SAN FRANCISCO — Reflecting the global and growing threat of HIV-AIDS, neurologists who treat HIV-related neurological complications are seeking ways to improve screening methods among resource-strapped third world nations to determine the need for retroviral therapy.
Ned Sacktor, MD, Associate Professor of Neurology at Johns Hopkins School of Medicine in Baltimore, MD, told Neurology Today, that ''what we're seeing in Africa in terms of the high incidence of HIV dementia is what we saw in the US about 10 years ago, prior to the use of retroviral therapy.
“Despite the fact that neurologic complications are among the most frequent complications of HIV, very little is known about them in the developing world,” Dr. Sacktor said, “and resources are more limited.”
RAPID SCREENING TEST
Dr. Sacktor co-authored a study presented at the last AAN Annual Meeting here to test the validity of an International HIV Dementia Scale, a rapid screening test to help non-neurologists determine the need for retroviral therapy in patients with HIV living in sub-Saharan Africa.
Matthew Wong, a medical student at McMaster University in Ontario, Canada, evaluated the validity of the test with colleagues from the Academic Alliance Infectious Disease Clinic in Kampala, Uganda. The Academic Alliance consists of several US and Canadian medical schools, as well as the University of Kampala. They are setting up a large HIV treatment clinic to deliver antiretroviral treatment to several hundred people in Kampala.
“There was a previous screening test called the HIV dementia screening scale, but it required literacy,” Mr. Wong said. “Dr. Sacktor developed a simpler test with only three parts: four-word recall, motor speed (fine finger tapping), followed by a sequence of hand maneuvers (Luria test-fist, palm, cut for 10 seconds). We wanted to see how sensitive this test was in diagnosing HIV dementia against a gold standard of other neuropsychological tests. In addition, in environments where CD4 counts are not available, HIV dementia may be an indication for starting HAART (Highly Active Anti-Retroviral Therapy).”
The researchers administered the International HIV Dementia Scale as well as detailed demographic, neuropsychological, neurological, and functional assessments on 81 HIV-positive and 76 HIV-negative individuals. The HIV-positive group scored significantly lower than the HIV-negative group on the International HIV Dementia Scale, 9.9 versus 10.9 (p < 0.001).
Using a cutoff score of 10 for the International HIV Dementia Scale, its sensitivity was 80 percent, but its specificity was only 57 percent. Mr. Wong advised that patients who tested positive in the dementia screen could then be further examined for the presence of dementia. Mr. Wong said the results of the International HIV Dementia Scale correlated closely with the results of the more extensive neuropsychological testing.
SENSORY NEUROPATHY IN HIV-POSITIVE PATIENTS
A second part of the study assessed the frequency of sensory neuropathy in HIV-positive patients. Thirty-seven percent of HIV-positive patients complained of sensory symptoms, such as numbness, pain, or paresthesias in the feet. On examination, 38 percent had decreased ankle reflexes and 48 percent had decreased vibration in one or both feet.
Justin McArthur, MBBS, MPH, one of the coauthors of the study, said in a phone interview, that there were no pre-existing data at all regarding HIV peripheral neuropathy in Uganda. Dr. McArthur, an internationally recognized investigator on HIV infection, is Professor of Neurology and Vice Chairman for the Department of Neurology at Johns Hopkins University.
''We had been told that clinicians there really didn't see dementia or neuropathy, which is a very common refrain from busy physicians, not only in resource poor countries, but here as well. If you actually screen for these conditions, they are there. The prevalence is quite high, because these are largely untreated populations.
“It's really parallel to what we see here in this country,” Dr. McArthur continued.
''Dementia is not viewed as a major problem in the US, but up to 30 to 40 percent of HAART treated patients will have cognitive impairment.
“The treatment of HIV sensory neuropathy at this time is largely symptomatic with anticonvulsants and antidepressants, just as with diabetic neuropathy. There are several large trials in the US for HIV neuropathy – one, with a novel compound called prosaptide, an analgesic agent that may have regenerative properties as well – and we're doing a large multicenter trial with 32 sites in the US, funded by both the NIH and the pharmaceutical industry.”
UGANDA AS A TEST SITE
Dr. Sacktor said Uganda was chosen as a test site because HIV is not as much of a taboo subject as it is in other undeveloped countries. “It's discussed in churches and mosques. Ministers will speak about it. That's been going on for years now. Uganda has an estimated HIV prevalence of 5 percent, down from 15 percent in 1991. In youth, ages 15 to 25, the incidence has plummeted.”
Dr. McArthur added: “Uganda has approached HIV infection with a national public awareness program, called ‘ABC’ – Abstinence, Be faithful, Condom (if you can't be faithful). They teach it in schools, colleges, hospitals, and the workplace. That approach in large part has been responsible for the drop in seroprevalence in HIV. In this country, that hasn't happened on a national level, except for ‘abstinence’, and unfortunately it's not particularly successful either at a high school or college level. Australia is another example where strong public health messages have really made an impact on HIV seroprevalence.”
Mr. Wong noted that this is the first study that compares an HIV-positive to an HIV-negative cohort in the developing world. “HIV-positive dementia is probably the second most common cause of dementia worldwide,” he said. “HAART can greatly improve function, memory, and motor performance in patients with HIV dementia, but not necessarily back to normal. HIV dementia is now considered one of the potentially reversible dementias.”
Christina Marra, MD, Professor of Neurology at the University of Washington in Seattle, also studies AIDS in Africa. Commenting on the International HIV Dementia Scale, she said that when the score is above 10, there is only a 20 percent chance of having dementia. ''But if you score less than 10, you may or may not have dementia, as the specificity is only 57 percent. Consequently, further evaluations are necessary.
“I think it's probably valuable to have an easy-to-do test to use in order to be fairly confident that someone doesn't have dementia,” Dr. Marra said. ''It will decrease the number of people that need more intensive evaluations. We need simple ways of assessing the neurological complications because resources are more limited in the developing world. We also need to know that once we've diagnosed these diseases, the treatments that work here, work there.
“Most AIDS is in the developing world, and if we're going to make an impact, the numbers would say we have to do it in the developing world,” she continued. “We have a lot to learn about what's the best way to test for these disorders so we can truly identify and treat them. We also need to find ways to exclude other neurologic problems that might be confused with HIV dementia, and need to be treated differently. I think treating HIV is crucially important.”
Dr. McArthur said investigators are refining the instrument and looking at cutoff scores. “We've subsequently taken this scale to India, and it's begun to be used in a research project in Pune, India,” he said. “We haven't really compared the International HIV Dementia Scale to conventional neuropsychological measures in this country, but in populations where language is a barrier, it may have a role.”
ARTICLE IN BRIEF
✓ In Uganda, a team of US investigators spearheaded a study to evaluate a rapid screening test to help non-neurologists determine the need for retroviral therapy in patients with HIV living in sub-Saharan Africa.