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HIV dementia is common in a sub-Saharan African HIV clinic
  "HIV-related dementia can be treatable"
Karl B. Hille, The Baltimore Examiner
Jan 30, 2007
BALTIMORE - A Johns Hopkins study suggests HIV dementia rates challenge Alzheimer's and stroke dementia worldwide, but effects can be reversible.
HIV-affected white blood cells can migrate from the blood stream into the brain and cause swelling and neural damage, said Ned Sacktor, M.D., a Johns Hopkins neurologist and senior author of the article published in Neurology on Monday.
Unlike Alzheimer's and stroke-induced dementia, HIV dementia is treatable and potentially reversible with the same antiretroviral medication used to treat the infection, Sacktor said. Treatment can even restore completely normal cognitive function to some of those affected.
"Some patients do very well and get back to near-normal performance. Some patients still have mild cognitive defects," he said.
The international study led by Johns Hopkins suggested the rate of HIV-associated dementia is so high in sub-Saharan Africa it tops Alzheimer's disease and dementia from strokes. Researchers found 31 percent of a small but presumably representative group of HIV-positive patients in Uganda had HIV dementia.
HIV dementia includes memory, learning, behavioral and motor disabilities that interfere with normal daily life and in extreme cases lead to total disability, according to their article.
Though American HIV patients generally get better treatment, 10 percent to 15 percent do develop dementia, Sacktor said.
"We see it quite commonly here, but not in the same proportion we see in Uganda," he said adding it "is an under-recognized condition that needs to be studied and treated."
Of the estimated 40 million worldwide living with HIV, about 27 million live in sub-Saharan Africa, according to a release from Hopkins.
"If the rate we saw in our study translates across sub-Saharan Africa, we're looking at more than 8,000,000 people in this region with HIV dementia," Sacktor's article reports.
Before antiretroviral medications were available in the United States, the U.S. rate of HIV dementia was similar to what was discovered in this study, he said. Only 20 percent of people infected with HIV in the world are getting treatment.
Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan Africa
NEUROLOGY Jan 30, 2007;68:350-355
M. H. Wong, MD, K. Robertson, PhD, N. Nakasujja, MB, ChB, R. Skolasky, MA, S. Musisi, MB, ChB, E. Katabira, MB, ChB, J. C. McArthur, MBBS, A. Ronald, MD and N. Sacktor, MD
From the School of Medicine (M.H.W.), McMaster University, Hamilton, Ontario, Canada; Department of Neurology (K.R.), University of North Carolina School of Medicine, Chapel Hill, NC; Departments of Neurology (N.S., J.C.M.) and Orthopedics (R.S.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine (N.N., S.M., E.K.), Makerere University, Kampala, Uganda; and the Department of Medicine (A.R.), University of Manitoba, Winnipeg, MB, Canada.
Wong et al. assessed 78 Ugandan HIV+ subjects for HIV dementia. Neuropsychological test results for the HIV+ subjects were compared against normative values from 100 Ugandan HIV- subjects. HIV dementia was found in 31% (24 of 78) of HIV+ subjects.
Objective: To measure the frequency and associated risk factors of HIV dementia in an HIV clinic in Kampala, Uganda.
Methods: We systematically sampled 78 HIV-seropositive (HIV+) patients from an ambulatory HIV clinic. Participants underwent detailed sociodemographic, medical history, functional, neurologic, and neuropsychological evaluations. One hundred HIV-negative patients were recruited to provide normative data for the neuropsychological tests. A logistic regression model was constructed to determine risk factors associated with the diagnosis of HIV dementia.
Thirty-one percent (24 of 78) of the HIV+ patients had HIV dementia.
Advanced age and low CD4+ T-lymphocyte count (CD4 count) were the only variables identified as significant risk factors in the logistic regression model.

Each additional 10 years of age conferred a greater than twofold risk of HIV dementia (OR 2.06, 95% CI: 1.05 to 4.07; p < 0.05). Reduced levels of CD4 count (100 cells/μL decrement) was associated with a 60% increase in the odds of having HIV dementia (OR 1.6, 95% CI: 1.04 to 2.33; p < 0.05).
Conclusion: HIV dementia is common in HIV-seropositive Ugandan individuals attending an AIDS clinic. It is more frequently associated with patients of advanced age and decreased CD4 count.
Until recently, the relative importance of HIV dementia in sub-Saharan Africa was considered small in comparison to the burden of opportunistic infections associated with HIV. However, as access to AIDS care and highly active antiretroviral therapy (HAART) increases through programs such as the President's Emergency Plan for AIDS Relief (PEPFAR) and the United Nations' Global Fund, the incidence of opportunistic infections may decrease in the HIV-seropositive (HIV+) population.1,2 Studies in the developed world indicate that while the incidence of HIV dementia in sub-Saharan Africa may also decrease after the widespread introduction of HAART, its prevalence may increase as HIV+ patients live longer.3 This increase could create a "second epidemic" of cognitively impaired individuals in the region. These individuals with HIV dementia would have higher rates of unemployment and a decreased ability to perform their activities of daily living.4 They may also have difficulty adhering to antiretroviral medications,5 which in turn would increase their risk of viral resistance.6-8 Fortunately, HIV dementia is a treatable illness, with the majority of individuals responding to therapy.9 Studies have shown that HAART can halt the cognitive decline associated with HIV dementia and, in some cases, may reverse it.10-13
Therefore, we aimed to estimate the frequency of HIV dementia among a systematic sample of HIV+ attendees of an AIDS clinic in Kampala, Uganda. In addition, we sought to identify associated risk factors for the diagnosis of HIV dementia in this sample.
The study took place at two sites in Kampala, Uganda. HIV+ subjects were seen at the Infectious Disease Clinic (IDC) at the Mulago Hospital, Makerere University. This clinic provides care to HIV+ patients at all stages of their illness. It is partially funded by the Academic Alliance for AIDS Care and Prevention in Africa. HIV-negative (HIV-) subjects were recruited from the AIDS Information Centre (AIC) in Kampala, Uganda. The AIC provides a voluntary counseling and testing center for individuals who wish to know their HIV infection status. The AIC tests approximately 120 individuals daily, of whom approximately 80% are HIV-.
We obtained local research ethics committee approval for the study. Written informed consent was obtained for all individuals in the study. Seventy-eight HIV+ subjects were recruited from September 2003 to January 2004 using a systematic sample from attendees of the IDC. In order to be included in the study, subjects had to have a positive ELISA HIV-1 test and positive confirmatory Western blot HIV-1 test done at the IDC. HIV+ individuals were excluded if they were younger than 18 years of age, had an 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 (e.g., amputation), severe functional impairment (Karnofsky score <50) or severe medical illness that would interfere with the ability to perform the study evaluations. One hundred HIV- individuals were recruited from the client base of the AIC. The purpose of the HIV- subjects was to generate normative values for the neuropsychological tests. Applicable exclusion criteria for the HIV+ subjects were used for the HIV- subjects. HIV- subjects had a confirmed negative ELISA HIV-1 test within the past year.
Seventy-eight HIV+ subjects were assessed (tables 2 and 3). Men comprised 24 of 78 (31%) of the HIV+ subjects. The mean age of the subjects was 37 years (range 18 to 63 years), and the mean education was 8.6 years (range 0 to 21 years). Twenty-seven of 78 (35%) of the HIV+ subjects spoke English as their main language. HIV+ subjects had a mean time from the diagnosis of their HIV infection of 1,222 days (range 1 to 6,563 days). Twenty-two of 78 (28%) of the subjects had taken or were taking antiretroviral HIV medication. Thirty-one of 78 (40%) of individuals had been given a diagnosis of syphilis previously. Twenty-five of 78 (32%) of individuals had either been diagnosed with peripheral neuropathy or had symptoms and signs consistent with the diagnosis. The mean functional score of the subjects was a Karnofsky score of 75 (range 50 to 100). CD4+ T-lymphocyte counts (CD4 count) were available for 70 subjects. The mean CD4 count was 219 cells/μL (range 3 to 1,002 cells/μL).
Of the 78 patients evaluated, 24 of 78 (31%) met the criteria for mild dementia or worse, equivalent to an MSK score 1. Thirty-seven of 78 (47%) of patients had an MSK score of 0.5, representing minor cognitive-motor disorder with deficits insufficient to affect everyday functioning; 17 of 78 (22%) had an MSK score of 0 with no impairment.
Univariate analysis, as shown in tables 4 and 5, compared demographic, medical history, functional status, and immune status stratified by the three MSK subgroups (MSK score of 0, 0.5, or 1) showed significant differences in two areas. The first of these was the proportions of each group that had repeated a grade (p < 0.05), with 10 of 17 (59%) of individuals with no impairment having repeated a grade, whereas only four of 24 (17%) of individuals with mild dementia having repeated a grade. There was also significant difference in the years of education between the three groups, with the group with no impairment (MSK score of 0) having a mean education of 12 years and the group with mild dementia or worse (MSK score of 1) having a mean education of 7.3 years. Notably, there was no significant difference in the rates of peripheral neuropathy, syphilis, or use of HIV medication between the three MSK groups. Subjects with a mild or worse dementia (MSK 1) were significantly more likely to have problems with memory and balance than the groups with no impairment or subclinical impairment (table 5).
Logistic regression found that age and CD4 count were significantly associated with the diagnosis of HIV dementia (MSK score of 1). Each additional 10 years of age conferred a greater than twofold risk of HIV dementia (OR 2.06, 95% CI: 1.05 to 4.07; p < 0.05). Reduced levels of CD4 count (100 cells/μL decrement) was associated with a 60% increase in the odds of having HIV dementia (OR 1.6, 95% CI: 1.04 to 2.33; p < 0.05) (table 6).
We found that the cross-sectional frequency of HIV dementia in an ambulatory clinic in Kampala, Uganda, was 31%. Studies done in the developed world in the pre-HAART era have shown frequency rates ranging from 7.3% to 27.3% in patients with advanced infection.24-26 One of these studies used similar neuropsychological tests and criteria for the diagnosis of dementia and measured a comparable frequency of HIV dementia in a pre-HAART cohort of 27.3%.26 In sub-Saharan Africa, there have been few studies of the prevalence and incidence of HIV dementia.27-29 Most studies have used nonstandard diagnostic criteria, lacked comprehensive assessments, or were conducted in inpatient settings. Due to these limitations, it is difficult to compare results to the current findings. A more comparable study by the World Health Organization (WHO) used comprehensive neuropsychological testing to diagnose HIV dementia and estimated the frequency of dementia among individuals with systemic Stage 3 or 4 disease to be 5.9% in Kinshasa and 6.9% in Nairobi.17 However, patients in our study had lower mean CD4 counts than those in the WHO study. In addition, our patients were frequently referred to our specialized HIV clinic after hospitalization for symptomatic HIV disease, while the WHO study recruited from general medicine and infectious disease clinics and explicitly excluded patients from specialized HIV clinics. These differences in the levels of immunocompetency and patient selection may account for the disparity in the frequency of HIV dementia measured by the two studies.
The significant risk factors that we identified for HIV dementia in our study were CD4 count and the age of the subject. Studies done in the developed world have shown a similar relationship between HIV dementia status, CD4 count,30 and age.31 Interestingly, there was a trend for Luganda as primary language to be associated with HIV dementia. It is unlikely that speaking Luganda as one's primary language resulted in a disadvantage on the neuropsychological tests and thus higher measured rates of dementia in this group, as the HIV- normative group was also populated by a majority of Luganda speakers (81%, n = 81). However, in order to remove this potential confound, normative values stratified by primary language spoken might be developed for future studies. We believe that speaking Luganda is a surrogate marker for multiple factors, possibly including lower socioeconomic status, decreased access to health care, and decreased nutritional status. These factors were not measured in the current study, but inclusion of these factors in future work may determine whether they individually affect the risk of HIV dementia. Other limitations of the study were due to resource constraints such as lack of neuroimaging, lumbar punctures, and laboratory tests for confounding diseases. Through our exclusion criteria we attempted to eliminate possible confounders such as infectious meningoencephalitic disease, focal brain lesions, and active psychiatric disease as much as possible. The relatively small size of the HIV- group for the normative values for the neuropsychological tests may have led to imprecision. As a result, misclassification of HIV dementia status may have resulted in some individuals. However, it should be noted that the diagnosis of HIV dementia was not only based on neuropsychological test scores, but also the symptomatic, functional, and neurologic assessments, thereby decreasing the risk that imprecise normative values would have resulted in such a misclassification.
The demographics of the HIV+ group is representative of the population of our clinic, with a majority of the patients aged 30 to 50 and being women. We believe that the age and gender characteristics reflect the epidemic in Uganda, where the prevalence of HIV among older women aged 30 to 39 is growing despite reductions in prevalence among younger women.32 We also believe that the frequency of dementia that we observed is representative of the frequency of dementia in other urban Ugandan HIV clinics. However, population-based studies are necessary to determine whether it represents the actual prevalence of HIV dementia in the general Ugandan HIV+ population.
The self-reported rate of a previous diagnosis of syphilis in the HIV+ group was 40%. This is higher than a rate of 12% that has been noted in a cross-sectional serologic sexually transmitted infections study done in Uganda among HIV+ patients.33 This is an interesting finding, but may be due to the fact that patients in Uganda are frequently given the diagnosis of syphilis when they develop a rash of any type. Further study of syphilis in this population is warranted, as this may be another preventable risk factor for the acquisition and spread of infection, as well as CNS insult.
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