Immunosuppression for HIV-Positive Kidney Transplant Recipient?
We have an HIV-positive patient on the waiting list for cadaveric kidney transplantation. I would appreciate knowing the immunosuppressant regimen of Dr. Thomas Starzl's group.

There are 2 approaches to managing immunosuppression in transplant patients, based on the nature of the highly active antiretroviral therapy (HAART) protocol that you are considering. Specifically, if you choose to use a protease inhibitor (PI)-based regimen, then you must be cognizant of complex cytochrome P450 drug interactions, whereas these interactions are not pronounced with a nonnucleoside reverse transcriptase inhibitor (NNRTI). We have used both in our transplant patients. Care should be taken in prescribing antiretroviral medications to continue already successful combinations used by the patient and to avoid drugs that are associated with clinical resistance in the patient, as defined by poor clinical response and/or failure to suppress HIV viral load to < 400 copies/mL. In addition, the toxicities and interactions of antiretroviral agents may limit their use in the posttransplant course.

Tacrolimus (TAC)-based immunosuppression along with prednisone (as per current transplantation protocol) is used, while antilymphocyte agents and other adjunctive immunosuppressive agents are generally avoided, unless there were clear indications for their use. All patients receive HAART within 48-72 hours following transplantation. Care should be taken to modify doses of TAC based on frequent (ie, daily) TAC blood levels routinely monitored after initiation of HAART. In addition, given the complex pharmacologic interactions, combinations of TAC with other agents, such as the azole antifungals and rapamycin, should be discouraged.

In our experience, PI use has been associated with significant cytochrome P450 3A interference. TAC dosing was markedly reduced to minimize levels of TAC and resultant toxicity. The average dose of TAC was 1 mg/week. However, in 1 case, the local physician treating the HIV elected to take the patient off of HAART therapy ("drug-free holiday"). The elimination of the PI caused drastic reduction in TAC levels, precipitating moderate acute rejection. This highlights the critical nature of the complex pharmacologic interactions and the need for the transplant service and the HIV virologists to communicate before making adjustments in medications.

Using NNRTI, HIV loads also remained undetectable; however, the average TAC dose was substantially higher, at 0.1 mg/kg/day. Some centers have advocated using cyclosporine and/or mycophenolate mofetil as primary immunosuppression, due to theoretical effects of these agents against HIV replication. However, in none of our patients has control of HIV been a problem. CD4+ cell counts have remained stable, without deterioration in the posttransplant period, and no episodes of opportunistic infections.