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CATIE News - Risks for HIV-related neurocognitive impairment before and after HAART

2011 Jan 17 - American researchers have recently completed a major analysis comparing HIV-related neurologic disorders in the era before and after potent anti-HIV therapy (commonly called ART or HAART) became available. They link neurocognitive decline to low pre-therapy CD4+ cell counts. Their findings have implications for the timing of initial therapy for HIV infection. Specifically, starting HAART before CD4+ counts fall too low may help protect the brain from injury caused by exposure to proteins produced by HIV.

Study details

Researchers performed extensive neurologic, behavioural, medical and cognitive testing on large numbers of people before (1988 to 1995-857 participants) and after (2000 to 2007-937 participants) HAART became available. None of the participants were taking medicines known to affect neurocognitive functioning. Participants were recruited from clinics in the following cities:

  • Baltimore
  • Galveston
  • New York City
  • San Diego
  • Seattle
  • St. Louis

Key findings

The research team found that participants in the HAART era who were free from HIV-related symptoms or who had only mild symptoms of HIV disease had greater rates of neurocognitive impairment (NCI) than people of similar health status in the pre-HAART era. This result was unexpected and occurred despite these findings about participants in the HAART era:

  • More participants in the HAART era were generally free from symptoms of HIV disease than those in the time before HAART.
  • Participants in the HAART era tended to achieve suppression of HIV levels in the blood and cerebrospinal fluid unlike most participants in the pre-HAART era.
  • Very similar testing and assessments of neurologic and other aspects of health were used in both time periods.

The study team suggests that the reason for greater NCI in the present era is likely due to the fact that participants waited until they had severe immunodeficiency before initiating treatment. For instance, among symptom-free participants, the average CD4+ count when initiating therapy in the two time periods was as follows:

  • pre-HAART era - 455 cells
  • HAART era - 295 cells

Participants' lowest-ever CD4+ cell count (the nadir CD4+ count) emerged as a factor that could significantly predict a person's chances of having NCI in both time periods. Furthermore, smaller studies done in Australia, Italy and Spain have also made similar findings as the present American study.

Results-Severe neurocognitive impairment (dementia)

When researchers focused on the subset of participants with severe NCI they found some intriguing results. Overall, among participants with AIDS, the proportion with dementia was greater in the pre-HAART era (17%) than in the present era (7%).

However, among the subset of people without general symptoms of HIV disease, dementia was more common in the present era (7%) than in the past (4%). The research team proposed a potential explanation for this difference, as follows:

  • People in the HAART era are more likely to survive for prolonged periods with low CD4+ cell counts. However, longer survival with untreated HIV infection, particularly at low CD4+ counts, probably allows HIV to slowly degrade the brain through inflammation and other processes.

Key point

The lowest-ever CD4+ count was strongly linked to the risk of developing NCI in both the past and present treatment eras. According to the study team, this finding indicates that "early severe immunosuppression may initiate at least partially irreversible changes in the [brain] and that earlier treatment aimed at protecting patients from these processes may improve [neurocognitive] outcomes."

What's next?

The results of this study may influence future decision-making about the timing of HAART because letting the CD4+ count fall to low levels seems to be associated with an increased risk for HIV-related brain injury. However, despite its size, this study does have limitations because it is a cross-sectional study; that is, participants were only assessed at one point in time. Therefore, the conclusions drawn must be subject to caution. To definitively deal with the question of when to start HAART and other related issues of brain health, the study team calls for long-term clinical trials to "assess the value of initiating treatment in neurocognitively normal [HIV-positive] persons before they become markedly immunosuppressed."

-Sean R. Hosein


  1. Heaton RK, Franklin DR, Ellis RJ, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. Journal of Neurovirology . 2010 Dec 21. [Epub ahead of print].
  2. Heaton RK, Clifford DB, Franklin DR Jr., et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology . 2010 Dec 7;75(23):2087-96.


CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.

From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at


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