Neurocognitive impairment linked to prior low CD4 cell count, even if on current suppressive HIV treatment

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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 with HIV – 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.


statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 


Relating to the brain or central nervous system.


Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.


Loss of the ability to process, learn, and remember information. Potential causes include alcohol or drug abuse, depression, anxiety, vascular cognitive impairment, Alzheimer’s disease and HIV-associated neurocognitive disorder (HAND). 

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

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 cognitive impairment.

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/mm 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 therapy]".

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.

Further information

View the abstract for this study on the official conference website.


Ellis R et al. CD4 is a predictor of HIV neurocognitive impairment (NCI) in the era of combination antiretroviral therapy (cART): results from the CHARTER study. Eighteenth International AIDS Conference, Vienna, abstract THLBB109.