A systematic review of the screening accuracy of the HIV Dementia Scale and International HIV Dementia Scale.

BACKGROUND: The HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS) are brief tools that have been developed to screen for and aid diagnosis of HIV-associated dementia (HAD). They are increasingly being used in clinical practice for minor neurocognitive disorder (MND) as well as HAD, despite uncertainty about their accuracy. METHODS AND FINDINGS: A systematic review of the accuracy of the HDS and IHDS was conducted. Studies were assessed on Standards for Reporting Diagnostic Accuracy criteria. Pooled sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratios (DOR) were calculated for each scale as a test for HAD or MND. We retrieved 15 studies of the HDS, 10 of the IHDS, and 1 of both scales. Thirteen studies of the HDS were conducted in North America, and 7 of the IHDS studies were conducted in sub-Saharan Africa. Estimates of accuracy were highly heterogeneous between studies for the HDS but less so for the IHDS. Pooled DOR for the HDS was 7.52 (95% confidence interval 3.75-15.11), sensitivity and specificity for HAD were estimated at 68.1% and 77.9%, and sensitivity and specificity for MND were estimated at 42.0% and 91.2%. Pooled DOR for the IHDS was 3.49 (2.12-5.73), sensitivity and specificity for HAD were 74.3% and 54.7%, and sensitivity and specificity for MND were 64.3% and 66.0%. CONCLUSION: Both scales were low in accuracy. The literature is limited by the lack of a gold standard, and variation in estimates of accuracy is likely to be due to differences in reference standard. There is a lack of studies comparing both scales, and they have been studied in different populations, but the IHDS may be less specific than the HDS. These rapid tests are not recommended for diagnostic use, and further research is required to inform their use in asymptomatic screening

Characteristics of patients enrolled in studies of the HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS).

*<p>Sample sizes refer to the number of patients with data that were useable for meta-analysis, following discussion with study authors as necessary.</p>**<p>Participants were randomly selected from an existing cohort, in proportions approximating published prevalence of MND and HAD.</p>***<p>Participants were sampled to generate two equal groups (n = 50 each): those with symptoms of cognitive impairment and those without. The quoted prevalence of MND and HAD is based on extrapolation up to a larger sample (n = 200) receiving a symptom questionnaire.</p>****<p>The paper reported two independent samples, treated as separate studies in this review.</p><p>AAN: American Academy of Neurology; ADC: AIDS dementia complex; ART, antiretroviral therapy; HAD: HIV-associated dementia; HDS: HIV dementia scale; IHDS: international HIV dementia scale; IQR: inter-quartile range; MCMD: minor cognitive/motor disorder; MMSE, mini mental state examination; MND: minor neurocognitive disorder; NCI: neurocognitive impairment; SD: standard deviation (numbers refer to number of SD relative to normative means).</p

Search terms.

<p>These search terms were for PubMed, the primary source of citations. Searches of other data sources used modified versions of these terms.</p

Systematic review flowchart.

<p>Footnote: * Of the final 26 studies in the review, one comprised two separate populations <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061826#pone.0061826-Sacktor1" target="_blank">[10]</a>, which are treated as two different studies in all further analyses.</p

Estimates of diagnostic accuracy reported in studies in the review.

*<p>Unless stated, assessment for comprehensive clinical criteria (MSK, AAN, or Frascati) included neuropsychological evaluation of at least 5 cognitive domains.</p>**<p>Studies using ANI as the reference standard are not included in summary estimates or figures.</p>***<p>The paper reported two independent samples, treated as separate studies.</p><p>ADC: AIDS dementia complex; ANI: asymptomatic neurocognitive impairment; CI: confidence interval; HAD: HIV-associated dementia; HAND: HIV-associated neurocognitive disorder; MCMD: minor cognitive/motor disorder; MMSE: mini mental state examination; MND: minor neurocognitive disorder; MSK: Memorial Sloan-Kettering; NCI: neurocognitive impairment; NP: neuropsychological.</p

Methods of assessment, target population, and exclusion criteria in studies of the HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS).

*<p>Unless stated, assessment for comprehensive clinical criteria (MSK, AAN, or Frascati) included neuropsychological evaluation of at least 5 cognitive domains.</p>**<p>Major exclusion criteria were: A, past and/or recent drug and/or alcohol abuse; B, head trauma with loss of consciousness; C, neurological illness; D, psychiatric illness; E, systemic illness that may affect CNS function.</p>***<p>Participants were randomly selected from an existing cohort, in proportions approximating published prevalence of MND and HAD.</p>****<p>The paper reported two independent samples, treated as separate studies in this review.</p><p>AAN: American Academy of Neurology; ART: antiretroviral therapy; HAART: highly active antiretroviral therapy; HDS: HIV dementia scale; IHDS: international HIV dementia scale; MSK: Memorial Sloan-Kettering; NCI: neurocognitive impairment; NP: neuropsychological; NR: not reported.</p

Receiver-operator characteristic curve calculated from summary diagnostic odds ratio for the International HIV Dementia Scale.

<p>Blue checks indicate sensitivity and specificity estimates from individual studies, labelled by first author. Crosses labelled “Sacktor Uganda” and “Sacktor US” correspond to two separate studies published in a single paper <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061826#pone.0061826-Sacktor1" target="_blank">[10]</a>. The cross labelled “Sacktor MCN” corresponds to baseline data from a multicentre trial of minocycline for treatment of cognitive impairment <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061826#pone.0061826-Sacktor3" target="_blank">[77]</a>. The two points labelled “Meyer” are derived from the same study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061826#pone.0061826-Meyer1" target="_blank">[75]</a>; “(Frascati)” and “(MSK)” denote the reference standard in each case. Red circles indicate studies using neuropsychological (NP) test batteries or brief NP tests as the reference standard, again labelled by first author. Solid diamonds indicate predicted values based on pooled sensitivity and summary diagnostic odds ratio. A, Reference standard  =  AIDS dementia complex, HIV-associated dementia, or severe neurocognitive impairment. B, Reference standard  =  mild neurocognitive disorder, minor cognitive/motor disorder, or mild/moderate neurocognitive impairment. CI: confidence interval; DOR: diagnostic odds ratio.</p

Receiver-operator characteristic curve calculated from summary diagnostic odds ratio for the HIV Dementia Scale.

<p>Blue checks indicate sensitivity and specificity estimates from individual studies using comprehensive reference standards, labelled by first author. Red circles indicate studies using neuropsychological (NP) test batteries or brief NP tests as the reference standard, again labelled by first author. Solid diamonds indicate predicted values based on pooled sensitivity and summary diagnostic odds ratio. A, Reference standard  =  AIDS dementia complex, HIV-associated dementia, or severe impairment on NP battery. B, Reference standard  =  mild neurocognitive disorder, minor cognitive/motor disorder, or moderate impairment on NP battery. CI: confidence interval; DOR: diagnostic odds ratio.</p

Methodology and reporting of reviewed studies: A, the HIV Dementia Scale; B, International HIV Dementia Scale.

<p>Olive-green bars indicate fulfilment of study quality criteria, red bars indicate non-fulfilment, and blue bars indicate that this feature was not reported or available from correspondence with the study author. The study by Skinner et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061826#pone.0061826-Skinner1" target="_blank">[13]</a> applied both scales to the same patient sample and is represented in both graphs A and B. HAND: HIV-associated neurocognitive disorder.</p