Background:  TBR‑652, a CCR5 antagonist, was well tolerated by healthy volunteers. Phase 1 studies showed the feasibility of once-daily dosing. This is the first study of TBR‑652 in HIV-1-infected patients.

Methods:  This was a double-blind, placebo-controlled, randomized (4:1 to TBR‑652), dose-escalating study to assess the antiviral activity, safety, and tolerability of TBR‑652 monotherapy given orally once daily (QD) for 10 days in HIV‑1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve, CCR5-positive patients. Ten patients/dose level received 25, 50, or 75 mg TBR‑652 or placebo. Safety was monitored by vital signs, electrocardiograms (ECG), clinical laboratory values, and recording of adverse events and summarized using descriptive statistics. HIV‑1 RNA was measured from Baseline through Day 11. Patients were monitored for changes in viral tropism.

Results:  No serious adverse events or deaths have occurred. One patient withdrew consent after a single dose of study drug due to difficulty with phlebotomy. The most commonly reported adverse events were headache, nausea, constipation, diarrhea, and sinusitis. No QTc prolongation or clinically significant ECG changes were seen. Mean log₁₀ copies/mL changes in HIV-1 after 10 days of treatment were:

Conclusions:  TBR-652 was well tolerated at all dose levels. Virologic responses showed a clear dose-response. Importantly, all patients receiving 75 mg had a viral load reduction of at least 1 log₁₀. Two additional dose levels, 100 and 150 mg QD, are being evaluated to explore the top of the dose-response curve and will be included in the results at the meeting.