Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption.
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Bar Katharine J, Sneller Michael C, Harrison Linda J, Justement J Shawn, Overton Edgar T, Petrone Mary E, Salantes D Brenda, Seamon Catherine A, Scheinfeld Benjamin, Kwan Richard W, Learn Gerald H, Proschan Michael A, Kreider Edward F, Blazkova Jana, Bardsley Mark, Refsland Eric W, Messer Michael, Clarridge Katherine E, Tustin Nancy B, Madden Patrick J, Oden KaSaundra, O'Dell Sijy J, Jarocki Bernadette, Shiakolas Andrea R, Tressler Randall L, Doria-Rose Nicole A, Bailer Robert T, Ledgerwood Julie E, Capparelli Edmund V, Lynch Rebecca M, Graham Barney S, Moir Susan, Koup Richard A, Mascola John R, Hoxie James A, Fauci Anthony S, Tebas Pablo, Chun Tae-Wook
Аннотация
METHODS: We conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART.
RESULTS: A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 μg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P=0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus.
CONCLUSIONS: VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326 .).