , et al. Normative scores for a brief neuropsychological battery for the detection of HIV-associated neurocognitive disorder (HAND) among South Africans. BMC Res Notes 2010; 3: 28
  • 59 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 (6) 868-876
  • 60 Joska JA, Gouse H, Paul RH, Stein DJ, Flisher AJ. Does highly active antiretroviral therapy improve neurocognitive function? A systematic review. J Neurovirol 2010; 16 (2) 101-114
  • 61 Carvalhal AS, Rourke SB, Belmonte-Abreu P, Correa J, Goldani LZ. Evaluation of neuropsychological performance of HIV-infected patients with minor motor cognitive dysfunction treated with highly active antiretroviral therapy. Infection 2006; 34 (6) 357-360
  • 62 Sacktor N, Nakasujja N, Okonkwo O , et al. Longitudinal neuropsychological test performance among HIV seropositive individuals in Uganda. J Neurovirol 2013; 19 (1) 48-56
  • 63 Clifford DB, Mitike MT, Mekonnen Y , et al. Neurological evaluation of untreated human immunodeficiency virus infected adults in Ethiopia. J Neurovirol 2007; 13 (1) 67-72
  • 64 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 (5) 781-790
  • 65 Kanmogne GD, Kuate CT, Cysique LA , et al. HIV-associated neurocognitive disorders in sub-Saharan Africa: a pilot study in Cameroon. BMC Neurol 2010; 10: 60
  • 66 Drotar D, Olness K, Wiznitzer M , et al. Neurodevelopmental outcomes of Ugandan infants with human immunodeficiency virus type 1 infection. Pediatrics 1997; 100 (1) E5
  • 67 Ruel TD, Boivin MJ, Boal HE , et al. Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts. Clin Infect Dis 2012; 54 (7) 1001-1009
  • 68 Tahan TT, Bruck I, Burger M, Cruz CR. Neurological profile and neurodevelopment of 88 children infected with HIV and 84 seroreverter children followed from 1995 to 2002. Braz J Infect Dis 2006; 10 (5) 322-326
  • 69 Vanprapar N, Kongstan N, Tritilanant P, Kottapat U, Durier Y, Tritilanant S. Developmental screening by the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) in HIV- infected children. J Med Assoc Thai 2005; 88 (Suppl. 08) S211-S214
  • 70 Maritz J, Benatar M, Dave JA , et al. HIV neuropathy in South Africans: frequency, characteristics, and risk factors. Muscle Nerve 2010; 41 (5) 599-606
  • 71 Wadley AL, Cherry CL, Price P, Kamerman PR. HIV neuropathy risk factors and symptom characterization in stavudine-exposed South Africans. J Pain Symptom Manage 2011; 41 (4) 700-706
  • 72 Evans D, Takuva S, Rassool M, Firnhaber C, Maskew M. Prevalence of peripheral neuropathy in antiretroviral therapy naïve HIV-positive patients and the impact on treatment outcomes—a retrospective study from a large urban cohort in Johannesburg, South Africa. J Neurovirol 2012; 18 (3) 162-171
  • 73 Pahuja M, Grobler A, Glesby MJ , et al. Effects of a reduced dose of stavudine on the incidence and severity of peripheral neuropathy in HIV-infected adults in South Africa. Antivir Ther 2012; 17 (4) 737-743
  • 74 Konchalard K, Wangphonpattanasiri K. Clinical and electrophysiologic evaluation of peripheral neuropathy in a group of HIV-infected patients in Thailand. J Med Assoc Thai 2007; 90 (4) 774-781
  • 75 Shikuma CM, McArthur JC, Ebenezer GJ , et al; SEARCH 014 Protocol Team. Ethnic differences in epidermal nerve fiber density. Muscle Nerve 2013; 48 (3) 462-464
  • 76 Kandiah PA, Atadzhanov M, Kvalsund MP, Birbeck GL. Evaluating the diagnostic capacity of a single-question neuropathy screen (SQNS) in HIV positive Zambian adults. J Neurol Neurosurg Psychiatry 2010; 81 (12) 1380-1381
  • 77 Cettomai D, Kwasa JK, Birbeck GL , et al. Screening for HIV-associated peripheral neuropathy in resource-limited settings. Muscle Nerve 2013; 48 (4) 516-524
  • 78 Mehta SA, Ahmed A, Kariuki BW , et al. Implementation of a validated peripheral neuropathy screening tool in patients receiving antiretroviral therapy in Mombasa, Kenya. Am J Trop Med Hyg 2010; 83 (3) 565-570
  • 79 Joseph J, Achim CL, Boivin MJ , et al. Global NeuroAIDS roundtable. J Neurovirol 2013; 19 (1) 1-9
  • 80 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 (5) 780-786
  • 81 Sacktor N, Nakasujja N, Robertson K, Clifford DB. HIV-associated cognitive impairment in sub-Saharan Africa—the potential effect of clade diversity. Nat Clin Pract Neurol 2007; 3 (8) 436-443
  • 82 Valcour VG, Ananworanich J, Agsalda M , et al; SEARCH 011 Protocol Team. HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients. PLoS ONE 2013; 8 (7) e70164
  • 83 Valcour VG, Shiramizu BT, Sithinamsuwan P , et al; Southeast Asia Research Collaboration with the University of Hawaii 001 protocol team. HIV DNA and cognition in a Thai longitudinal HAART initiation cohort: the SEARCH 001 Cohort Study. Neurology 2009; 72 (11) 992-998
  • 84 Heaps JM, Joska J, Hoare J , et al. Neuroimaging markers of human immunodeficiency virus infection in South Africa. J Neurovirol 2012; 18 (3) 151-156
  • 85 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
  • 86 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
  • 87 World Health Organization. World Federation of Neurology Atlas: Country Resources for Neurologic Disorders. Geneva, Switzerland: World Health Organization; 2004: 1-62
  • 88 Jowi JO. Provision of care to people with epilepsy in Kenya. East Afr Med J 2007; 84 (3) 97-99
  • 89 World Health Organization. The Global Campaign against Epilepsy, World Health Organization, International Bureau for Epilepsy, International League Against Epilepsy. Atlas: Epilepsy Care in the World. Geneva, Switzerland: World Health Organization; 2005: 1-96
  • 90 Kambugu A, Meya DB, Rhein J , et al. Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy. Clin Infect Dis 2008; 46 (11) 1694-1701
  • 91 Meyer AC, Dua T, Boscardin WJ, Escarce JJ, Saxena S, Birbeck GL. Critical determinants of the epilepsy treatment gap: a cross-national analysis in resource-limited settings. Epilepsia 2012; 53 (12) 2178-2185
  • 92 Ferreira M, Gendron F. Community-based participatory research with traditional and indigenous communities of the Americas: Historical context and future directions. Int J Crit Ped 2011; 3 (3) 153-168
  • 93 Flicker S, Travers R, Guta A, McDonald S, Meagher A. Ethical Dilemmas in Community-Based Participatory Research: Recommendations for Institutional Review Boards. Journal of Urban Health. 2007; 84 (4) 478-493
  • 94 Global Health Program for Fellows and Scholars, Fogarty International Center, U.S. National Institutes of Health. Available at: http://www.fic.nih.gov/Programs/Pages/scholars-fellows-global-health.aspx . Accessed December 30, 2013
  • 95 Heimburger DC, Carothers CL, Gardner P, Primack A, Warner TL, Vermund SH. Nurturing the global workforce in clinical research: the National Institutes of Health Fogarty International Clinical Scholars and Fellows Program. Am J Trop Med Hyg 2011; 85 (6) 971-978
  • 96 The Fogarty International Research Scholars Program, Vanderbilt University School of Medicine. Available at: ( http://fogartyscholars.org/program-history/the-scholars-program/ . Accessed December 30, 2013
  • 97 International Research Scientist Development Award, Fogarty International Center, U.S. National Institutes of Health. Available at: http://www.fic.nih.gov/programs/Pages/research-scientists.aspx . Accessed December 30, 2013
  • 98 Brain Disorders in the Developing World: Research Across the Lifespan, Fogarty International Center, U.S. National Institutes of Health. Available at: http://www.fic.nih.gov/Programs/Pages/brain-disorders.aspx . Accessed December 30, 2013
  • 99 Fogarty International Center, U.S. National Institutes of Health. Medical Education Partnership Initiative (MEPI). Available at: http://www.fic.nih.gov/programs/Pages/medical-education-africa.aspx . Accessed January 14, 2014
  • 100 International Clinical Research Fellowship, Doris Duke Charitable Foundation. Available at: http://www.ddcf.org/Programs/Medical-Research/Goals-and-Strategies/Build-the-Clinical-Research-Career-Ladder/International-Clinical-Research-Fellowship/ . Accessed December 30, 2013
  • 101 Canadian Institutes of Health Research and Quebec Population Health Research Network. Global Health Research Capacity Strengthening Program. Available at: http://www.pifrsm-ghrcaps.org/ . Accessed December 30, 2013
  • 102 Wellcome Trust. International Funding. Available at: http://www.wellcome.ac.uk/Funding/International/index.htm . Accessed December 30, 2013