Asymptomatic Mild HIV-associated Neurocognitive Disorder Increases Risk for Future Symptomatic Decline: A CHARTER Longitudinal Study
R Heaton1, D Franklin1, Steven Woods*1, C Marra2, D Clifford3, B Gelman4, J McArthur5, S Morgello6, A McCutchan1, I Grant1, and the CHARTER Group
1Univ of California, San Diego, US; 2Univ of Washington, Seattle, US; 3Washington Univ in St Louis, MO, US; 4Univ of Texas Med Branch at Galveston, US; 5Johns Hopkins Univ, Baltimore, MD, US; and 6Mt Sinai Sch of Med, New York, NY, US
Background: Although HIV-associated neurocognitive disorders (HAND) remain prevalent despite cART, the clinical relevance of asymptomatic neurocognitive impairment (ANI) (the most common HAND diagnosis) remains unclear. This study investigated neurocognitive decline over 18 to 42 months in a group of HIV-infected individuals with and without HAND.
Methods: Three hundred and eighty-seven CHARTER participants with 18 to 42 months of follow up (mean [SD] = 36.1 (10.0)) were selected based on being neuropsychologically normal ([NP-N]; n = 246) or having ANI (n = 84) or mild neurocognitive disorder (symptomatic NP impairment [MND]; n = 57) based on established criteria. Participants were assessed every 6 months and published, regression-based norms for change were used to generate an average summary change score across visits. Groups were compared (t test) on average summary change score and overall change status (decline, stable, improve; chi-square) at the last study visit.
Results: The groups did not differ on duration of follow up or on HIV disease or treatment characteristics at baseline, but the ANI group was more educated than the other 2 groups (p <0.0001) and more of the MND group were women (p = 0.006) and ethnic minorities (p = 0.02), and had lower estimates of premorbid intelligence (reading score, p = 0.003) than either the NP-N or ANI groups. At the last visit, both the ANI and MND groups had greater neurocognitive decline from baseline (as indicated by average summary change score) than the NP-N group (–0.11, –0.13, 0.03, respectively, p = 0.0002). There was no difference in average summary change between ANI and MND groups. At the level of individuals, ANI and MND participants were more likely to experience statistically meaningful decline than NP-N (23%, 30% vs 13%; p = 0.004), and ANI participants were less likely to improve than the NP-N group (7% vs 21%, p = 0.008).
Conclusions: It has been suggested that the ANI diagnosis is not valid, does not predict clinical outcomes, and may be a statistical artifact. Findings from this large longitudinal study demonstrate that ANI and MND are significant and comparable risk factors for incident cognitive worsening over 18 to 42 months, indicating that ANI and MND are both clinically important. The additional specific risk factors for such cognitive decline require further elucidation.