Consequences of HAND for everyday functioning
With the introduction of combination antiretroviral therapy (cART), also as known as highly active antiretroviral therapy (HAART), in the mid 1990’s, the incidence of HIV-associated dementia (HAD), the most severe type of cognitive impairment, drastically decreased; however, the prevalence of milder forms of HIV-associated neurocognitive disorders (HAND) remains high (Heaton et al., 2011). A recent study of 1,555 persons living with HIV infection (HIV+) found that 52 percent had some form of neurocognitive impairment (Heaton et al., 2010), a rate not substantially different from that reported in the pre-cART era (Heaton, et al., 2011). HAND typically presents with a “frontal-striatal” profile, with impairments in learning/memory, attention/working memory, executive functions, speed of information processing and motor functioning. Such impairments can significantly disrupt everyday functioning, ranging from basic (e.g., dressing, grooming, bathing) to more complex (e.g., managing finances and medications, automobile driving) activities of daily living. While only severe dementia impacts basic skills, complex daily activities can be affected by even mild HAND.
Numerous studies, using various methods to ascertain “real world” functioning, have assessed the impact of HAND on everyday performance. One approach, self-report or collateral reports (e.g., asking a partner or family member how a patient is doing) is the easiest way to obtain information about a person’s functioning in real world settings; however, these reports can be affected by mood, impaired self-awareness and variability in subjective opinions. For example, depression is common in people with HIV, and people with depression tend to over-report deficits that are not objectively apparent (Millikin, Rourke, Halman, & Power, 2003). Conversely, individuals with poor insight may under-report functional deficits. Family members may have difficulty accepting their loved one’s struggles in everyday life and minimize the problems in collateral reports. Additionally, factors other than cognitive ability, such as motivation, physical condition and disability status can also affect what a person actually accomplishes in their day-to-day life (Marcotte, Scott, Kamat, & Heaton, 2009), and thus researchers have sought to establish new valid and reliable methods to assess real world functioning. One such approach is the use of objective, performance-based measures for use in laboratory/clinic settings to better determine an individual’s capacity to perform real world tasks.
Major outcomes that have been evaluated in HIV include vocational functioning, medication management and automobile driving, which we review here. As the majority of people living with HIV are of working age, employment is important to examine, given its relationship to independence and quality of life. Studies referencing the U.S. Department of Labor criteria that address the skills and knowledge needed to perform various jobs in the U.S. showed that neuropsychologically (NP) impaired HIV+ groups performed significantly worse on vocational tasks, compared to HIV-negative and HIV+ groups without impairment (Heaton et al., 2004; Heaton et al., 1996). Since the groups were comparable for past work history (indicating a similar vocational skill set), the findings suggest that the HIV+ NP impaired individuals had declined from previous levels of vocational functioning. Impairments in executive functions, learning, verbal abilities and attention/working memory were most predictive of performance on the vocational measures. While cART does appear to help employed HIV+ individuals remain employed, studies suggest that unemployed HIV+ individuals seldom re-enter the workforce (Martin, Arns, Batterham, Afifi, & Steckart, 2006). Unemployment in HIV has been associated with history of depressive disorder, physical limitations, continued NP impairment, and medical disability. HIV+ individuals receiving disability payments are less likely to return to work because of fear of losing benefits or health insurance. Employment status is thus multiply-determined and affected by not only by cognitive abilities but by these other factors as well.
It is essential that HIV+ individuals adhere to their prescribed medication regimens because poor adherence can lead to viral mutations, resulting in negative clinical virologic outcomes. The required level of medication adherence varies depending on the half-life of the medications, but it is generally recommended that patients take no less than 90-95 percent of their prescribed doses. Unfortunately, up to 40 percent of individuals may fail to take medications according to the dosage, time and dietary instructions (Chesney et al., 2000; Hinkin et al., 2004; Nieuwkerk et al., 2001). A number of cognitive functions have been related to adherence in HIV patients, such as learning and memory, executive functions and psychomotor speed (Barclay et al., 2007; Hinkin, et al., 2004). For example, poor prospective memory (remembering to perform an intended action in the face of ongoing distractions) has shown to be a good predictor of medication nonadherence (Woods et al., 2009).
It is challenging to assess medication adherence accurately by simply asking patients, because persons who report perfect to nearly perfect adherence may overestimate their actual rates by up to 10-20 percent (Arnsten et al., 2001; Levine et al., 2005). Another approach to determining adherence is to use “pill counts”. However, this method is based on the assumption that pills not in the bottles were indeed taken, and not lost or discarded. Also, this method does not confirm whether or not patients took the pills as scheduled (e.g., with food, at night). Electronic measuring devices, such as the Medication Event Monitoring System (MEMS), can produce a useful measure of adherence in research studies, especially for those who have NP impairment. These systems can automatically record the date, time, and duration of pill bottle opening, which can later be analyzed by researchers. Hinkin and colleagues (2004) assessed medication adherence by using the MEMS and found that older HIV+ individuals generally demonstrated better adherence than younger patients; however, older patients with cognitive impairment showed greatest difficulty in adhering to their medication regimen.
Performance-based measures, such as the Medication Management Test (MMT), have been utilized to evaluate patients’ capacity to manage medications. The MMT measures the patients’ ability to understand prescription labels and dispense medications. Although this may sound easy, patients are required to perform calculations to determine how many days a prescription will last and whether they have missed a dose of medicine based on a pill count. While yielding important information regarding the patient’s ability, performance on the MMT does not provide information on actual adherence. For instance, the patient’s family members and/or friends may help manage the medications (and thus provide good adherence), or performance in the real world may be affected by other factors, such as a chaotic environment or depression. When possible, it is best to use a multi-modal approach to assess adherence (e.g., self-report, collateral report and objective measures) (Liu et al., 2001; Marcotte, Scott, Hinkin, & Heaton, 2011). As reminders, approaches such as an online pager system (Safren, Hendriksen, Desousa, Boswell, & Mayer, 2003), text messaging (Hardy et al., 2011), phone voice service (Coomes et al., 2011), or GlowCaps (pill bottles with a wireless communication, which glow orange and play a melody to remind to take meds)(May, 2010) have shown promise for improving adherence.
Driving an automobile is one of the most complicated and difficult tasks in everyday life, requiring sustained attention, multitasking, visual scanning, planning, executing sequential movements and making judgments. As with the other activities of daily living, asking about driving performance may provide useful, but possibly inaccurate, information regarding how persons with HIV function in the real world. Driving events, such as moving violations and crashes, are typically rare, and may underestimate impaired driving. Advancing technology and lowering costs enable the use of semi-naturalistic driving assessments using driving simulators. With this technology, one can re-create realistic driving scenarios and include challenges such as emergency (e.g., pedestrian entering the roadway) or novel situations (e.g., rain, fog) without putting participants at risk (Marcotte, et al., 2011). Simulator studies have shown that neuropsychologically impaired HIV+ individuals have greater difficulty controlling lane position under conditions of high cognitive load, have more crashes, and commit more navigational errors than HIV- and cognitively intact HIV+ people. Individuals with HAND are also more likely to fail a structured on-road evaluation. Poor driving performance has been associated with impairments in executive functions, attention/working memory and speed of information processing (Marcotte et al., 1999; Marcotte et al., 2006; Marcotte et al., 2004).
Given the on-going problem of HAND, there is a growing interest in the role that cognitive rehabilitation may play in maximizing the functioning of impaired individuals. Various approaches, such as training in visual attention, information processing, memory and problem-solving skills have arisen, and may comprise the next generation of treatments for individuals with HIV/AIDS.
Despite the fact that HIV+ individuals can now anticipate a normal life span, pharmacological treatments have yet to solve the problem of reduced neuropsychological and everyday functioning. In addition to the impact of HIV-related cognitive impairment, it is also important to consider that other factors may affect both cognition and everyday functioning, such as other medical problems (e.g. hepatitis C virus infection), psychiatric issues (e.g., depression), and substance abuse (e.g., alcohol, methamphetamine). Finding a reliable method for identifying those individuals in need of assistance with daily activities, or guidance regarding compensatory strategies, remains a challenge, although researchers continue to seek new methods to address this knowledge gap.
About the authors
Maiko Sakamoto, PhD, was born in Matsuyama, Japan, and came to the U.S. to pursue her passion in psychology. She received her doctoral degree in clinical psychology with a neuropsychology concentration from Drexel University in Philadelphia. She has a diverse background focusing on cultural and individual differences in neuropsychology, including test development. Dr. Sakamoto developed Japanese verbal learning and verbal fluency tests as a part of her dissertation examining the usability and sensitivity of western neuropsychological tests in Japanese population. She has received several research awards including the Student Award and Diversity Award from the National Academy of Neuropsychology. Sakamoto is involved in multiple research projects in HIV at the HIV Neurobehavioral Research Program (HNRP), as a post-doctoral research fellow in the Department of Psychiatry at the University of California, San Diego (UCSD). Her research interests are everyday functioning in HIV, evaluation of measures to detect HIV-associated neurocognitive disorders (HAND), and development of a neuropsychological screening battery for mild HAND.
Thomas D. Marcotte, PhD, is an associate professor of psychiatry at UCSD. He has served as the Center Manager of the HIV Neurobehavioral Research Center for 15 years and is a co-director of CHARTER, a national multi-site study of the CNS impact of treatments for HIV. Dr. Marcotte’s areas of expertise include the neuropsychology of HIV, and the impact of mild impairments on everyday functioning, such as driving ability. Marcotte has been the principal investigator (PI) or co-investigator on numerous studies, and is currently the PI of a large study examining the neurocognitive effects of HIV in India, which is exploring the impact of antiretroviral treatment initiation on cognitive performance, as well as the role of host/viral factors in the development of HAND. He is co-editor of the book “Neuropsychology of Everyday Functioning” and has served on the editorial boards of both Neuropsychology and the Journal of the International Neuropsychological Society.
Arnsten, J.H., Demas, P.A., Farzadegan, H., Grant, R.W., Gourevitch, M.N., Chang, C.J. (2001). Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: comparison of self-report and electronic monitoring. Clinical Infectious Diseases, 33(8), 1417-1423. doi: CID001758 [pii] 10.1086/323201
Barclay, T.R., Hinkin, C.H., Castellon, S.A., Mason, K.I., Reinhard, M.J., Marion, S.D. (2007). Age-associated predictors of medication adherence in HIV-positive adults: health beliefs, self-efficacy, and neurocognitive status. Health Psychology, 26(1), 40-49. doi: 2006-23340-006 [pii] 10.1037/0278-6184.108.40.206
Chesney, M.A., Ickovics, J.R., Chambers, D.B., Gifford, A.L., Neidig, J., Zwickl, B. (2000). Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG adherence instruments. Patient Care Committee & Adherence Working Group of the Outcomes Committee of the Adult AIDS Clinical Trials Group (AACTG). AIDS Care, 12(3), 255-266. doi: 10.1080/09540120050042891
Coomes, C.M., Lewis, M.A., Uhrig, J.D., Furberg, R.D., Harris, J.L., & Bann, C.M. (2012). Beyond reminders: a conceptual framework for using short message service to promote prevention and improve healthcare quality and clinical outcomes for people living with HIV. AIDS Care, 24(3), 348-57. doi: 10.1080/09540121.2011.608421
Hardy, H., Kumar, V., Doros, G., Farmer, E., Drainoni, M.L., & Rybin, D. (2011). Randomized controlled trial of a personalized cellular phone reminder system to enhance adherence to antiretroviral therapy. AIDS Patient Care STDS, 25(3), 153-161. doi: 10.1089/apc.2010.0006
Heaton, R.K., Clifford, D.B., Franklin, D.R., Jr., Woods, S.P., Ake, C., & Vaida, F. (2010). HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology, 75(23), 2087-2096. doi: 75/23/2087 [pii]10.1212/WNL.0b013e318200d727
Heaton, R.K., Franklin, D.R., Ellis, R.J., McCutchan, J.A., Letendre, S.L., & Leblanc, S. (2011). HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. Journal of Neurovirology, 17(1), 3-16. doi: 10.1007/s13365-010-0006-1
Heaton, R.K., Marcotte, T.D., Mindt, M.R., Sadek, J., Moore, D.J., & Bentley, H. (2004). The impact of HIV-associated neuropsychological impairment on everyday functioning. Journal of the International Neuropsychological Society, 10(3), 317-331. doi: 10.1017/S1355617704102130 S1355617704102130 [pii]
Heaton, R.K., Marcotte, T.D., White, D.A., Ross, D., Meredith, K., & Taylor, M.J. (1996). Nature and vocational significance of neuropsychological impairment associated with HIV infection. Clinical Neuropsychologist, 10(1), 1-14. doi: 10.1080/13854049608406658
Hinkin, C.H., Hardy, D.J., Mason, K.I., Castellon, S.A., Durvasula, R.S., & Lam, M.N. (2004). Medication adherence in HIV-infected adults: effect of patient age, cognitive status, and substance abuse. AIDS, 18(Suppl 1), S19-25. doi: 00002030-200418001-00004 [pii]
Levine, A.J., Hinkin, C.H., Castellon, S.A., Mason, K.I., Lam, M.N., Perkins, A. (2005). Variations in patterns of highly active antiretroviral therapy (HAART) adherence. AIDS Behavior, 9(3), 355-362. doi: 10.1007/s10461-005-9009-y
Liu, H., Golin, C.E., Miller, L.G., Hays, R.D., Beck, C.K., Sanandaji, S. (2001). A comparison study of multiple measures of adherence to HIV protease inhibitors. Annals of Internal Medicine, 134(10), 968-977. doi: 200105150-00011 [pii]
Marcotte, T.D., Heaton, R.K., Wolfson, T., Taylor, M.J., Alhassoon, O., Arfaa, K. (1999). The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group. Journal of the International Neuropsychological Society, 5(7), 579-592.
Marcotte, T.D., Lazzaretto, D., Scott, J.C., Roberts, E., Woods, S.P., & Letendre, S. (2006). Visual attention deficits are associated with driving accidents in cognitively-impaired HIV-infected individuals. Journal of Clinical and Experimental Neuropsychology, 28(1), 13-28. doi: T83622752V545742 [pii] 10.1080/13803390490918048
Marcotte, T.D., Scott, J.C., Hinkin, C.H., & Heaton, R.K. (2011). Everyday impact of HIV-associated neurocognitive disorders. In H.E. Gendelman, I. Grant, I.P. Everall, H.S. Fox, H.A. Gelbard, S.A. Lipton & S. Swindells (Eds.), The neurology of AIDS (3rd ed.). USA: Oxford University Press.
Marcotte, T.D., Scott, J.C., Kamat, R., & Heaton, R.K. (2009). Neuropsychology and the prediction of everyday functioning. In T.D. Marcotte & I. Grant (Eds.), Neuropsychology of everyday functioning (pp. 5-38). New York: The Guilford Press.
Marcotte, T.D., Wolfson, T., Rosenthal, T.J., Heaton, R.K., Gonzalez, R., Ellis, R.J. (2004). A multimodal assessment of driving performance in HIV infection. Neurology, 63(8), 1417-1422. doi: 63/8/1417 [pii]
Martin, D.J., Arns, P.G., Batterham, P.J., Afifi, A.A., & Steckart, M.J. (2006). Workforce reentry for people with HIV/AIDS: intervention effects and predictors of success. Work, 27(3), 221-233.
May, M. (2010). Aiding adherence: five approaches to following prescriptions. Nat Med, 16(5), 504. doi: nm0510-504 [pii]10.1038/nm0510-504
Millikin, C.P., Rourke, S.B., Halman, M.H., & Power, C. (2003). Fatigue in HIV/AIDS is associated with depression and subjective neurocognitive complaints but not neuropsychological functioning. Journal of Clinical and Experimental Neuropsychology, 25(2), 201-215. doi: 10.1076/jcen.220.127.116.1144
Nieuwkerk, P.T., Sprangers, M.A., Burger, D.M., Hoetelmans, R.M., Hugen, P.W., Danner, S.A. (2001). Limited patient adherence to highly active antiretroviral therapy for HIV-1 infection in an observational cohort study. Archives of Internal Medicine, 161(16), 1962-1968. doi: ioi00746 [pii]
Safren, S.A., Hendriksen, E.S., Desousa, N., Boswell, S.L., & Mayer, K.H. (2003). Use of an on-line pager system to increase adherence to antiretroviral medications. AIDS Care, 15(6), 787-793. doi: 10.1080/09540120310001618630 H55VEFC99X4H7D9W [pii]
Woods, S.P., Dawson, M.S., Weber, E., Gibson, S., Grant, I., & Atkinson, J.H. (2009). Timing is everything: antiretroviral nonadherence is associated with impairment in time-based prospective memory. Journal of the International Neuropsychological Society, 15(1), 42-52. doi: S1355617708090012 [pii] 10.1017/S1355617708090012