| Authors: Heaton R, Deutsch R, Franklin D, Woods S, Collier A,
Clifford D, Gelman B, McArthur J, Simpson D, Grant I, for the CHARTER Group |
| Abstract:Background: HIV-associated neurocognitive disorders are no immutable diagnoses and may
show highly variable clinical trajectories. Yet existing longitudinal studies of HAND typically have
fairly short followup periods (6-12 months) or have been in the context of a clinical trial, thereby
limiting our understanding of the clinical markers of incident decline and recovery.
Methods: The current study investigated the prevalence and predictors of neurocognitive
decline over 18 to 42 months in a group of HIV-infected individuals receiving care at 6
university-affiliated clinics in CHARTER. Participants received comprehensive laboratory,
neuromedical and neurobehavioral assessments every 6 months and published, regressionbased
norms for change were used to generate overall change status at each study visit.
Survival analysis was used to examine the predictors of time to neurocognitive decline over 18
to 42 months.
Results: Overall 99 (22.7%) participants experienced neurocognitive decline, 266 (61%)
remained neurocognitive stable, and 72 (16.5%) improved over 18 to 42 months. Survival
analysis revealed that younger age (relative risk (RR) = 1.28), female gender (RR = 1.75),
severe non-HIV comorbidities (RR = 2.47), being off ART (RR = 1.80), lower current CD4
counts (RR = 1.13), higher plasma (RR = 1.25) and CSF viral loads (RR = 1.26), higher AST
(RR = 1.05), lower albumin (RR = 2.01), lower hematocrit (RR = 1.63), urine toxicology positivity
(RR = 1.67), a lifetime methamphetamine diagnosis (RR = 1.84), and current major depressive
disorder (RR = 1.70) were univariable predictors of earlier neurocognitive decline (all p<.05).
Multivariable Cox regression modeling using the univariable predictors as covariates yielded a
model with Hispanic ethnicity, severe comorbidities, being off ART, and low CD4 count, in
combination, as significant predictors (total model p = .0001).
Conclusions: Neurocognitive decline is highly prevalent in HIV infection and is independently
predicted by baseline neurological comorbidities, immunocompromise, and being off ART.
Findings suggest that prospective studies regarding the possible neuroprotective benefits of
proactive ART and effective management of co-occurring CNS conditions for improving
neurocognitive outcomes are warranted. |