Substance Abuse and HIV: Genetics and Disease Progression

Investigator: Ruth Greenblatt, MD
Sponsor: State University of New York System

Location(s): United States


Examines psychiatric co-morbidity in HIV. Since the advent of HAART, the number of older adults (> 50 years old) living with HIV has increased to more than 60,000 persons in the U.S., accounting for almost 15% of HIV/AIDS cases; this percentage is expected to grow331. As a result of this convergence of HIV/AIDS and aging, health issues typically seen in those suffering from chronic diseases now present in HIV-infected adults. The natural history of HIV as a chronic disease, symptom manifestation, and competing risks from aging, drug toxicity, and comorbid conditions are pressing issues not yet characterized in HIV-infected older adults332, 333. Only now are the effects of HAART treatment over extended periods of time being realized, including its likely interaction with various comorbidities. With extensive follow up, the WIHS is uniquely situated to measure how HIV and its treatment combine with comorbidities and age-related effects to impact mental and physical impairment. 

Highlights during WIHS III include: 
• Neurocognitive disease. Baseline Neurocognitive evaluations were done on HIV/HCV coinfected participants and controls. This detailed battery included tests to measure cognitive and motor impairment, visual and auditory recall, and attention. Additionally, all WIHS participants were given the Mental Alternations Test and Karnofsky Performance Scale for eight of their initial visits from 1994 to 1998. Noting the increasing incidence of HIV infection among adults aged 50 years and older, as well as the trend of survival among HIV-infected persons, the WIHS began evaluating the effects of aging on the cohort during WIHS III. A screening battery of the Trail Making and Symbol Digit Modalities Tasks was implemented at regular intervals. Participants from both enrollment waves still attending WIHS visits in 2004 and 2005 also completed screening tests to assess reading level, quality of education, and pre-morbid intelligence. These scores will be valuable in adjusting analyses for the effects of culture, linguistics, and differing educational experience, as well as providing more accurate indices of cognitive reserve as measured by reading level and IQ. To accommodate this rapid expansion of neurocognitive research, the WIHS recruited Drs. 
Crystal, Kreek, and Manly. Drs. Crystal and Kreek subsequently applied for and received RO1 funding for two new substudies to characterize the intersection of specific genetic markers, cognitive performance, and psychiatric illness, especially substance abuse, in the WIHS. 
• Measures of physical functioning. In addition to improving measures of mental health and neurocognition, WIHS has expanded the assessment of physical health. In general medicine and geriatrics, the last decade has seen an expansion of the association of impairments in specific physical functions, such as muscle strength and balance, with the development of disability. Traditionally, disability is defined as age-associated physical disability within two domains, (1) basic self care activities known as activities of daily living (ADL) and (2) instrumental activities of daily living (IADL)334, 335. More modern approaches have characterized frailty, a physiologic state of increased vulnerability to stressors, which is an aggregate expression of risk resulting from age- or disease-associated physiologic accumulation of subthreshold decrements of multiple physiologic systems. Although early stages of this process may be clinically silent, it is thought that substantial vulnerability to deterioration in physical health may occur when the losses of reserve reach an aggregate threshold. The WIHS has partnered with Dr. Linda Fried at Johns Hopkins in developing ADL, IADL, performance-based, and frailty measures. Data collected during WIHS 
III are important cross-sectional assessments and will be extremely powerful with further follow up in WIHS IV.