Background:  PRO 140 is a humanized CCR5 monoclonal antibody that potently inhibits CCR5-tropic (R5) HIV-1 in vitro. Previous clinical studies established PRO 140 as a well-tolerated and potent antiretroviral agent with extended activity following a single intravenous dose. The present phase 2a study is the first to evaluate subcutaneous (SC) administration of PRO 140 in HIV-1-infected subjects.

Methods:  Entry criteria included HIV-1 RNA >5000 copies/mL, only R5 virus detectable, CD4 >300/μL, and no ART within 12 weeks. Subjects (n = 44) were randomized to 1 of 4 groups:  placebo subcutaneously on days 1, 8, and 15; weekly PRO 140 162 mg subcutaneously on days 1, 8, and 15; biweekly PRO 140 324 mg subcutaneously on days 1 and 15 and placebo on day 8; weekly PRO 140 324 mg subcutaneously on days 1, 8, and 15. Subjects were followed for a total of 58 days for safety and antiviral effects.

Results:  Baseline demographics were equally distributed across the 4 groups. Baseline log₁₀ HIV-1 RNA values and CD4 counts ranged from 3.61 to 6.68 and from 307 to 911/μL, respectively, and were similar for the 4 groups. Maximum log₁₀ changes in HIV-1 RNA are shown in the table. All doses of PRO 140 were well tolerated, with no dose-related adverse events. Administration-site reactions were absent or mild in all subjects.

Conclusions:  SC PRO 140 demonstrated potent and prolonged antiretroviral activity without significant local or systemic toxicity. The findings support further exploration of infrequent subcutaneously dosing with PRO 140 as a long-acting approach to HIV-1 therapy.