Journal of NeuroVirology

, Volume 21, Issue 4, pp 415–421 | Cite as

Human immunodeficiency virus (HIV) modulates the associations between insulin resistance and cognition in the current combination antiretroviral therapy (cART) era: a study of the Women’s Interagency HIV Study (WIHS)

  • Victor Valcour
  • Leah H. Rubin
  • Phyllis Tien
  • Kathryn Anastos
  • Mary Young
  • Wendy Mack
  • Mardge Cohen
  • Elizabeth T. Golub
  • Howard Crystal
  • Pauline M. Maki
Article

Abstract

Cognitive impairment (CI) remains common despite access to combination antiretroviral therapy (cART); it has been linked to HIV-specific, HIV-related, and HIV-unrelated factors. Insulin resistance (IR) was associated with CI in the early cART era, when antiretroviral medications had greater mitochondrial and metabolic toxicity. We sought to examine these relationships in the current cART era of reduced antiretroviral toxicities. This study examined IR among non-diabetics in relation to a 1-h neuropsychological test battery among 994 women (659 HIV-infected and 335 HIV-uninfected controls) assessed between 2009 and 2011. The mean (standard deviation (SD)) age of the sample was 45.1 (9.3) years. The HIV-infected sample had a median interquartile range (IQR) cluster of differentiation 4 (CD4) T-lymphocyte count of 502 (310–727) cells/μL, and 54 % had undetectable plasma HIV RNA levels. Among all, the homeostasis model assessment (HOMA) of IR ranged from 0.25 to 37.14. In adjusted models, increasing HOMA was significantly associated with reduced performance on Letter-Number Sequencing (LNS) attention task (β = −0.10, p < 0.01) and on Hopkins Verbal Learning Test (HVLT) recognition (β = −0.10, p < 0.01) with weaker but statistically significant associations on phonemic fluency (β = −0.09, p = 0.01). An HIV*HOMA interaction effect was identified on the LNS attention task and Stroop trials 1 and 2, with worse performance in HIV-infected vs. HIV-uninfected women. In separate analyses, cohort members who had diabetes mellitus (DM) performed worse on the grooved pegboard test of psychomotor speed and manual dexterity. These findings confirm associations between both IR and DM on some neuropsychological tests and identify an interaction between HIV status and IR.

Keywords

HIV Insulin resistance Dementia Cognition cART 

References

  1. Bacon MC, von Wyl V, Alden C, Sharp G, Robison E, Hessol N, Gange S, Barranday Y, Holman S, Weber K, Young MA (2005) The women’s interagency HIV study: an observational cohort brings clinical sciences to the bench. Clin Diagn Lab Immunol 12(9):1013–1019PubMedCentralPubMedGoogle Scholar
  2. Barkan SE, Melnick SL, Preston-Martin S, Weber K, Kalish LA, Miotti P, Young M, Greenblatt R, Sacks H, Feldman J (1998) The women’s interagency HIV study. WIHS collaborative study group. Epidemiology 9(2):117–125PubMedCrossRefGoogle Scholar
  3. Boodram B, Plankey MW, Cox C, Tien PC, Cohen MH, Anastos K, Karim R, Hyman C, Hershow RC (2009) Prevalence and correlates of elevated body mass index among HIV-positive and HIV-negative women in the women’s interagency HIV study. AIDS Patient Care STDS 23(12):1009–1016PubMedCentralPubMedCrossRefGoogle Scholar
  4. Burdo TH, Weiffenbach A, Woods SP, Letendre S, Ellis RJ, Williams KC (2013) Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. AIDS 27(9):1387–1395PubMedCrossRefGoogle Scholar
  5. Clifford DB, Ances BM (2013) HIV-associated neurocognitive disorder. Lancet Infect Dis 13(11):976–986PubMedCentralPubMedCrossRefGoogle Scholar
  6. Craft S, Watson GS (2004) Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 3(3):169–178PubMedCrossRefGoogle Scholar
  7. Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, C. Group (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75(23):2087–2096PubMedCentralPubMedCrossRefGoogle Scholar
  8. Justice AC, Braithwaite RS (2012) Lessons learned from the first wave of aging with HIV. AIDS 26(Suppl 1):S11–S18PubMedCrossRefGoogle Scholar
  9. Maki PM, Rubin LH, Valcour V, Martin E, Crystal H, Young M, Weber KM, Manly J, Richardson J, Alden C, Anastos K (2015) Cognitive function in women with HIV: findings from the women's interagency HIV Study. Neurology 84(3):231–240. doi:10.1212/WNL.0000000000001151
  10. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419PubMedCrossRefGoogle Scholar
  11. McCutchan JA, Marquie-Beck JA, Fitzsimons CA, Letendre SL, Ellis RJ, Heaton RK, Wolfson T, Rosario D, Alexander TJ, Marra C, Ances BM, Grant I, C. Group (2012) Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology 78(7):485–492PubMedCentralPubMedCrossRefGoogle Scholar
  12. Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, Holmberg SD, Investigators HIVOS (2006) Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 43(1):27–34PubMedCrossRefGoogle Scholar
  13. Rubin LH, Sundermann EE, Cook JA, Martin EM, Golub ET, Weber KM, Cohen MH, Crystal H, Cederbaum JA, Anastos K, Young M, Greenblatt RM, Maki PM (2014) Investigation of menopausal stage and symptoms on cognition in human immunodeficiency virus-infected women. Menopause 21(9):997–1006PubMedCrossRefGoogle Scholar
  14. Srinivasa S, Grinspoon SK (2014) Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients. Eur J Endocrinol 170(5):R185–R202PubMedCrossRefGoogle Scholar
  15. Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U, Vlassi C, Giulianelli M, Galgani S, Antinori A, Narciso P (2007) Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 45(2):174–182PubMedCrossRefGoogle Scholar
  16. Valcour VG, Sacktor NC, Paul RH, Watters MR, Selnes OA, Shiramizu BT, Williams AE, Shikuma CM (2006) Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii aging with HIV cohort. J Acquir Immune Defic Syndr 43(4):405–410PubMedCrossRefGoogle Scholar
  17. Valcour V, Maki P, Bacchetti P, Anastos K, Crystal H, Young M, Mack WJ, Cohen M, Golub ET, Tien PC (2012) Insulin resistance and cognition among HIV-infected and HIV-uninfected adult women: the women’s interagency HIV study. AIDS Res Hum Retrovir 28(5):447–453PubMedCentralPubMedGoogle Scholar
  18. Valcour VG, Ananworanich J, Agsalda M, Sailasuta N, Chalermchai T, Schuetz A, Shikuma C, Liang CY, Jirajariyavej S, Sithinamsuwan P, Tipsuk S, Clifford DB, Paul R, Fletcher JL, Marovich MA, Slike BM, DeGruttola V, Shiramizu B, Team SP (2013) HIV DNA reservoir increases risk for cognitive disorders in cART-naive patients. PLoS One 8(7):e70164PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2015

Authors and Affiliations

  • Victor Valcour
    • 1
  • Leah H. Rubin
    • 2
  • Phyllis Tien
    • 3
  • Kathryn Anastos
    • 4
  • Mary Young
    • 5
  • Wendy Mack
    • 6
  • Mardge Cohen
    • 7
  • Elizabeth T. Golub
    • 8
  • Howard Crystal
    • 9
  • Pauline M. Maki
    • 2
  1. 1.Memory and Aging Center, Sandler Neurosciences CenterUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Department of PsychiatryUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Department of Medicine, Department of Veterans Affairs Medical CenterUniversity of California San FranciscoSan FranciscoUSA
  4. 4.Division of General Internal Medicine, Department of MedicineMontefiore Medical Center and Albert Einstein College of MedicineBronxUSA
  5. 5.Georgetown University Medical CenterWashingtonUSA
  6. 6.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  7. 7.Department of MedicinesStroger Hospital and Rush Medical CenterChicagoUSA
  8. 8.Bloomberg School of Public Health, Department of EpidemiologyJohns Hopkins UniversityBaltimoreUSA
  9. 9.Department of NeurologySUNY Downstate Medical CenterBrooklynUSA

Personalised recommendations