Background: Solid organ transplantation in HIV⁺ patients (pts) is complicated by the interactions between antiviral therapy (ARV) and immunosuppressive agents, e.g., cyclosporine (CsA). High drug levels could result in increased toxicity; low levels could result in organ rejection or HIV viral breakthrough. Pharmacokinetic (PK) studies were done to evaluate CsA-ARV interactions.

Methods: PK studies were obtained in 17 HIV⁺ liver and kidney transplant subjects pretransplant (pretx), and during weeks 1–2, 4–8, 12, 28, and 52 and yr 2 post-transplant. All subjects were on protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) or both; CsA was added post-transplant. All drugs were measured by LC/MS. AUC was measured from one dosing interval to another for each drug (8–24 hrs). AUC and dose data from published studies or the manufacturer were used for comparisons (“literature”).

Results: Pretx PI AUCs tended to be ~20% below the literature mean AUC for each PI measured (indinavir, nelfinavir, saquinavir), and decreased further during the first 12 weeks post-transplantation, before returning to pretx values. The exception was lopinavir/ritonavir (LPV/RTV) AUCs, which were 5–6 times higher than the literature mean for LPV AUC, and up to 3 times higher than that for RTV pretx through week 12. NNRTI (efavirenz, nevirapine) AUCs were generally near the literature mean AUC both pre- and post­-transplant. CsA AUCs were generally lower for pts on any ARV compared to CsA AUCs in nonHIV transplant pts, especially in the first few weeks after transplantation. Over time, for pts on PIs, the CsA dose had to be decreased by more than 75% to maintain CsA AUCs within range, while CsA dose and AUCs remained essentially unchanged for pts on NNRTIs. Despite the decreasing dose of CsA for those on PIs, the amount of CsA delivered, when adjusted for dose and body weight, was at least twice that for NNRTIs, due to progressive increases in intestinal CsA bioavailability.

Conclusions: Use of PIs in HIV⁺ transplant pts markedly increases CsA AUC, requiring progressive dose reduction. PI values may be low at baseline, and addition of CsA post-transplant may further lower PI levels, although this effect seems to diminish over time. Little interaction between CsA and NNRTIs were observed.