Sustained virologic suppression of multidrug-resistant HIV in an individual treated with anti-CD4 domain 1 antibody and lenacapavir

M Ali Rai; Jana Blazkova; Lela Kardava; Jesse S Justement; Victoria Shi; Maegan R Manning; Aniqa Shahid; Winnie Dong; Brooke D Kennedy; Adeline B Sewack; Jeanette Higgins; Clarisa M Buckner; Kathleen Gittens; Raymond E West 3rd; Aaron S Devanathan; Ralph Mangusan; Kathryn Lurain; Ramya Ramaswami; Robert Yarchoan; Michael C Sneller; Alice K Pau; Zabrina L Brumme; Susan Moir; Tae-Wook Chun

doi:10.1038/s41591-024-03357-0

Sustained virologic suppression of multidrug-resistant HIV in an individual treated with anti-CD4 domain 1 antibody and lenacapavir

Nat Med. 2025 Jan 3. doi: 10.1038/s41591-024-03357-0. Online ahead of print.

Authors

M Ali Rai¹, Jana Blazkova¹, Lela Kardava¹, Jesse S Justement¹, Victoria Shi¹, Maegan R Manning¹, Aniqa Shahid^{2

3}, Winnie Dong³, Brooke D Kennedy¹, Adeline B Sewack¹, Jeanette Higgins⁴, Clarisa M Buckner¹, Kathleen Gittens⁵, Raymond E West 3rd⁶, Aaron S Devanathan⁶, Ralph Mangusan⁷, Kathryn Lurain⁷, Ramya Ramaswami⁷, Robert Yarchoan⁷, Michael C Sneller¹, Alice K Pau⁸, Zabrina L Brumme^{2

3}, Susan Moir¹, Tae-Wook Chun⁹

Affiliations

¹ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
² Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
³ British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
⁴ Leidos Biomedical Research, Frederick, MD, USA.
⁵ Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
⁶ Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
⁷ HIV and AIDS Malignancy Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
⁸ Division of Clinical Research, NIAID, NIH, Bethesda, MD, USA.
⁹ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. [email protected].

PMID: 39753965
DOI: 10.1038/s41591-024-03357-0

Abstract

The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4⁺ T cell count. A longitudinal examination of plasma HIV and infectious isolates showed no evidence of viral evolution or the emergence of UB-421- or lenacapavir-resistant viruses. The individual received three cycles of liposomal doxorubicin and five doses of anti-programmed cell death protein 1 (PD-1) monoclonal antibody pembrolizumab that resulted in improvement in KS with flattening of lesions. Our data demonstrate that combination therapy with UB-421 could provide sustained virologic suppression in people harboring MDR HIV with limited therapeutic alternatives.