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Nat. Med., Jan 03 2025, | https://doi.org/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
M. Ali Rai1, Jana Blazkova1, Lela Kardava1, Jesse S. Justement1, Victoria Shi1, Maegan R. Manning1, Aniqa Shahid2,3, Winnie Dong3, Brooke D. Kennedy1, Adeline B. Sewack1, Jeanette Higgins4, Clarisa M. Buckner1, Kathleen Gittens5, Raymond E. West III6, Aaron S. Devanathan6, Ralph Mangusan7, Kathryn Lurain7, Ramya Ramaswami7, Robert Yarchoan7, Michael C. Sneller1, Alice K. Pau8, Zabrina L. Brumme2,3, Susan Moir1 & Tae-Wook Chun1
1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
2Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
3British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
4Leidos Biomedical Research, Frederick, MD, USA.
5Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
6Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
7HIV and AIDS Malignancy Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
8Division of Clinical Research, NIAID, NIH, Bethesda, MD, USA.
Corresponding author
Correspondence to Tae-Wook Chun.
1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
2Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
3British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
4Leidos Biomedical Research, Frederick, MD, USA.
5Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, USA.
6Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
7HIV and AIDS Malignancy Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
8Division of Clinical Research, NIAID, NIH, Bethesda, MD, USA.
Corresponding author
Correspondence to Tae-Wook Chun.
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.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-01-22)
- 국외 연구진
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