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Development of hepatic cytolysis after switching from enfuvirtide to raltegravir in virologically suppressed patients treated with tipranavir/ritonavir
H. Khanlou1, C. Allavena2, E. Billaud2, M. McKellar1, V. Reliquet2
1AIDS Healthcare Foundation, Medicine, Los Angeles, United States, 2University Hospital, Infectious Diseases, Nantes, France
Background: Due to enfuvirtide’s (ENF) difficult administration and injection site reaction many physicians have offered raltegravir (RAL) as an alternative option in patients fully suppressed on ENF containing regimens. We report 3 cases of acute hepatic cytolysis after switching from ENF to RAL in combination with tipranavir/ritonavir (TPV/r).
Methods: 3 male patients with a mean age of 50 years [range: 40-70] developed hepatic cytolysis after switch. No hepatic cytolysis had occurred during TPV initiation. The mean CD4-cell count before switch was 337 cells/mm3 [range: 132-544]. The regimen consisted of tenofovir-emticitabine in 2 patients and zidovudine-lamivudine-abacavir-tenofovir in one. Repeated viral hepatitis studies were negative. There was no concomitant use of any hepatotoxic medications. Liver function tests (LFTs) increased within 2-4 weeks of switch to AST x10 upper limit of normal range (xN) and ALT x40N [range: x4N-x10N for AST and x4N-x40N for ALT]. TPV through levels before and after switching were available in one pt: 46 ng/mL while on ENF and 108 ng/mL after switch to RAL (therapeutic range 10-39). In 2 patients, TPV was changed to darunavir/ritonavir with normalization of the LFTs. In one patient with lower LFT abnormalities, TPV was continued due to improvement of LFTs to x2N within 4 weeks and improved TPV level (40 ng/mL) after the switch.
Conclusions: Few data are available for pharmacokinetic (PK) interaction between RAL and TPV. A possible interaction between RAL-TPV with increase in TPV levels may be responsible for these patients LFT elevations. As RAL is readily available, such combinations should be used with caution until further PK studies of RAL-TPV are available.
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