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 antiretroviral therapy.
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 these people.
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 everyday functioning.
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 have.
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 conditions group.
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%).
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.