Ugandan study suggests high rates of HIV dementia in Africa

HIV-related neurological problems could be common in Africa, according to a study published in the January 30^th issue of Neurology, which found that 24 of 78 (31%) randomly sampled patients with HIV attending an AIDS clinic in Uganda had HIV dementia. The risk of HIV dementia was highest in people who were older or who had more advanced HIV disease (CD4 cell counts below 200).

The rates of HIV dementia in the study are quite similar to what was observed in people with HIV in developed countries in the 1980s before the availability of antiretroviral medications.

If these rates are indeed representative of the risk of HIV dementia across sub-Saharan Africa (which is not yet clear), given the burden of HIV in Africa, an exceedingly large number of people with HIV could have dementia or develop dementia as their illness progresses.

“We’re looking at more than 8 million people in this region," said Dr Ned Sacktor, a Johns Hopkins neurologist and senior author of the study in Uganda.

This would put HIV dementia on par with Alzheimer’s disease and dementia caused by strokes among the most common forms of dementia in the world. However, unlike those latter conditions, HIV dementia may be treatable and even potentially reversible with antiretroviral treatment (ART) in many patients —especially provided treatment begins soon enough.

The Ugandan study

However, the Ugandan study used a battery of rigorous neuropsychological tests that had been translated into the local language (Luganda) and culturally adapted for use in that setting. In addition, 100 HIV-negative subjects from the same setting, matched for age and educational background with the HIV-positive participants, were evaluated with each of these tests in order to construct a picture of the norms in that community.

The study enrolled randomly selected adults with HIV at the Infectious Disease Clinic at Mulago Hospital, Makerere University (Kampala), and excluded anyone who was severely disabled (Karnofsky scores below 50), or who had a recognized active or known past CNS opportunistic infection, a fever >37.5 °C, a history of a chronic neurologic disorder, active psychiatric disorder, alcoholism, physical deficit (such as amputation), or severe medical illness that could interfere with taking the tests.

These subjects were then evaluated and scored (0) for no dementia, (0.5) for mild or subclinical cognitive impairment and (1) for dementia based upon whether he or she had scored significantly below the locally determined mean for their age and education group on two or more of the neuropsychological tests. In addition, to be diagnosed with dementia, subjects had to have symptoms, functional deficits or physical findings on a neurologic exam consistent with HIV dementia.

Most of the study 78 HIV-positive participants were women (69%), which is representative of the local HIV demographics. The mean age was 37 (range 18 to 63 years), and the mean education was 8.6 years (range 0 to 21 years). 22 (28%) were on or had previously taken antiretroviral medication. Of note, 31 (40%) had previously been diagnosed with syphilis (which could be significant given the fact that syphilis can cause neurological problems as well). However, the authors wrote “patients in Uganda are frequently given the diagnosis of syphilis when they develop a rash of any type.”

Despite the exclusion of severe disease, many of the HIV-positive participants had fairly advanced disease. Fifty-eight (75%) had WHO Stage 3 or 4 disease. Twenty-five (32%) had peripheral neuropathy. The mean functional score of the subjects was a Karnofsky score of 75 (range 50 to 100). CD4 cell counts were available for 70 people, the mean CD4 count was 219 cells/mm³(range 3-1002). The most common symptomatic complaints were depression (which is not specific to HIV dementia) in 50 (64%), memory problems in 46 (59%), headache in 46 (59%), and numbness in 42 (54%). Telltale motor problems such as balance problems and slowing of hand movements were reported by 32% and 27% respectively.

Background on HIV dementia

As HIV infection progresses, it can cause a range of neurological (cognitive, behavioural and motor) disorders collectively referred to as HIV dementia (although the term is sometimes reserved for more severe cases). Mild HIV neurological impairment usually begins with difficulty in concentrating and forgetfulness, but gradually patients begin to develop trouble walking (gait and balance problems), or with fine finger movements. These symptoms may increase in severity to the point where they may interfere with normal daily life and in extreme cases can lead to total disability.

In the 1980’s and early 1990’s, HIV-related neurological problems were perceived to be common in the developed world, with subtle impairment detected in up to 40%, and more severe dementia in 10-15%. However, the use of antiretrovirals (even just AZT by itself) appeared to dramatically reduce the incidence of HIV dementia (although recent studies suggest that the prevalence is again on the increase as people with HIV live longer).

In resource-limited settings, however, where there has been very little access to ART, HIV dementia has received scant attention. In an accompanying editorial, Brew and González-Scarano suggests a couple of possible explanations for this:

“In countries that have few if any neurologists, and where HIV infection often presents with an overwhelming opportunistic infection such as tuberculous or cryptococcal meningitis, it is no surprise that what can seem to be mild cognitive deficits are underrecognized or considered unimportant.”

Also, until relatively recently, neurological assessment relied on tests that had been developed primarily for use in the United States — and which were of dubious utility in African populations.

Results

The study found that 37 (47%) subjects had minor cognitive or motor disorders not yet severe enough to affect everyday functioning (most of the milder complaints could have been due to depression)

As noted above, 31 patients were ultimately diagnosed with HIV-dementia.

This was not associated with any greater frequency of syphilis diagnosis, head trauma, prior education, time since diagnosis or other factors. However, age and CD4 count were significantly associated with the diagnosis of HIV dementia by logistic regression analysis. Each additional ten years of age conferred a greater than twofold risk of HIV dementia (OR 2.06, 95% CI: 1.05 to 4.07; p

Implications

Although this study was small, its methods compared to earlier studies in this setting were far more rigorous. Even if some of these people with HIV had other neurological conditions such as CNS infections or neoplasms (which could not be assessed due to cost of neuroimaging, and other diagnostic procedures), the study's exclusion criteria should have eliminated most of these.

It is not yet clear whether these rates of dementia would be consistent across sub-Saharan Africa, as there are significant differences from one country to another in both viral subtypes and host factors that could affect susceptibility to HIV-dementia. For example, HIV-1 subtype D is prevalent in Uganda, and there are suggestions it is associated with more rapid disease progression.

According to Dr Sacktor, “large-scale testing would have to be conducted before we know the global reach of HIV dementia, but this study sends a clear message that it exists in high proportions in sub-Saharan Africa and is an under-recognized condition that needs to be studied and treated."

According to the editorial by Brew and González-Scarano, the findings could also have significant implications for HIV control in the region, since HIV-related neurocognitive impairment has been associated both with high rates of risky sex, and the failure of patients to be adherent to treatment (which in turn increases the risk of drug resistance).

“Failure to recognize cognitive impairment will not only impair individual therapy but will harm the efforts to control HIV in a community, as cognitively impaired patients are less inhibited and are more likely to engage in HIV-related risk behaviour. This may be compounded if the transmitted strains are also resistant to HAART,” they write.