Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, 
the primary receptor for human immunodeficiency virus type 1 (HIV-1), and 
inhibits the viral entry process. A phase lb multidose study of the safety, 
pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 
HIV-1-infected patients. Nineteen patients were randomized to receive either 10 
mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 
mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were 
assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the 
study, the patients remained off other antiretrovirals or continued a stable 
failing regimen. Treatment with ibalizumab resulted in substantial reductions in 
HIV-1 RNA levels (0.5 to 1.7 log(10)) in 20 of 22 subjects. In most patients, 
HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned 
to baseline despite continued treatment. Baseline viral isolates were 
susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging 
resistance to ibalizumab was manifested by reduced maximal percent inhibition in 
a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent 
and were susceptible to enfuvirtide in vitro. Complete coating of CD4(+) T-cell 
receptors was correlated with serum ibalizumab concentrations. There was no 
evidence of CD4(+) T-cell depletion in ibalizumab-treated patients. Ibalizumab 
was not immunogenic, and no serious drug-related adverse effects occurred. In 
conclusion, ibalizumab administered either weekly or biweekly was safe and well 
tolerated and demonstrated antiviral activity. Further studies with ibalizumab 
in combination with standard antiretroviral treatments are warranted.