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)
- 273 Downloads
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.
KeywordsHIV Insulin resistance Dementia Cognition cART
Dr. Rubin’s efforts are supported by 1 K01-MH098798. Data in this manuscript were collected by the Women’s Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen), U01-AI-034993; Metropolitan Washington WIHS (Mary Young), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women’s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Alexandra Levine and Marek Nowicki), U01-HD-032632 (WIHS I–WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women’s Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA).
Conflict of interest
The authors, Victor Valcour M.D., Ph.D., Leah H. Rubin Ph.D., Phyllis Tien M.D., Kathryn Anastos M.D., Mary Young M.D., Wendy Mack Ph.D., Mardge Cohen M.D., Elizabeth T. Golub Ph.D., Howard Crystal M.D., and Pauline M. Maki Ph.D., declare that they have no conflict of interest.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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