• Pablo Tebas, Sergei Spitsin, Jeffrey S Barrett, Florin Tuluc, Okan Elci, James J Korelitz, Wayne Wagner, Angela Winters, Deborah Kim, Renae Catalano, Dwight L Evans, and Steven D Douglas.
• aDepartment of Medicine bDepartment of Pediatrics cDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania dThe Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania eWestat, Rockville, Maryland, USA.
• AIDS. 2015 May 15; 29 (8): 931-9.

ObjectiveWe evaluated safety, antiviral, immunomodulatory and anti-inflammatory properties of aprepitant - a neurokinin 1 receptor antagonist.DesignPhase IB randomized, placebo-controlled, double-blinded study.MethodsEighteen patients were randomized (nine to aprepitant and nine to placebo). The patients received once-daily treatment (375 mg aprepitant or placebo by oral administration) for 2 weeks and were followed off drug for 4 weeks.ResultsThere were no significant changes in the plasma viremia or CD4(+) T cells during the dosing period. Aprepitant treatment was associated with significant decreases of median within patient change in percentages of CD4(+) T cells expressing programmed death 1 (-4.8%; P = 0.04), plasma substance P (-34.0 pg/ml; P = 0.05) and soluble CD163 (-563 ng/ml; P = 0.02), with no significant changes in the placebo arm. Mean peak aprepitant plasma concentration on day 14 was 7.6 ± 3.1 μg/ml. The use of aprepitant was associated with moderate increases in total cholesterol, low-density lipoprotein and high-density lipoprotein (median change = +31 mg/dl, P = 0.01; +26 mg/dl, P = 0.02; +3 mg/dl, P = 0.02, respectively).ConclusionAprepitant was safe and well tolerated. At the dose used in this proof-of-concept phase IB study, aprepitant did not show a significant antiviral activity. Aprepitant-treated patients had decreased numbers of CD4(+) programmed death 1-positive cells and decreased plasma levels of substance P and soluble CD163, suggesting that blockade of the neurokinin 1 receptor pathway has a role in modulating monocyte activation in HIV infection. Prospective studies in virologically-suppressed individuals are warranted to evaluate the immunomodulatory properties of aprepitant. Exposures exceeding those attained in this trial are more likely to elicit clinical benefit.

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