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01-04-2015

Association between brain volumes and HAND in cART-naïve HIV+ individuals from Thailand

Authors: Jodi M. Heaps, Pasiri Sithinamsuwan, Robert Paul, Sukalaya Lerdlum, Mantana Pothisri, David Clifford, Somporn Tipsuk, Stephanie Catella, Edgar Busovaca, James L. K. Fletcher, Benjamin Raudabaugh, Silvia Ratto-Kim, Victor Valcour, Jintanat Ananworanich, on behalf of the SEARCH 007/011 study groups

Published in: Journal of NeuroVirology | Issue 2/2015

Abstract

This study aimed to determine the effects of human immunodeficiency virus (HIV) on brain structure in HIV-infected individuals with and without HIV-associated neurocognitive disorders (HAND). Twenty-nine HIV-uninfected controls, 37 HIV+, treatment-naïve, individuals with HAND (HIV+HAND+; 16 asymptomatic neurocognitive impairment (ANI), 12 mild neurocognitive disorder (MND), and 9 HIV-associated dementia HAD), and 37 HIV+, treatment-naïve, individuals with normal cognitive function (HIV+HAND−) underwent magnetic resonance imaging (MRI) and neuropsychological assessment. The HIV-infected participants had a mean (SD) age of 35 (7) years, mean (interquartile range (IQR)) CD4 count of 221 (83–324), and mean (IQR) log₁₀ plasma viral load of 4.81 (4.39–5.48). Six regions of interest were selected for analyses including total and subcortical gray matter, total white matter, caudate, corpus callosum, and thalamus. The HIV+/HAND+ group exhibited significantly smaller brain volumes compared to the HIV-uninfected group in subcortical gray and total gray matter; however, there were no statistically significant differences in brain volumes between the HIV+HAND+ and HIV+HAND− groups or between HIV+/HAND− and controls. CD4 count at time of combination antiretroviral therapy (cART) initiation was associated with total and subcortical gray matter volumes but not with cognitive measures. Plasma viral load correlated with neuropsychological performance but not brain volumes. The lack of significant differences in brain volumes between HIV+HAND+ and HIV+HAND− suggests that brain atrophy is not a sensitive measure of HAND in subjects without advanced immunosuppression. Alternatively, current HAND diagnostic criteria may not sufficiently distinguish patients based on MRI measures of brain volumes.

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Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M… Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 69(18):1789–1799

Blackstone K, Moore DJ, Heaton RK, Franklin DR, Woods SP, Clifford DB… Grant I (2012) Diagnosing symptomatic HIV-associated neurocognitive disorders: self-report versus performance-based assessment of everyday functioning. J Int Neuropsychol Soc, 18(01):79–88

Chiao S, Rosen HJ, Nicolas K, Wendelken LA, Alcantar O, Rankin KP… Valcour V (2013) Deficits in self-awareness impact the diagnosis of asymptomatic neurocognitive impairment in HIV. AIDS Res Human Retrovir. 29(6):949–956

Childs EA, Lyles RH, Selnes OA, Chen B, Miller EN, Cohen BA… McArthur JC (1999) Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy. Neurology. 52(3):607–607

de Almeida SM, Ribeiro CE, de Pereira AP, Badiee J, Cherner M, Smith D… Ellis RJ (2013) Neurocognitive impairment in HIV-1 clade C-versus B-infected individuals in Southern Brazil. J Neurovirol. 19(6):550–556

Ellis RJ, Evans SR, Clifford DB, Moo LR, McArthur JC, Collier AC… Robertson K (2005) Clinical validation of the NeuroScreen. J Neurovirol. 11(6):503–511

Farias ST, Mungas D, Reed B, Carmichael O, Beckett L, Harvey D… DeCarli C (2012) Maximal brain size remains an important predictor of cognition in old age, independent of current brain pathology. Neurobiol Aging. 33(8):1758–1768

Fischl B, van der Kouwe A, Destrieux C, Halgren E, Segonne F, Salat DH, Busa E, Seidman LJ, Goldstein J, Kennedy D, Caviness V, Makris N, Rosen B, Dale AM (2004) Automatically parcellating the human cerebral cortex. Cereb Cortex 14:11–22CrossRefPubMed

Foley JM, Wright MJ, Gooding AL, Ettenhofer M, Kim M, Choi M… Hinkin CH (2011) Operationalization of the updated diagnostic algorithm for classifying HIV-related cognitive impairment and dementia. Int Psychogeriatr. 23(05):835–843

Free SL, Bergin PS, Fish DR, Cook MJ, Shorvon SD, Stevens JM (1995) Methods for normalization of hippocampal volumes measured with MR. Am J Neuroradiol 16(4):637–643PubMed

Gisslén M, Price RW, Nilsson S (2011) The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence? BMC Infect Dis 11(1):356CrossRefPubMedCentralPubMed

Grant I, Franklin DR, Deutsch R, Woods SP, Vaida F, Ellis RJ… Heaton RK (2014) Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology. 10–1212

Heaps JM, Joska J, Hoare J Ortega M, Agrawal A, Seedat S… Paul R (2012) Neuroimaging markers of human immunodeficiency virus infection in South Africa. J Neurovirol. 18(3):151–156

Heaps J, Valcour V, Chalermchai T, Paul R, Rattanamanee S, Siangphoe U… Ananworanich J (2013) Development of normative neuropsychological performance in Thailand for the assessment of HIV-associated neurocognitive disorders. J Clin Exp Neuropsychol. 35(1):1–8

Heaton RK, Clifford DB, Franklin DR, Woods SP, Ake C, Vaida F… Grant I (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy CHARTER Study. Neurology. 75(23):2087–2096

Holt JL, Kraft-Terry SD, Chang L (2012) Neuroimaging studies of the aging HIV-1-infected brain. J Neurovirol 18(4):291–302CrossRefPubMedCentralPubMed

Jernigan TL, Archibald SL, Fennema-Notestine C, Taylor MJ, Theilmann RJ, Julaton MD… Grant I (2011) Clinical factors related to brain structure in HIV: the CHARTER study. J Neurovirol. 17(3):248–257

Kallianpur KJ, Valcour VG, Lerdlum S, Busovaca E, Agsalda M, Sithinamsuwan P… Ananworanich J (2014) HIV DNA in CD14+ reservoirs is associated with regional brain atrophy in combination antiretroviral therapy naive patients. AIDS. 500:14–00085

Katz S (1983) Assessing self-maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc

Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186CrossRefPubMed

Maj M, D’Elia L, Satz P, Janssen R, Zaudig M, Uchiyama C… Chervinsky A (1993) Evaluation of two new neuropsychological tests designed to minimize cultural bias in the assessment of HIV-1 seropositive persons: a WHO study. Arch Clin Neuropsychol. 8(2):123–135

Maj M, Janssen R, Starace F, Zaudig M, Satz P, Sughondhabirom B… Sartorius N (1994) WHO neuropsychiatric AIDS study, cross-sectional phase I: study design and psychiatric findings. Arch Gen Psychiatry. 51(1):39–49

Meyer AC, Boscardin WJ, Kwasa JK, Price RW (2013) 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. Neuroepidemiology 41(3–4):208–216CrossRefPubMedCentralPubMed

Ortega M, Heaps JM, Joska J, Vaida F, Seedat S, Stein DJ… Ances BM (2013) HIV clades B and C are associated with reduced brain volumetrics. J Neurovirol. 19(5):479–487

Paul R, Cohen R, Navia B, & Tashima K (2002) Relationships between cognition and structural neuroimaging findings in adults with human immunodeficiency virus type-1. Neurosci Biobehav Rev 26(3):353–359

Paul RH, Joska JA, Woods C, Seedat S, Engelbrecht S, Hoare J… Stein DJ (2014) Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease. J Neurovirol. 20(6):627–35

Perneczky R, Wagenpfeil S, Lunetta KL, Cupples LA, Green RC, Decarli C… Kurz A (2010) Head circumference, atrophy, and cognition implications for brain reserve in Alzheimer disease. Neurology. 75(2):137–142

Ranjbar S, Rajsbaum R, Goldfeld AE (2006) Transactivator of transcription from HIV type 1 subtype E selectively inhibits TNF gene expression via interference with chromatin remodeling of the TNF locus. J Immunol 176(7):4182–4190CrossRefPubMed

Rao VR, Sas AR, Eugenin EA, Siddappa NB, Bimonte-Nelson H, Berman JW… Prasad VR (2008) HIV-1 clade-specific differences in the induction of neuropathogenesis. J Neurosci. 28(40):10010–10016.

Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S… RV254/SEARCH 010 protocol teams (2012) Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. PloS One. 7(11):e49272

Suwanwelaa N, Phanuphak P, Phanthumchinda K, Suwanwela NC, Tantivatana J, Ruxrungtham K… Hanvanich M (2000) Magnetic resonance spectroscopy of the brain in neurologically asymptomatic HIV-infected patients. Magn Reson Imaging. 18(7):859–865

Tate DF, Neeley ES, Norton MC, Tschanz JT, Miller MJ, Wolfson L… Bigler ED (2011) Intracranial volume and dementia: some evidence in support of the cerebral reserve hypothesis. Brain Res. 1385:151–162

Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, Becker JT (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A 102(43):15647–15652CrossRefPubMedCentralPubMed

Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P… Volberding PA (2012) Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society—USA panel. Jama. 308(4):387–402

Torti C, Focà E, Cesana BM, Lescure FX (2011) Asymptomatic neurocognitive disorders in patients infected by HIV: fact or fiction? BMC Med 9(1):138CrossRefPubMedCentralPubMed

Tucker KA, Robertson KR, Lin W, Smith JK, An H, Chen Y… Hall CD (2004) Neuroimaging in human immunodeficiency virus infection. J. Neuroimmunol. 157(1):153–162

Valcour V, Yee P, Williams AE, Shiramizu B, Watters M, Selnes O… Sacktor N (2006) Lowest ever CD4 lymphocyte count (CD4 nadir) as a predictor of current cognitive and neurological status in human immunodeficiency virus type 1 infection—The Hawaii Aging with HIV Cohort. J Neurovirol. 12(5):387–391

Valcour VG, Sithinamsuwan P, Nidhinandana S, Thitivichianlert S, Ratto-Kim S, Apateerapong W… Shikuma CM (2007) Neuropsychological abnormalities in patients with dementia in CRF 01_AE HIV-1 infection. Neurology. 68(7):525–527

Valcour V, Sithinamsuwan P, Letendre S, Ances B (2011) Pathogenesis of HIV in the central nervous system. Curr HIV/AIDS Rep 8(1):54–61CrossRefPubMedCentralPubMed

Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D… Ananworanich J (2012) Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis. 206(2):275–282

Valcour VG, Ananworanich J, Agsalda M, Sailasuta N, Chalermchai T, Schuetz A… SEARCH 011 Protocol Team (2013) HIV DNA reservoir increases risk for cognitive disorders in cART-naive patients. PloS One. 8(7):e70164

Vivithanaporn P, Heo G, Gamble J, Krentz HB, Hoke A, Gill MJ, Power C (2010) Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study. Neurology 75(13):1150–1158CrossRefPubMedCentralPubMed

Wirachsilp P, Kantakamalakul W, Foongladda S, Chuenchitra T, Kohriangudom S, Athipanyasilp N… Sutthent R (2007) Surveillance of subtype and genetic variation of the circulating strains of HIV-1 in Thailand. Southeast Asian J Trop Med Public Health. 38:814–827

World Health Organization (WHO) (2013) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. World Health Organization, Geneva, <http://www.who.int/hiv/pub/guidelines/arv2013/en/>

Title: Association between brain volumes and HAND in cART-naïve HIV+ individuals from Thailand
Authors: Jodi M. Heaps
Pasiri Sithinamsuwan
Robert Paul
Sukalaya Lerdlum
Mantana Pothisri
David Clifford
Somporn Tipsuk
Stephanie Catella
Edgar Busovaca
James L. K. Fletcher
Benjamin Raudabaugh
Silvia Ratto-Kim
Victor Valcour
Jintanat Ananworanich
on behalf of the SEARCH 007/011 study groups
Publication date: 01-04-2015
Publisher: Springer US
Published in: Journal of NeuroVirology / Issue 2/2015
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-014-0309-8

2024 ASCO Annual Meeting

Springer Medicine

Association between brain volumes and HAND in cART-naïve HIV+ individuals from Thailand

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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