Introduction to current issues in HIV-associated neurocognitive disorders (HAND)

Articles on aging with HIV, growing up HIV+, at-risk persons suffering from mental illness and substance abuse, and treatments for HAND

HIV-associated neurocognitive disorders (HAND) remain prevalent despite widespread availability of antiretroviral medications in the developed world. Data from the recent CNS HIV Anti-retroviral Effects Research study (CHARTER), a U.S. multi-site study of close to 1600 HIV+ participants, found a prevalence of HAND exceeding 50 percent. Neuropsychological impairments can have consequences for employment, independence in everyday functioning, and quality of life. Based largely on the work of the HIV Neurobehavioral Research Center at the University of California San Diego, the current classifications of HAND include Asymptomatic Neurocognitive Impairment (ANI), where deficits are detected with comprehensive neuropsychological testing, but patients do not perceive changes in daily functioning; Mild Neurocognitive Disorder (MND), characterized by mild-to-moderate deficits and mild losses of independence in instrumental activities of daily living; and the most severe manifestation, HIV-Associated Dementia (HAD), which affects only a minority of HIV+ persons and consists of moderate-to-severe neuropsychological deficits and marked declines in the ability to carry out everyday activities.

While a lot has been learned since the beginning of the epidemic, there continue to be vigorous research efforts underway to understand the mechanisms by which HIV injures the brain and how damage can be prevented or reversed. Some of this work involves examining genetic and other characteristics of both the virus and the host that may predict how the disease progresses. In recent years, researchers have also focused on the very early stages of infection, aiming to understand the incidence, timing, and predictors of HAND during this early period. Significant research is ongoing to ascertain whether virologic control with combination antiretroviral therapy (cART) can arrest or improve neuropsychological problems, and what may be the effects of prolonged exposure to cART. Novel non-antiretroviral therapies are also being investigated, as are cognitive-behavioral interventions to improve functioning.

In this issue, neuroAIDS experts and their students doing cutting-edge research review current topics in HIV neurocognitive disorders. We start with a pressing question: As modern therapies allow HIV+ individuals the possibility of a normal lifespan, what is known about aging with HIV? Dr. Charles Hinkin and Dr. April Thames tell us.

On the opposite end of the developmental spectrum, what about growing up HIV+? While perinatal infection is a dwindling problem in the developed world, children still face this challenge in areas with high HIV prevalence and poor access to prenatal antiretrovirals. Dr. Sharon Nichols reviews the pediatric neuropsychology of HIV.

Persons suffering from serious mental illness are at increased risk for HIV infection and adverse health consequences. Dr. David Moore and Carolina Posada discuss the health-care challenges posed by this vulnerable population.

Those who are substance-addicted are also more vulnerable to contract HIV, as well as to transmit it, largely as a result of engagement in risky behaviors. I review what is known about the manifestations of HAND in the context of substance abuse, focusing on methamphetamine, which has been demonstrated to affect brain functioning and is linked to HIV transmission both through injection use and sexual contact.

Dr. Maiko Sakamoto and Dr. Thomas Marcotte answer the "So what?" question: What are the implications on HAND for everyday functioning? They discuss the “real world” consequences of neuropsychological impairment both in terms of the ability to function independently, as well as downstream health-related outcomes.

The final sections address treatment. Dr. David Croteau explains how antiretrovirals work to suppress HIV replication and discusses various therapeutic avenues that can impact HAND. Erica Weber and Dr. Steven Woods provide perspectives on neuro-rehabilitative approaches to HAND.

We hope that you will find this issue informative and a good resource for those wishing to learn more about neuroAIDS.

I would like to extend heartfelt thanks to Dr. John Anderson for the opportunity to share this research update on neurocognitive aspects of HIV/AIDS, for his tireless leadership of the APA’s Office on AIDS, and for his commitment to improving the lives of those affected by HIV.

About the author

Mariana Cherner, PhD Mariana Cherner, PhD, graduated with a BA in psychology from Cornell University. She obtained her PhD at the SDSU/UCSD Joint Doctoral Program in Clinical Psychology in 1997, specializing in neuropsychology and behavioral medicine. She completed a clinical psychology internship at the University of Washington, where she also received postdoctoral training in neuropsychology. Dr. Cherner is Associate Professor In Residence in the Department of Psychiatry at UCSD and director of the Interdisciplinary Research Fellowship in NeuroAIDS, as well as a faculty member in the SDSU/UCSD Joint Doctoral Program in Clinical Psychology. Cherner has an interest in the role of coexisting conditions such as hepatitis C and stimulant drug (methamphetamine, MDMA) abuse in the manifestation of HIV-associated neurocognitive disorders. Her current research  focuses on genetically determined individual differences in vulnerability to brain dysfunction among methamphetamine users with HIV. She conducts her work within the UCSD HIV Neurobehavioral Research Programs, where she is an investigator on a number of federally funded grants related to neuroAIDS. The other focus of her research is in the area of cross-cultural neuropsychology, with a special interest in culturally competent assessment of cognitive abilities and everyday functioning in Spanish speakers. She also participates in training and mentorship of predoctoral students and postdoctoral researchers.

References

Cherner, M., Bousman, C., Letendre, S., Barron, D., Vaida, F., Atkinson, J.H., Heaton, R., Everall, I., Grant, I., the HNRC Group. (2010). Cytochrome P450-2D6 extensive metabolizers are more vulnerable to methamphetamine-associated neurocognitive impairment: Preliminary findings. JINS, 16, 890–901.

Cherner, M., Suarez, P., Casey, C., Deiss, R., Letendre, S., Marcotte, T., Vaida, F., Atkinson, J.H., Grant, I., Heaton, R., the HNRC Group. (2010). Methamphetamine use parameters do not predict neuropsychological impairment in currently abstinent dependent adults. Drug and Alcohol Dependence, 106, 154-163.

Cherner, M., Cysique, L., Heaton, R.K., Marcotte, T.D., Ellis, R.J., Masliah, E., Grant, I,. & the HNRC Group. (2007). Neuropathologic confirmation of definitional criteria for HIV associated neurocognitive disorders. Journal of Neurovirology, 13(1), 23-28.

Cherner, M., Suarez, P., Lazzaretto, D., Artiola i Fortuny, L, Rivera Mindt, M, Marcotte, T, Grant, I., Heaton, R., the HNRC Group. (2007). Demographically corrected norms for the Brief Visuospatial Memory Test-Revised and Hopkins Verbal Learning Test-Revised in Monolingual Spanish Speakers from the U.S. – Mexico Border Region. Archives of Clinical Neuropsychology, 22(3), 343-353.

Cherner, M., Letendre, S.L., Heaton, R.K., Durelle, J., Marquie-Beck, J., Gragg, B., Grant, I. (2005). Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology, 64, 1343-1347.

Cherner, M., Ellis, R.J., Lazzaretto, D., Young, C., Mindt, M.R., Atkinson, J.H., Grant, I., Heaton, R.K., the HNRC Group. (2004). Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings. AIDS, 18(suppl 1), S27-S34.

Cherner, M., Masliah, E., Ellis, R.J., Marcotte, T.D., Moore, D.J., Grant, I., Heaton, R.K. (2002). Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis. Neurology, 59(10), 1563-1567.