Abstract Background HIV-ASSIST is an online, clinical decision support tool that helps HIV clinicians select antiretroviral (ARV) regimens for patients with HIV by accounting for individual patient characteristics. Concordance between HIV-ASSIST recommendations and expert opinion has been reported to be as high as 89% in treatment-experienced patients. We evaluated the utility of the HIV-ASSIST tool for a heavily treatment-experienced, complex patient population at the University of California, San Diego (UCSD) by comparing regimens recommended by HIV-ASSIST with regimens recommended by HIV experts. Methods We identified 14 patients through a routine HIV drug resistance teaching conference at our clinic. Each case was reviewed by 5 HIV clinical experts who independently recommended an ARV regimen. A consensus “best” regimen was agreed upon among the 5 experts for each patient. Consensus regimens were compared for concordance to the top 5 regimens recommended by the HIV-ASSIST tool. HIV-ASSIST regimens were also reviewed to determine if any were high or moderate risk for virologic failure due to patient or resistance characteristics, or drug-drug interactions (DDIs). Results The patients analyzed were medically and psychosocially complex, with a high rate of multi-class resistance (Table 1). Expert-recommended regimens were concordant with one of the top five regimens recommended by the HIV-ASSIST tool for 4/14 (28%) patients (Table 2). We further classified 20/70 (29%) regimens as high risk for virologic failure and 12/70 (17%) regimens as moderate risk for virologic failure (Figure 1). Table 2.Expert-recommended consensus regimens compared to the top 5 HIV-ASSIST regimens for 14 patients with HIV and a history of drug resistance, multimorbidity, and polypharmacy.Figure 1Classification of HIV-ASSIST regimens by HIV clinical experts as either acceptable, moderate risk or high risk for virologic failure. Conclusion Compared to prior reports, we found lower concordance between ART regimens recommended by HIV experts vs those recommended by the HIV-ASSIST tool in patients with HIV drug-resistance and/or complex comorbidities and potential DDIs. Moreover, several HIV-ASSIST regimens were considered at risk for virologic failure. We recommend caution in using the HIV-ASSIST tool for complex patients with significant drug resistance. Disclosures Lucas Hill, PharmD, AAHIVP, Gilead Sciences: Speakers Bureau.