The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir

• Type of Material: Article
• Authors: Sarah E Benner, Johns Hopkins School of Medicine; Yolanda Eby, Johns Hopkins School of Medicine; Xianming Zhu, Johns Hopkins School of Medicine; Reinaldo E Fernandez, Johns Hopkins School of Medicine; Eshan U Patel, Johns Hopkins School of Medicine; Jessica E Ruff, Johns Hopkins School of Medicine; Feben Habtehyimer, Johns Hopkins School of Medicine; Haley A Schmidt, Johns Hopkins School of Medicine; Charles S Kirby, Johns Hopkins School of Medicine; Sarah Hussain, Johns Hopkins School of Medicine; Darin Ostrander, Johns Hopkins School of Medicine; Niraj M Desai, Johns Hopkins School of Medicine; Sander Florman, Miller Transplantation Institute; Meenakshi M Rana, Icahn School of Medicine at Mount Sinai; Rachel Friedman-Moraco, Emory University; Marcus R Pereira, Columbia University Irving Medical Center; Shikha Mehta, The University of Alabama at Birmingham; Peter Stock, University of California, San Francisco; Alexander Gilbert, Georgetown University School of Medicine; Michele I Morris, University of Miami Leonard M. Miller School of Medicine; Valentina Stosor, Northwestern University Feinberg School of Medicine; Sapna A Mehta, NYU Grossman School of Medicine; Catherine B Small, Weill Cornell Medicine; Karthik Ranganna, Drexel University; Carlos AQ Santos, Rush University Medical Center; Saima Aslam, Department of Medicine; Jennifer Husson, University of Maryland School of Medicine; Maricar Malinis, Yale School of Medicine; Nahel Elias, Harvard Medical School; Emily A Blumberg, Penn Medicine; Brianna L Doby, Positive Rhetoric LLC; Allan B Massie, NYU Grossman School of Medicine; Melissa L Smith, University of Louisville; Jonah Odim, National Institute of Allergy and Infectious Diseases (NIAID); Thomas C Quinn, Johns Hopkins School of Medicine; Gregory M Laird, Accelevir Diagnostics; Robert F Siliciano, Johns Hopkins School of Medicine; Dorry L Segev, Johns Hopkins School of Medicine; Andrew D Redd, Johns Hopkins School of Medicine; Christine M Durand, Johns Hopkins School of Medicine; Aaron AR Tobian, Johns Hopkins School of Medicine
• Language: English
• Date: 2022-11-08
• Publisher: JCI Insight.
• Publication Version: Final Published Version
• Copyright Statement: © 2022, Benner et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.162968
• Title of Journal or Parent Work: JCI Insight
• Volume: 7
• Issue: 21
• Grant/Funding Information: This work was supported by grants 1R01AI120938, U01AI134591, U01AI138897, and U24AI143502 from NIAID; grant 1R01DK131926 from the National Institute of Diabetes, Digestive and Kidney Diseases; grant 1F31DA054849 from the National Institute on Drug Abuse; and, in part, by the Division of Intramural Research, NIAID, NIH.
• Keywords: AIDS/HIV; Kidney Transplantation; Receptors, Antigen, T-Cell; HIV-1; Virus Latency; HIV Infections; Organ transplantation; Immunosuppression Therapy; Humans; Proviruses; T cells
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

Abstract

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRβ repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRβ clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.