Impact of immunosuppressive therapies on HIV persistence during kidney transplantation

P. Stock1, B. Barin2, H. Hatano1, R. Rogers1, M. Roland1, T.-H. Lee3, M. Busch3, S. Deeks1, Solid Organ Transplantation in HIV Study Investigators

Background: Chronic inflammation may contribute to HIV persistence through a number of potential pathways. We explored the impact of immunosuppressant therapy on peripheral blood measures of HIV persistence following kidney transplantation. We were particularly interested in the relative effect of sirolimus (rapamycin) as this drug inhibits T cell proliferation and reduces CCR5 expression.
Methods: Stored plasma and PBMC aliquots prior to transplantation and at weeks 12, 26, 52 and 104 post-transplant were obtained from a prospective cohort. Eligible subjects had CD4 cell count >200 and an undetectable HIV RNA level pre-transplant. Ultrasensitive measures of plasma- and cell-associated RNA levels were measured using a modification of the TMA assay. Data after any confirmed virologic failure (HIV RNA > 200 copies/mL) were censored. Predictors of HIV persistence (which included CD4 cell count and exposure to various immunosuppressive drugs as time-dependent covariates) were examined via linear repeated measures models.
Results: HIV persistence was measured in 91 kidney recipients. The median post-transplant follow-up was 3.5 years [IQR 2.7-4.6]. Immunosuppressive drugs used at week 12 included cyclosporine (21%), tacrolimus (74%), sirolimus (9%), mycophenolate mofetil (73%) and prednisone (76%). In the multivariate model, higher baseline HIV RNA level (p< .0001), white race (p=0.01), and a longer duration of follow-up post-transplant (p=0.09) were associated with higher post-transplant plasma HIV RNA levels. A higher baseline HIV DNA (p< .0001) was significantly associated with higher HIV DNA levels post-transplant, while higher CD4 count (p=0.001), sirolimus use (p=0.04) and a longer duration of follow-up (p=0.06) were associated with lower post-transplant HIV DNA levels.
Conclusions: Among individuals maintaining effective viral suppression post-kidney transplantation, there was trend toward higher plasma HIV RNA levels and lower HIV DNA levels over time. Exposure to sirolimus may be associated with relative reductions in HIV DNA levels. Future studies focused on this drug are warranted.

19th International AIDS Conference
Abstract no. THPE099

Suggested Citation
"P.Stock, et al. Impact of immunosuppressive therapies on HIV persistence during kidney transplantation. : 19th International AIDS Conference: Abstract no. THPE099 "