 |
|
|
| |
Half in US HIV Group Have Neurocognitive
Impairment, Which Improves With NNRTIs
|
| |
| |
5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
Just over half of 1555 HIV-infected people in the US CHARTER cohort had some type of neurocognitive impairment, according to an analysis based on twice-yearly evaluations [1]. Almost one quarter of the cohort had mild impairment, and more than one quarter had moderate impairment. Taking an antiretroviral regimen that includes a nonnucleoside (NNRTI) correlated with improving impairment over time.
CHARTER includes HIV-infected people who may or may not be taking antiretrovirals. This analysis assessed neurocognitive impairment and related factors in three groups:
· 843 people with incidental comorbidity (meaning a condition that could have a minor impact on neuropsychological test results but probably does not cause even mild overall impairment)
· 473 people with contributing comorbidity (meaning a condition that could have at least a mild effect on neuropsychological test results but by itself probably does not cause the observed degree of neuropsychological impairment)
· 239 people with confounded comorbidity (meaning a condition that probably has major effects on neuropsychological test results and significantly impairs neurocognitive function while causing functional disability, or a condition that invalidates neuropsychological test results because of poor effort in taking the test)
Examples of comorbid conditions are other infections, drug abuse, and head injury.
Age and current CD4 count were similar in these three groups, but nadir (lowest-ever) CD4 was highest in the incidental comorbidity group (216), followed by the contributing group (204), and the confounded group (182). People in the incidental group had more education and better reading skills than cohort members in the other groups.
About three quarters of cohort members agreed to lumbar puncture to measure cerebrospinal fluid (CSF) load. Blood plasma and CSF loads were similar across the three groups (2.87/2.20 log copies/mL incidental, 2.82/2.12 log contributing, 2.81/2.15 confounded). The slightly higher loads in the incidental group may reflect less current use of antiretrovirals in that group (69.9% incidental, 71.7% contributing, 74.1% confounded). The higher treatment rate in the confounded group probably at least partly reflects their more advanced HIV infection.
People with confounded comorbidity were more likely to be depressed (Beck depression inventory 16.5 confounded, 15.7 contributing, and 12.3 incidental) and less likely to be employed (13% confounded, 19.7% contributing, 33% incidental).
Standard testing determined that 21% of the cohort had mild psychological impairment, 29% had moderate impairment, and 2% had severe impairment. Moderate impairment affected substantially more people in the confounded comorbidity group (about 60%) than in the contributing group (about 40%) or the incidental group (about 20%).
Among people with a nadir CD4 count above 200 and an undetectable viral load in blood, about 30% had some degree of impairment. That rate jumped to about 45% to 50% in people with a CD4 nadir above 200 and detectable viral load and in people with a CD4 nadir under 200 and detectable or undetectable viral load.
For the entire cohort, worse neurocognitive impairment correlated with (1) a lower nadir CD4 count, (2) an AIDS diagnosis, (3) worse comorbidity severity, and (4) taking antiretrovirals (which indicated more advanced HIV infection). For the 843 people in the incidental comorbidity group, worse neurocognitive impairment correlated with (1) nadir CD4 count below 200, (2) nadir CD4 count as a function of viral load, (3) and taking antiretrovirals.
CHARTER researchers evaluated 401 cohort members four or more times. Over that span,
neurocognitive performance declined in 29%, stayed stable in 47%, and improved in 17%. (That leaves 7% unaccounted for, something the CHARTER researchers did not explain in their poster.) Among people with detectable HIV in CSF at their first evaluation, significantly more had declining neurocognitive performance than stable or improving performance (P = 0.04). People with hepatitis C virus (HCV) coinfection at their first evaluation were also more likely to have declining performance than stable or improving performance (P = 0.04). Among people taking an NNRTI regimen at their first evaluation, over 50% had improving performance, significantly more than had stable or declining performance (P = 0.03). This result may reflect the greater brain-penetrating potential of NNRTIs than protease inhibitors.
The findings add to the growing literature documenting the frequent disconnect between antiretroviral success judged by plasma loads and the persistence of neurocognitive disorders in many otherwise healthy people with HIV. The CHARTER investigators speculated that low nadir CD4 count may represent "a 'legacy' event whose neurologic consequences persist once triggered." If that speculation proves true, it would be another reason to promote prompter HIV diagnosis and treatment everywhere.
Reference
1. Heaton R, Franklin, Jr D, Clifford D, et al. Persistence and progression of HIV-associated neurocognitive impairment (NCI) in the era of combination antiretroviral therapy (CART) and the role of comorbidities: the CHARTER study. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract LBPEB05.
|
| |
|
|
|
|
|
