Neurology -- Correspondence for Wong et al., 68 (5) 350-355

Correspondence published:

Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan Africa: Nuala M. McGrath, Graham S. Cooke (1 April 2007)

Reply from the Authors: Matthew H. Wong, Ned Sacktor (1 April 2007)

Reply from the Editorialists: Bruce J. Brew (1 April 2007)

Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan Africa 1 April 2007

Nuala M. McGrath,
LSHTM, Africa Centre for Health and Population Studies
PO Box 198, Mtubatuba 3935, South Africa,
Graham S. Cooke
Send Correspondence to journal:
Re: Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan Africa

nuala.mcgrath{at}lshtm.ac.uk Nuala M. McGrath, et al.

Both Wong et al [1] and Brew et al [2] make a strong case that HIV- associated dementia (HAD) merits more attention in sub-Saharan Africa, not only because it is treatable, but also because of HAD’s possible adverse effects on HIV treatment compliance.
Treatment guidelines vary between countries in sub-Saharan Africa, but many recommend treatment initiation not only for patients with CD4 counts under 200 cells/ul but also with WHO stage IV clinical disease (which includes HAD). [3] The overall CD4 counts quoted include patients taking treatment and might overestimate the prevalence of HAD in patients presenting with CD4 counts over 200.
It would be helpful if the authors could describe how many of their patients would have qualified for treatment on CD4 criteria and how many would require a clinical diagnosis to start treatment. Regardless of whether a diagnosis of HAD is required to start treatment, monitor progress or predict treatment outcome, the challenges of diagnosing HAD in resource-constrained settings are substantial. Wong et al [1] used a battery of neuropsychological tests and a neurological assessment to diagnose HAD. Most health care systems in sub-Saharan Africa have few clinical staff and are unlikely to be able to conduct the tests used in this study. Simple tools, drawn from the extensive battery of tests described and requiring minimal expertise to deliver, are therefore vital to screen for HAD. It would be interesting if the authors could identify which tests might be useful to be developed for a routine clinical setting.
While we agree with Brew et al [2] that there is a possibility that cognitive impairment might lead to poor treatment compliance and subsequent possible increased transmission of resistant virus, the statement that "cognitively impaired patients are less inhibited and are more likely to engage in HIV-related risk behavior" is not merited. The association between reduced inhibition and increased risky sexual behaviour has been studied mostly among gay and bisexual men in developed countries. [4] The extent to which behaviors in these select populations can be extrapolated to general African populations is unclear. However, we support the authors in highlighting this as an important area for further study.
References
1. Wong MH, Robertson K, Nakasujja N, Skolasky R, Musisi S, Katabira E et al. Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan Africa. Neurology 2007; 68:350-355.
2. Brew BJ, Gonzalez-Scarano F. HIV-associated dementia: an inconvenient truth. Neurology 2007; 68:324-325.
3. WHO. WHO Case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. 2006. Geneva, WHO. Ref Type: Report
4. Semple SJ, Zians J, Grant I, Patterson TL. Sexual compulsivity in a sample of HIV-positive methamphetamine-using gay and bisexual men. AIDS Behav 2006; 10:587-598.
Disclosure: The authors report no conflicts of interest.

Reply from the Authors 1 April 2007

Matthew H. Wong,
University of Virginia
PO Box 800394, Charlottesville, VA, 22908,
Ned Sacktor
Send Correspondence to journal:
Re: Reply from the Authors

mhw9e{at}virginia.edu Matthew H. Wong, et al.

We thank Drs. McGrath and Cooke for their interest in our article. Concerning the possible overestimation of the prevalence of HAD in individuals presenting with CD4 counts over 200, it should be noted that of the 24 patients who were diagnosed with HAD in our study, 20 had not received any anti-retroviral (ARV) therapy in the past.
Of these 20 individuals, CD4 counts were available for 16, and 6 of 16 (37.5%) had CD4 counts greater than 200. In the group of 4 patients with HAD who were receiving or had received ARV therapy, only 1 of 4 (25%) had a CD4 count greater than 200. While the numbers are small, it still appears there are a significant number of individuals who present with HAD have CD4 counts in excess of 200, and would require a clinical diagnosis to be started on ARV therapy.
Regarding the difficulty of making the diagnosis of HAD in a resource limited setting, our group has done preliminary work validating a screening tool named the International HIV Dementia Scale for this purpose. The IHDS is a simple, three-part test that includes a four-word recall, finger tapping, and the an alternating hand sequence test. It is scored out of 12, and at a cutoff score of 10, the test has a sensitivity of 80% and a specificity of 55%. [5]
The IHDS is the first step towards a simple means of making the diagnosis of HAD in health care systems where the resources are not available to perform extensive neurological and neuropsychological testing. Within our neuropsychological test battery, tests of verbal memory (WHO-UCLA Verbal Learning test trial 5 and delayed recall) and executive function (Color Trails Parts 1 and 2) were the tests most likely to demonstrate impairment.
Further studies should be performed to validate a brief, practical neuropsychological test battery for routine clinical screening of HAD in sub-Saharan Africa.
Reference
5. Sacktor NC, Wong M, Nakasujja N, et al. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS 2005 Sep 2;19(13):1367-1374.
Disclosure: The authors report no conflicts of interest

Reply from the Editorialists 1 April 2007

Bruce J. Brew,
Dept. of Neurology,
Level 4 Xavier, St Vincent’s Hospital, Victoria St., Darlinghurst, Sydney, Australia,
Send Correspondence to journal:
Re: Reply from the Editorialists

b.brew{at}unsw.edu.au Bruce J. Brew

We thank McGrath and Cooke for their comments regarding our editorial in Neurology. [2] We share their concerns regarding the difficulties of delivering neurological and psychiatric care in resource-limited areas, and we agree that there is a need for simpler tests that define impairment in such circumstances. In this regard, there are simpler cognitive tests [6] and there are simpler motor-based tests. [7] Nonetheless, there are still problems relating to normative data and availability of testing instruments.
Their comments raise an additional critical issue. There is a perception that a diagnosis of impairment cannot be made without neuropsychological evaluation. This is incorrect. Significant cognitive impairment in the form of dementia is a clinical diagnosis. Its accuracy is assisted by neuropsychological assessment but its validity is not dependent on neuropsychological evaluation. Awareness of the clinical features of the disorder (with corroboration from relatives and colleagues), followed by a careful neurological exam and exclusionary tests most importantly some form of brain imaging (where possible) are the cornerstones of diagnosis.
We also agree that the association between cognitive impairment and disinhibition has not been adequately studied, let alone proven, in African populations. Nonetheless, there are three mechanisms: through the association between cognitive impairment and psychiatric disease most particularly hypomania, through the association between cognitive impairment and drug use, and most importantly through the association with apathy, a core feature of HIV related dementia.
Apathetic patients do not take the initiative to ensure "safe" sex is practiced. It would be imprudent, in our view, not to take advantage of the lessons derived from research in developed countries while waiting for extensive further clinical studies that could take years to perform.
References
6. Carey, et al. Initial validation of a screening test battery for the detection of HIV-associated cognitive impairment, Clin Neuropsy 2004; 18: 234-248.
7. Parsons TD, Rogers S, Hall C, Robertson K. Motor based assessment of neurocognitive functioning in resource-limited international settings. J Clin Exp Neuuropsychology 2007;29:59-66.
Disclosure: The authors report no conflicts of interest.