Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10 and the hMAb combination 4E10/2F5/2G12.

Objectives: To study the safety, immunogenicity and pharmacokinetics of the human monoclonal antibody (hMAb) 4E10 alone and in combination with the hMAbs 2F5 and 2G12 in HIV-1-infected persons.

Materials And Methods: Eight healthy volunteers with > or =350 CD4 cells/mm3 and < or =100 000 HIV-1 RNA copies/mL were enrolled, seven finished the study. A single 4E10 infusion was administered on day 0, followed by three doses of the hMAb combination 4E10/2F5/2G12 on days 7, 14 and 21 (total amount 8.5 g). Safety was assessed by physical examination, blood chemistry, complete blood cell count and recording of adverse events. 4E10, 2F5 and 2G12 plasma levels were determined before and at the end of each infusion and during the 7 week follow-up.

Results: No drug-related adverse events were observed throughout the study. The median plasma concentrations immediately after the first infusion were 371, 253 and 139 microg/mL for 4E10, 2F5 and 2G12. Multiple infusions resulted in maximum plasma concentrations of 407, 294 and 210 microg/mL for 4E10, 2F5, and 2G12, respectively. The median elimination half-lives (t1/2beta) were 6.6, 3.2 and 14.1 days for 4E10, 2F5 and 2G12. A low level antibody response against 2G12 was found in two patients.

Conclusion: This Phase I trial showed that the hMAb 4E10 can be safely administered, both alone and in combination with 2F5 and 2G12 to HIV-1-infected patients.