[Viva] Fwd: FW: CATIE News - Risks for HIV-related neurocognitive impairment before and after HAART

Mon Jan 17 13:07:47 PST 2011

---------- Forwarded message ----------
From: Ross Harvey <rossh at bcpwa.org>
Date: Mon, Jan 17, 2011 at 10:05 AM
Subject: FW: CATIE News - Risks for HIV-related neurocognitive impairment
before and after HAART
To: BCPWA Group <BCPWAGroup at bcpwa.org>

FYI

Ross Harvey

Executive Director

BC Persons With AIDS Society

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*From:* mailing at mercury.catie.ca [mailto:mailing at mercury.catie.ca]
*Sent:* January-17-11 10:03 AM
*To:* Ross Harvey
*Subject:* CATIE News - Risks for HIV-related neurocognitive impairment
before and after HAART

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

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*

*REFERENCES:*

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.
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