Beta cell replacement therapy for HIV infected patients with renal failure secondary to type 1 diabetes mellitus

G.R. Roll, R.H. Lee, A.M. Posselt, C.E. Freise, S.M. Kang, R. Hirose, S. Feng, B. Hynson, P.G. Stock
UCSF, San Francisco, USA

Objective: The approach to beta cell replacement therapy with pancreas or islet transplantation in HIV+ type 1 diabetic patients (pts) has been conservative due to concerns that aggressive immunosuppression required for transplants (txs) may exacerbate their already immunocompromised condition. We report a pilot trial of beta cell replacement therapy after kidney (IAK) and simultaneous pancreas kidney (SPK) txs in HIV+ type 1 diabetic pts with end stage renal failure.
Methods: Six HIV+ pts with CD4+ counts >200 cells/ml and undetectable HIV viral loads on a stable anti-retroviral regimen underwent SPK (n=4) or IAK (n=2). Renal function in IAK pts were stable for >5 years. One IAK pt received anti-IL25 induction. The rest of the pts received Thymoglobulin (Thymo) induction and maintenance immunotherapy with CSA or tacrolimus, mycophenolate mofetil, and prednisone. >5,000 islet equivalents/kg were infused by percutaneous portal embolization at each infusion.

Results: All 4 SPK pts had excellent function of both organs and remained independent of insulin and dialysis. Two SPK pts had biopsy proven rejection of the pancreas, and 1 pt required a second course of Thymo and subsequently developed BK infection. This resolved with immunosuppression reduction. Both IAK pts required 2 islet infusions. One remains insulin independent >3 years from tx and the other was never insulin independent. Renal function remained stable in all pts. CD4+ counts returned to baseline by 1 year following lymphodepletion.
Conclusions: Type 1 diabetic pts with well controlled HIV tolerate the intensive lymphocyte depleting induction therapy required for SPK or IAK. Although there has been 1 opportunistic infection following treatment for pancreas rejection, adequate prophylaxis against infections has been largely successful in providing protection until CD4+ counts return to baseline. Well controlled HIV+ type 1 diabetic pts with renal failure should be candidates for beta cell replacement therapy with SPK or IAK.