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.
| Original language | English (US) |
|---|---|
| Article number | e162968 |
| Journal | JCI Insight |
| Volume | 7 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 8 2022 |
Funding
SEB, DO, NMD, SF, MMR, RFM, MRP, SM, PS, AG, MIM, VS, SAM, CBS, KR, CAQS, SA, JH, MM, NE, EAB, BLD, ABM, MLS, CMD were responsible for data acquisition. SEB was responsible for the first draft of the manuscript. SEB, MLS, JO, TCQ, GML, RFS, DLS, ADR, CMD, AART were responsible for design of this study. SEB, XZ, EUP, RFS, CMD, ADR, AART were responsible for interpretation of the data. XZ, EUP and SH were responsible for data analysis. Administrative and logistical support was supported by YE, REF and JO. Laboratory testing procedures were provided by YE, REF, JER, FH, HAS and CSK. All authors reviewed, edited and approved the final manuscript. A special thank you to the organ donors, families, and recipients who made this study possible. We also thank the HOPE in Action team for their hard work and assistance with this project. We would like to thank the Johns Hopkins FEST and TCR Immunogenomics Core and the Genomics Laboratory at the Frederick National Laboratory for Cancer Research for performing the TCRβ sequencing using Adaptive Biotech kits. We thank Thomas Bello from Adaptive Biotechnologies for assistance with TCRβ sequencing analysis. This research was performed as a project within the HOPE in ACTION clinical trial network, a collaborative clinical research project funded by National Institute of Allergy and Infectious Diseases (NIAID). 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.
ASJC Scopus subject areas
- General Medicine
