Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

Abstract

BACKGROUND:

Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.

METHODS:

We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter).

RESULTS:

A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy.

CONCLUSIONS:

UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

• Authors: Chang-Yi Wang, Wing-Wai Wong, Hung-Chin Tsai, Yen-Hsu Chen, Be-Sheng Kuo, Shugene Lynn, Jana Blazkova, Katherine E Clarridge, Hsiao-Wen Su, Chia-Ying Lin, Fan-Chen Tseng, Annie Lai, Fu-Hung Yang, Chen-Han Lin, William Tseng, Hsiao-Yi Lin, Connie L Finstad, Flossie Wong-Staal, Carl V Hanson, Tae-Wook Chun, Mei-June Liao
• Journal: The New England journal of medicine (N Engl J Med) Vol. 380 Issue 16 Pg. 1535-1545 (04 18 2019) ISSN: 1533-4406 [Electronic] United States
• PMID: 30995373 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Massachusetts Medical Society.

Chemical References

• Anti-Retroviral Agents
• Antibodies, Monoclonal, Humanized
• UB-421

Topics

• Adult
• Anti-Retroviral Agents (therapeutic use)
• Antibodies, Monoclonal, Humanized (adverse effects, pharmacology, therapeutic use)
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes
• Exanthema (chemically induced)
• HIV Infections (drug therapy)
• HIV-1 (isolation & purification)
• Humans
• Male
• Middle Aged
• T-Lymphocytes, Regulatory
• Viral Load
• Viremia (drug therapy)