People who had a low CD4 cell count
in the past remain at greater risk for HIV-related neurocognitive impairment even
after they start antiretroviral therapy and their immune status improves,
participants heard in a late-breaker presentation at the Eighteenth
International AIDS Conference last week in Vienna.
Neurocognitive problems among people
– ranging from mild impairment that can only be detected with
specialised tests to debilitating AIDS dementia
– remain common in the era of
effective antiretroviral treatment.
Investigators with the CHARTER (CNS
HIV Antiretroviral Therapy Effects Research) study team assessed factors
related to HIV-associated neurocognitive problems amongst more than 1500
participants evaluated at six university medical centres in the US.
Study participants underwent
comprehensive, standardised neuropsychological assessments covering seven
cognitive 'domains', or functional areas, as well as physical and neurological
examinations. Researchers also looked at co-existing conditions and HIV-related
measures including present and past CD4 cell count, obtained through medical
records or self-report.
As reported by Igor Grant from the University of California
at San Diego,
approximately half of CHARTER participants were found to have some degree of
What's more, the investigators saw a
consistent relationship between lowest-ever past CD4 cell count -- known as the
'nadir' -- and presence of impairment. Initial analysis showed that lower CD4
cell nadirs were strongly associated with neurocognitive impairment. This
relationship remained statistically significant in an adjusted analysis taking
into account a variety of demographic and clinical factors.
Amongst people whose CD4 count had
ever dropped as low as 50 cells/mm3, approximately 60% showed some
degree of impairment. But even amongst people with well-preserved immune
function whose CD4 count had always remained above 350 cells/mm3 the likelihood stood at about 50%.
Current CD4 cell count, however, was
not found be to a significant predictor of neurocognitive impairment.
Researchers then looked specifically
at a subset of CHARTER participants who were on antiretroviral therapy and
currently had undetectable viral load. Even within this group with currently
well-controlled HIV disease, lowest-ever CD4 cell count was still a significant
predictor of neurocognitive problems.
In response to a question from the
audience, Grant said that whether an individual used antiretroviral drugs that
were able to penetrate the blood-brain barrier to enter the central nervous
system had only a "modest" effect.
These results led the CHARTER
investigators to conclude, "HIV-associated neurocognitive disorders
persist in many patients despite good immune recovery on [antiretroviral
As to the implications of these
findings, they said having ever had a low CD4 cell count may represent a
'legacy event' that has ongoing repercussions, including HIV-related brain
injury and neurocognitive impairment that might not be fully reversible even
with effective treatment later on.
Therefore, they suggested, preventing severe
immunosuppression by starting treatment earlier "may lead to more
favourable neurocognitive outcomes" in people with HIV.