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

接受抗CD4结构域1抗体和来那卡帕韦治疗的个体中,多重耐药HIV病毒持续受到抑制

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作者: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

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.

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