SEATTLE – HIV-positive patients who have asymptomatic neurocognitive impairment may require especially close follow-up because of a sharply elevated risk of progression to symptomatic disease, according to an analysis from the CHARTER longitudinal cohort study.
At baseline, 35% of the 347 patients studied had neurocognitive impairments on testing but did not have any self-reported or observed declines in everyday functioning, and were thus classified as having asymptomatic neurocognitive impairment (ANI).
After a median follow-up of nearly 4 years, these patients had a 2.2- to 5.3-fold higher risk of developing symptomatic HIV-associated neurocognitive disorder relative to their counterparts who were neurocognitively normal, Dr. Igor Grant reported at the Conference on Retroviruses and Opportunistic Infections.
"The CHARTER study suggests that people with ANI do tend to progress to symptomatic status more frequently than people who don’t have any cognitive impairment," he commented. "ANI could be a harbinger for some underlying process that is worthy of monitoring."
In additional findings, certain other groups of patients defined by sociodemographic and HIV-related factors – women, substance abusers, and those with lower nadir CD4 counts, for example – also had an elevated risk of progression to the point of having symptoms.
Session attendee Dr. Lewis Haddow from the University College London wondered about the blinding of patients to their impairment on testing. "Could those with a label of ANI perhaps have overreported things on the self-report scale and subsequent follow-up?" he asked.
"They were not told their results, so those with ANI would not know it," replied Dr. Grant, who is professor and executive vice chair of the department of psychiatry at the University of California, San Diego.
Giving some study background, he noted that frank dementia in HIV-positive patients is uncommon today with effective antiretroviral therapy, but milder forms of impairment are still observed. "There has been concern among investigators as to whether particularly this entity of asymptomatic neurocognitive impairment, A, is real; and B, has clinical significance or any kind of predictive validity," he commented.
The CHARTER study was a multicenter study among HIV-positive patients receiving care in the era of highly active antiretroviral therapy. Every 6 months, a patient subset was assessed with a comprehensive battery of neurocognitive and other tests.
Symptomatic neurocognitive disorder was ascertained from self-report (requiring impairments on both the Patient Assessment of Own Functioning Inventory and Activities of Daily Living) and performance (requiring impairment on the Medication Management Test–Revised or on the Valpar System 3000 Work Samples and Computerized Assessment).
On average, the patients were about 43 years old and had been HIV positive for roughly a decade. Approximately 70% were on antiretroviral therapy; 82% were male, and 46% were white. With a median follow-up of 45 months, 32% developed symptomatic neurocognitive disorder.
After adjustment for education, estimated verbal IQ, and comorbidity classification, patients with ANI had an increased risk of symptomatic neurocognitive disorder based on self-report only (relative risk, 2.2; P = .005) and performance only (RR, 5.3, P less than .0001).
Certain baseline sociodemographic factors including age, female gender, low levels of education, and the presence of comorbidity as well as certain HIV-related factors including low nadir CD4 count and presence of AIDS also predicted decline to symptomatic status.
The investigators have not yet looked at the predictive performance of individual measures of neurocognitive function, according to Dr. Grant, who disclosed no relevant conflicts of interest. Also, they have not assessed virologic suppression as a predictor, but being on antiretroviral therapy did not predict decline to symptomatic neurocognitive disorder.