Mental and Psychological Problems Affect Over 50% in U.S. HIV Group
Slightly more than half of HIV-positive adults in a new
nationwide US study have some form of neuropsychological
(NP) impairment, which includes problems
that affect the brain (like mental sharpness and memory)
and the mood (like depression).1 People with a lowestever
(nadir) CD4 count under 200 had a higher risk of
NP impairment in this study, even if they were taking
The most severe form of NP impairment, HIV-associated
dementia, has become rarer since the arrival of triple
antiretroviral combinations. But other conditions involving
the central nervous system (HIV-associated neurocognitive
disorders, or HAND) persist.2,3 To gain a better
understanding of HAND in recent years, US researchers
organized the CHARTER study at six university HIV
clinics across the country. This report focuses on rates of
NP impairment and risk factors for NP impairment in
- How the study worked. The CHARTER study involves
1555 HIV-positive people cared for at university-associated
clinics in Baltimore, New York, San Diego, Galveston,
Seattle, and St. Louis. When people entered the
study, they had a regular medical checkup and measurement
of their CD4 count and viral load in blood. Most
CHARTER members (1205 or 77.5%) agreed to have
their viral load measured in spinal fluid. Everyone had
extensive NP testing with standard tests and psychiatric
interviews to assess people for depression and other
A single CHARTER researcher rated study participants
for conditions that can affect NP function: This
assessment placed people into three groups, those having
"incidental" conditions (which have little impact on
HIV-related NP impairment), those with "contributing"
conditions (which probably affect HIV-related NP impairment
to some degree), and those having "confounding"
conditions (which make it impossible to say whether
HIV alone is causing NP impairment). (See "Terms used
in this article.") These conditions include reading level,
history of seizures (such as epilepsy), depression, and
several substance use disorders.
Terms Used in This Article
Neuropsychological (NP) impairment: Problems that can be identified by standard tests and that are related
to mental function and mood, such as difficulty concentrating, poor memory, and depression. Also
called neurocognitive impairment.
Dementia is severe loss of brain function that may affect memory, thinking, language, judgment, and behavior.
HIV-associated dementia is the most severe form of HIV-associated neurocognitive disorder (HAND).
HAND stands for HIV-associated neurocognitive disorder (see below).
|Non-HIV conditions that may affect neuropsychological (NP) function|
Incidental: Conditions that have little impact on HIV-related NP impairment
Contributing: Conditions that probably affect HIV-related NP impairment to some degree
Confounding: Conditions that make it impossible to say whether HIV alone is causing NP impairment
|Three types of HIV-associated neurocognitive disorders|
Asymptomatic neurocognitive impairment: At least mild neuropsychological impairment that involves
two or more ability domains (on standard testing) and is not readily attributable to non-HIV conditions
explained above. People with asymptomatic neurocognitive impairment do not feel even mild negative
effects on everyday functioning.
Mild neurocognitive disorder: At least mild neuropsychological impairment that involves two or more
ability domains (on standard testing) and is not readily attributable to non-HIV conditions explained
above. People with mild neurocognitive deficit feel some mild negative effects on at least two types of
HIV-associated dementia: overall neuropsychological impairment of at least moderate severity that is not
readily attributable to the non-HIV conditions explained above. People with HIV-associated dementia
feel a major decline in at least two types of everyday functioning.
In CHARTER participants with incidental or contributing
conditions, the researchers used standard NP tests to
determine whether they had asymptomatic neurocognitive
impairment (impairment that did not interfere significantly
with everyday functioning), mild neurocognitive
disorder, or HIV-associated dementia.
Finally, the CHARTER researchers used statistical tests
to pinpoint factors that raise the risk of NP impairment
regardless of whatever other risk factors a person may
- What the study found. Age averaged 43.2 years in
the study group, and years of education averaged 12.5.
Women made up 23% of the study group, 49% of CHARTER
members were African American, 39% were non-
Hispanic white, and 9% were Hispanic. Most CHARTER
participants (58%) had been infected with HIV during
sex between men, 31% during sex between men and
women, and 28% while injecting drugs.
Almost three quarters of the study group (71%) were
taking antiretrovirals, 59% had a detectable viral load in
blood (44% of those taking antiretrovirals), and 34% had
a detectable viral load in spinal fluid (16% of those taking
antiretrovirals). Current CD4 count averaged 420, and
lowest-ever CD4 count averaged 174.
More than half of the 1555 CHARTER members (843
or 54%) had only incidental conditions that may affect
NP function, 473 (30%) had contributing conditions,
and 239 (15%) had confounding conditions that prevent
doctors from diagnosing HAND. Of the 1555 people
studied, 814 (52%) had some degree of NP impairment,
including 40% in the incidental condition group, 59% in
the contributing conditions group, and 83% in the confounding
Figure 1. In 1316 HIV-positive people
without conditions that make it impossible
to detect HIV-associated neurocognitive
disorder (HAND), 33% had impairment
detectable by testing but that did
not affect daily functioning (asymptomatic
NP impairment or ANI), 12% had
mild NP disorder (MND), and only 2%
had HIV-associated dementia (HAD).
In the 1316 people without confounding conditions,
617 (47%) had some form of HAND: 430 of those 617
(70%) had asymptomatic NP impairment, 154 had mild
NP impairment, and 31 had HIV-associated dementia.
In the whole group of 1316 people without confounding
conditions, 430 (33%) had asymptomatic NP impairment,
154 (12%) had mild NP disorder, and 32 (2%) had
HIV-associated dementia (Figure 1).
Next the researchers focused on 1066 antiretroviraltreated
people with complete data for analysis. In this
group, three factors made NP impairment more likely,
regardless of what other risk factors a person might
have: having more conditions that might affect NP function,
a lowest-ever CD4 count under 200, and the interaction
between lowest-ever CD4 count under 200 and a
detectable viral load in blood.
Then the CHARTER researchers looked at the 575 antiretroviral-
treated people who had only incidental conditions
(see "Terms used in this article"). In this group,
three factors raised the risk of NP impairment: a lowest-
ever CD4 count below 200, a detectable viral load in
blood, and the interaction between a lowest-ever CD4
count under 200 and detectable viral load in blood. The
NP impairment rate was significantly lower in antiretroviral-treated people with an undetectable viral load and
lowest-ever CD4 above 200 than in other people in this
subgroup group (30% versus 47%).
- What the results mean for you. Results of this large
and carefully planned study show that about half of people
with HIV have problems in mental function and psychology
(moods), despite the availability of antiretroviral
combinations that control HIV throughout the body.
Most people with these NP problems have impairment
that does not appear to affect their daily lives; but standard
tests can still detect that impairment. It is possible
that these problems could get worse as time goes on. A
smaller group of study participants had mild NP disorders
that did affect daily living. Only 2% had HIV-associated
dementia, the most severe form of HIV-associated
Another important finding of this study is that having
a CD4 count below 200 before treatment begins raises
the risk of NP impairment -- regardless of what other risk
factors a person may have. More than 70% of the people
in this study group had a CD4 count below 200 at some
point. The CHARTER researchers note that having such
a low CD4 count makes NP impairment more likely even
if the CD4 count climbs much higher during antiertroviral
therapy. That finding, the CHARTER team says,
raises a question about whether antiretroviral therapy
should start earlier for everyone and whether doctors
should stop relying on a falling CD4 count as a "trigger"
to start treatment.
Having a detectable viral load in blood also raised the
risk of NP impairment in this study. This finding suggests
that an effective antiretroviral combination offers
some protection against NP impairment.
Sometimes a person can tell easily whether he or she
has mental problems like forgetting frequently or mood
problems like deep depression. But it can be hard to detect
such problems in yourself when those problems are
in early stages -- or even sometimes in later stages. For
example, a person with depression may be overly critical
of himself and make problems seem worse than they are.
Another person who does have serious mental problems
may be avoiding mentally challenging situations -- without
realizing she's doing so. Therefore, people with HIV
should talk openly with their doctors and counselors
about any mental or mood problems they think they
may have. Depression, anxiety, and forgetfulness are not
signs of weakness: they are illnesses that can often be
relieved by treatment. Testing by an HIV specialist who
works in this area can identify these problems and determine
how serious they are.
- 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;75:2087-2096.
- Giancola ML, Lorenzini P, Balestra P, et al. Neuroactive antiretroviral drugs do not influence neurocognitive performance in
less advanced HIV-infected patients responding to highly active antiretroviral therapy. J Acquir Immune Defic Syndr.
- Tozzi V, Balestra P, Bellagamba R, et al. Persistence of neuropsychologic deficits despite long-term highly active
antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors.
J Acquir Immune Defic Syndr. 2007;45:174-182.
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