The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir
Sarah E. Benner, … , Christine M. Durand, Aaron A.R. Tobian
Sarah E. Benner, … , Christine M. Durand, Aaron A.R. Tobian
Published November 8, 2022
Citation Information: JCI Insight. 2022;7(21):e162968. https://doi.org/10.1172/jci.insight.162968.
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Research Article AIDS/HIV

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

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.

Authors

Sarah E. Benner, Yolanda Eby, Xianming Zhu, Reinaldo E. Fernandez, Eshan U. Patel, Jessica E. Ruff, Feben Habtehyimer, Haley A. Schmidt, Charles S. Kirby, Sarah Hussain, Darin Ostrander, Niraj M. Desai, Sander Florman, Meenakshi M. Rana, Rachel Friedman-Moraco, Marcus R. Pereira, Shikha Mehta, Peter Stock, Alexander Gilbert, Michele I. Morris, Valentina Stosor, Sapna A. Mehta, Catherine B. Small, Karthik Ranganna, Carlos A.Q. Santos, Saima Aslam, Jennifer Husson, Maricar Malinis, Nahel Elias, Emily A. Blumberg, Brianna L. Doby, Allan B. Massie, Melissa L. Smith, Jonah Odim, Thomas C. Quinn, Gregory M. Laird, Robert F. Siliciano, Dorry L. Segev, Andrew D. Redd, Christine M. Durand, Aaron A.R. Tobian

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Figure 1

Longitudinal trajectories of CD4+ T cell counts per μL of blood following kidney transplant.

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Longitudinal trajectories of CD4+ T cell counts per μL of blood followin...
(A) CD4+ T cell counts were measured longitudinally from time since transplant among patients who received lymphocyte-depleting or -nondepleting treatment. Each line represents an individual, and each dot represents a time point. Blue and red lines represent the locally estimated scatter plot smoothing (LOESS) curves for lymphocyte-depleting and -nondepleting groups, respectively. Gray shaded areas represent the 95% CI of the LOESS curves. (B) Comparisons between therapy groups were further analyzed and subdivided into time bins. Each dot represents an individual analyzed within a time bin. Box plots represent the IQR. Medians are represented by horizontal lines in the boxes. The lower and upper whiskers represent 1.5 times the IQR beyond the quartiles. P values were estimated by Wilcoxon’s rank-sum test.