HIV infection has been a major global health problem for almost three decades. With the introduction of highly active anti-retroviral therapy in 1996, and the advent of effective prophylaxis and management of opportunistic infections, AIDS mortality has decreased markedly. In developed countries, this once fatal infection is now being treated as a chronic condition. As a result, rate of morbidity and mortality from other medical conditions leading to end-stage liver, kidney and heart disease is steadily increasing in individuals with HIV. Presence of HIV infection used to be viewed as a contraindication to transplantation for multiple reasons:,concerns for exacerbation of an already immunocompromised state by administration of additional immunosuppressants; the use of a limited supply of donor organs with unknown long-term outcomes; and, the risk of viral transmission to the surgical and medical staff. This Review examines open questions on kidney transplantation in patients infected with HIV-1 and clinical strategies that have resulted in good outcomes. It also describes the clinical concerns associated with the treatment of renal transplant recipients with HIV.
Background
Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, cyclosporine (CsA) and tacrolimus (TAC) trough levels (C0) or those drawn two hours after dosing (C2) correlate with drug exposure (AUC/dose) and outcomes. Due to ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, we investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels.
Methods
We prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with LC/MS/MS and AUC calculated using WinNonLin 9.0. Correlation analyses were run on SAS 9.2
Results
CsA concentration at C4 correlated better with AUC than C0 or C2, and TAC concentration correlated better at C0 or C2.
Conclusions
We suggest that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.
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