Objective:

We evaluated safety, antiviral, immunomodulatory and anti-inflammatory properties of aprepitant–a neurokinin 1 receptor antagonist.

Design:

Phase IB randomized, placebo-controlled, double-blinded study.

Methods:

Eighteen 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.

Results:

There 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).

Conclusion:

Aprepitant 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.