HIV-associated neurocognitive disorders (HANDs) remain common despite combined antiretroviral therapy (cART). Estimates of the prevalence in virologically suppressed people living with HIV range from 25% to 40% [1,2] and asymptomatic neurocognitive impairment accounts for up to 70% of all forms of HAND . Diagnosis is becoming more difficult as people living with HIV have an increasing burden of comorbidities, including aging-related disorders [4,5] cardiovascular and cerebrovascular diseases , metabolic disorder, insulin resistance and diabetes mellitus , polypharmacy, and coinfections. Particularly important in certain countries are substance use disorders (SUDs). It is clear from both basic science and epidemiological studies that SUDs may increase the risk of HAND [8,9]. It is also clear that there is substantial overlap in the neuropsychological profiles of cognitive impairment attributable to HIV and SUDs. However, the extent to which the neuropsychological profiles overlap requires further evaluation. A common clinical problem is whether a patient has cognitive impairment related to HAND or SUD or some complex interaction of both, be it additive or synergistic. A means of distinguishing between the two would help clinicians immeasurably, and potentially guide therapies, both pharmacological and nonpharmacological in a more precise manner.
The article by Martin et al. in this issue is a significant step in this direction. They have capitalized on sound existing neuropathological distinguishing points: SUDs especially involve the limbic system underpinned by disturbed dopaminergic input leading to reward-driven behavior, whereas HAND is largely a subcortical or basal ganglia disease with disturbed executive function through disrupted connections. A cohort of 548 participants (458 SUD+; 162 HIV+ with half virally suppressed and three quarters taking cART; 359 males; 69 HIV−SUD−; 21 HIV+SUD−; 317 HIV−SUD+; 141 HIV+SUD+) was tested with the weather prediction task (neostriatal function assessing executive connections) and the monetary choice questionnaire (limbic system assessing reward control). HIV+ participants performed more poorly on the weather prediction task regardless of SUDs while those with SUDs were worse on the monetary choice questionnaire. The study suggests that widely available clinical tests may indeed be useful in distinguishing the likely cause of demonstrable cognitive impairment in people with HIV infection and SUDs.
The results from Martin et al. do come with some caveats. First, there may be a degree of selection bias as the study participants were paid. Nonetheless, this is a common problem in this type of research. Second, it was cross-sectional but this design is appropriate as a first step. Third, there was a relatively small number of females, an emerging issue of importance given that sex influences HAND risk [11–13]. Fourth, the extent to which even milder forms of HAND may modulate the dopamine reward system in patients with SUDs is not apparent. There is reason to expect an interaction given that HAND, at least in its more severe forms, is characterized by dopamine deficiency . Fifth, as the authors point out, the findings are probably not applicable to patients who use methamphetamine. Lastly, the potential for some antiretroviral drugs themselves to influence the findings was not addressed though it should be remembered that the issue of antiretroviral drug neurotoxicity remains controversial.
Despite these issues, Martin et al. have advanced the field of neuro-HIV research and provided a clear path for further work. This will need to encompass prospective studies with both virally suppressed and unsuppressed patients with varying degrees of HAND along with perhaps separate studies of the effect of methamphetamine. While these more definitive studies take place, the data from Martin et al. do provide the clinician with a more granular understanding of the cognitive impairment associated with SUDs and allow consideration of these relatively simple inexpensive neuropsychological tests to aid at a clinical level in the assessment of the impact of some SUDs on cognition in people with HIV.
Conflicts of interest
There are no conflicts of interest.
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