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Benzodiazepine Use Is Associated With an Increased Risk of Neurocognitive Impairment in People Living With HIV

Saloner, Rowan BSa,b; Grelotti, David J. MDa; Tyree, Griffin MDa; Sundermann, Erin E. PhDa; Ma, Qing PhDc; Letendre, Scott MDa; Heaton, Robert K. PhDa; Cherner, Mariana PhDa

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15, 2019 - Volume 82 - Issue 5 - p 475–482
doi: 10.1097/QAI.0000000000002183
Clinical Science

Objective: Despite potential for dependence and adverse neurological effects, long-term benzodiazepine (BZD) use is common among people living with HIV (PLWH). As PLWH are at risk for central nervous system dysfunction, we retrospectively examined the association between BZD use and HIV-associated neurocognitive impairment (NCI).

Methods: Three hundred six PLWH underwent comprehensive neurobehavioral evaluations. Current BZD use (BZD+) was determined through self-report. Using propensity scores, 153 BZD− individuals were matched to 153 BZD+ participants on demographics and medical comorbidities. Multiple regression models examined NCI and demographically adjusted neurocognitive T-scores as a function of BZD status, adjusting for estimated premorbid ability, current affective symptoms, and nadir CD4 count. Secondary analyses explored neurocognitive correlates of positive BZD urine toxicology screens (TOX+) and specific BZD agents.

Results: Median duration of BZD use was 24 months. Current BZD use related to higher likelihood of NCI (odds ratio = 2.13, P = 0.003) and poorer global (d = −0.28, P = 0.020), processing speed (d = −0.23, P = 0.047), and motor T-scores (d = −0.32, P = 0.008). Compared with BZD−/TOX−, BZD+/TOX+ exhibited additional decrements in executive function (d = −0.48, P = 0.013), working memory (d = −0.49, P = 0.011), and delayed recall (d = −0.41, P = 0.032). For individual agents, diazepam, lorazepam, and alprazolam were most strongly associated with NCI (odds ratios >2.31).

Discussion: BZD use may elevate risk for NCI in PLWH, potentially through diffuse neurocognitive slowing and acute compromise of recall and higher-order capacities. These effects are robust to psychosocial and HIV-specific factors and occur in comparison with a tightly matched BZD− group. Prospective and interventional studies should evaluate causal associations between NCI and BZD use and explore treatment alternatives to BZDs in PLWH.

aDepartment of Psychiatry, University of California, San Diego, CA;

bSan Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA; and

cDepartment of Pharmacy Practice, University at Buffalo, Buffalo, NY.

Correspondence to: Rowan Saloner, BS, SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, University of California, San Diego, HIV Neurobehavioral Research Program, 220 Dickinson Street, Suite B, Mail Code 8231, San Diego, CA 92103-8231 (e-mail:

Supported by the Translational Methamphetamine AIDS Research Center (TMARC) award P50DA026306, the HIV Neurobehavioral Research Center (HNRC) award P30MH062512, the California NeuroAIDS Tissue Network (CNTN) awards U01MH083506, R24MH59745, and U24MH100928, and the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study awards N01MH22005, HHSN271201000036C, and HHSN271201000030C. R.S. is supported by NIAAA award T32AA013525.

Poster to be presented at the National Academy of Neuropsychology (NAN) Annual Conference; November 14, 2019; San Diego, CA.

The authors have no conflicts of interest to disclose.

Received June 12, 2019

Accepted September 02, 2019

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