Findings:
This review used a search of highly regarded online scientific databases, to identify six clinical trials examining the effect of transcranial direct current stimulation (tDCS) on neurocognitive functioning, depression, and sleep in people with HIV. Significant improvement in executive functioning was found collectively, as measured by the Stroop, Trail Making, and Dimensional Card Change Sorting Tests. In studies in which there was stimulation of the DLPFC, all measures of attention improved. Studies also demonstrated improvement in speed of processing, though results were inconsistent due to variability in measures used. Two studies included depression measures along with measures of neurocognitive functioning, while depression was the only outcome in a third study. Depression scores improved in all three studies. However, the longest follow-up period was only one month following the last treatment. All studies reported that tDCS was safe, well-tolerated and was associated with few adverse effects. 

Strengths and limitations:
The studies in this review were randomized and used a sham stimulation for the control group. The investigators who conducted participant assessments were blinded, and in one study, the technician who performed the intervention was also blinded. All clinical trials were conducted in English. Several features of the studies limit the strength of the findings and evidence for the use of tDCS in people with HIV. The small sample sizes used make it difficult to generalize findings to a larger population. The lack of a non-HIV arm leaves open the question of the effect of HIV on outcomes. The follow-up period was brief and occurred either immediately, or shortly after, the intervention. The long-term impact of tDCS therefore remains uncertain. tDCS techniques varied among the studies with regard to location of electrode placement, current intensity, session duration, and total number of treatments. Thus, comparability and repeatability of studies are limited. Similarly, different studies used different outcome measures which further compromises comparability. Lastly, the studies did not control for other factors known to affect cognitive functioning and psychiatric symptoms in people with HIV. These factors comprise age, nadir cd4 cell count, antiretroviral and psychiatric medications used by participants, past substance use, cardiovascular disease, hepatitis C, history of CNS opportunistic conditions, and educational attainment. 

Relevance:
Although a robust evidence base exists for the use of psychopharmacology and psychotherapy in the treatment of psychiatric disorders in people with HIV, there is a paucity of data on the safety and efficacy of neuromodulation. Effective treatments for HIV-associated neurocognitive disorders (HAND), of any kind, are even scarcer. The higher-than-expected prevalence of psychiatric disorders in people with HIV, and the unchanging high prevalence of HAND, despite virologic control, suggest the need for novel approaches to treating these disorders. The pathogenesis of HAND has evolved corresponding to advances in antiretroviral therapy, aging of the epidemic, and increasing medical comorbidities in people with HIV. AIDS dementia was originally classified as a “subcortical dementia,” and thought to affect mainly basal ganglia and subthalamic structures. More recently, disruptions in frontal-striatal-thalamocortical circuitry have been identified as underpinning neurocognitive impairment. This review’s focus on depression and neuropsychological domains, specifically measures of executive functioning, attention, psychomotor speed, memory, and speed of information processing, represents an important step in identifying underlying brain-based targets for therapeutic intervention. This review, with its important limitations, may serve as a guide for future research.