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Kidney Transplantation in HIV Infection

Student thesis: Doctoral ThesisDoctor of Philosophy

The prognosis of human immunodeficiency virus (HIV) has been dramatically improved over the years owing to more widespread access and earlier use of antiretroviral drug therapy. Consequently, HIV-positive patients are no longer dying from AIDS related illnesses but increasingly are experiencing non-infectious complications such as end-stage kidney disease (ESKD).

The prevalence of ESKD among 7,307 black HIV-positive patients in the UK CHIC cohort increased from 0.44% in 2000/2001 to 1.09% in 2010/2011. Kidney transplantation was increasingly used to treat ESKD. Among those suitable for transplantation, survival on dialysis and post-kidney transplantation was similar (89% and 85% at five years, respectively, p=0.53).

97 HIV-positive kidney transplant recipients were identified in the United Kingdom. Of those that met the study criteria (n=78), 34% received a kidney allograft from a living donor and the median follow-up period was 31 (19, 55) months. Patient survival at 1 and 3 years post-KT was excellent at 97·3% and 94·8%, respectively, and the corresponding graft survival rates were 97.3% and 90.0%. Delayed graft function was encountered in 16 patients (21%), all of whom had received a kidney from a deceased donor. The cumulative incidence of allograft rejection (AR) at 1 year was 58% and 21% among patients on ciclosporin (CsA) and tacrolimus (Tac) respectively. Choice of calcineurin inhibitor (CNI) was significantly associated with AR (hazard ratio for Tac vs. CsA 0.25 [95% CI 0.11, 0.57], p=0.001).

Complex drug interactions complicated post-transplant management of HIV/KT recipients. CNI doses for patients who received ritonavir-boosted protease inhibitor (PI) containing cART were significantly lower throughout the first year post-KT (30~fold for ciclosporin, 100~fold for tacrolimus) compared to those receiving PI-sparing antiretroviral regimens. By week 4 post-transplant, more than half of the patients in both CNI groups had achieved target trough concentrations i.e. 50% Tac vs 57% for CsA. Patients in whom mycophenolate (MMF) concentrations were routinely measured experienced significantly reduced cumulative incidence of latent virus infections, even after adjusting for cytomegalovirus prophylaxis (20% vs 84% respectively, p=0.0001).

In conclusion, these data presented in this thesis demonstrate the increasing burden of ESKD despite the widespread use of cART. Findings corroborate the feasibility of kidney transplantation in HIV-positive patients albeit with a high rate of delayed graft function and allograft rejection. Poor allograft outcomes may have been complicated by suboptimal immunotherapy owing to the pharmacokinetic interactions between antiretroviral and immunosuppressant drugs. The use of tacrolimus may be the preferred CNI for use in KT in HIV-positive individuals, and monitoring of mycophenolate drug concentrations may be beneficial in this patient population.
Original languageEnglish
Awarding Institution
Award date2016


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