NEW YORK (Reuters Health) - In a phase I study, a single infusion of TNX-355, a novel anti-CD4 monoclonal antibody (MAb), reduced plasma HIV levels for up to 21 days. Results of this “proof-of-concept study demonstrate the feasibility of inhibiting HIV-1 in vivo by a CD4-specific MAb and suggest that TNX-355 is a promising new candidate for the treatment of HIV-1 infection,” the investigators say.
TNX-355, Dr. Daniel R. Kuritzkes from Brigham and Women’s Hospital in Boston and colleagues explain in the January 15th issue of The Journal of Infectious Diseases, is a humanized IgG4 MAb that binds to extracellular CD4 to block the attachment of HIV-1 to cells.
They evaluated the safety and antiretroviral activity of single infusions of TNX-355 in 5 sequential cohorts, each consisting of 6 HIV-1-infected patients with uncontrolled viral replication.
The researchers observed a dose-dependent increase in CD4+ T cells within 24 hours of infusing TNX-355. They also saw a dose-related reduction in plasma HIV-1 RNA levels that correlated with complete CD4+ cell coating by TNX-355.
With the 3.0, 10, and 25 mg/kg doses, the respective peak median reductions in plasma viremia were 0.56, 1.33, and 1.11 log copies/mL -- which occurred on days 4-7, 14, and 21.
“A MAb that suppresses HIV-1 replication for 2-3 weeks after administration could offer significant clinical benefits in the treatment of drug-resistant HIV-1 infection,” Dr. Kuritzkes and colleagues write. Combined use with other HIV-1 entry blockers could have “potent synergistic” inhibitory effects on HIV-1 replication, they add.
TNX-355 was well tolerated. There was no evidence of TNX-355-related immunosuppression or inappropriate immune activation. Also, no anti-TNX-355 antibodies were detected, “which suggests that the immunogenicity observed in macaques might be avoided in humans,” the investigators say.
In comments to Reuters Health, Dr. Kuritzkes said, “these results show that TNX-355 has anti-HIV activity in HIV-infected human subjects, and that further study is warranted.”
A phase II study is currently being planned.
Source: J Infect Dis 2004;189:285-291. [ Google search on this article ]
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