Potential role of TDM in dosing protease inhibtors in HIV-HCV co-infected patients with or without cirrhosis

Abstract number: 1733_1406

Gatti F., Pagni S., Nasta P., Boldrin C., Matti A., Loregian A., Biasi L., Puoti M., Parisi S.G., Prestini K., Palù G., Carosi G.

Objectives: to evaluate the influence of liver cirrhosis on pharmacokinetics (PK) of the main protease inhibitors (PIs) in HIV/HCV co-infected patients (pts) treated with atazanavir/ritonavir (ATV/r), fosamprenavir/r (FAPV/r) or lopinavir/r (LPV/r).

Methods: 39 HIV/HCV co-infected pts receiving ATV/r (14), LPV/r (13) and FAPV±r (12) were included.

According to liver stiffness (LS) value obtained by fibroscan® at the moment of PK determination or histological diagnosis patients were classified in 2 groups:

• NC, no cirrhosis (24) if LS < 12 kPa or Knodell fibrosis score (Kfs) 1–3;

• C, cirrhosis (15) if LS ≥ 12 kPa or Kfs 4.

PIs plasma levels (PL) were determined by High Performance Liquid Chromatography. Samples for determination of Ctrough (Ct) PL were collected before the morning or the daily dose at the steady state. Results are expressed as median (interquartiles); parametric and non parametric tests have been used for comparison of continuous variables between groups when appropriate (p < 0.05 was considered as significant).

Results: 35 pts had HIV-RNA < 50 and 4 <2500 c/mL; 29/39 pts were on TDF+3tc/FTC. According to CHILD-PUGH score 10/15 C pts were classified as A5, 2 as A6 and 3 as B7.

LS in pts taking ATV/r, LPV/r and FAPV/r was respectively 6 (5–8), 6 (4–9) and 6.3 (5.9–6.9) kPa in NC and 17 (12–22), 34 (21–50) and 53.2 (48–75) kPa in C pts.

LS of C pts on FAPV was significantly higher than LS of C pts on ATV (p = 0.0004); C pts on FAPV were taking 700 mg BID according to DHHS guidelines.

Median Ct levels were 540 (170–990) in NC and 340 (100–460) ng/mL in C pts (p = 0.3) for ATV; 3020 (1020–4910) in NC and 3250 (1490–10100) ng/mL in C pts (p = 0.6) for LPV; 1350 (1020–1740) in NC and 210 (180–420) ng/mL in C pts (p = 0.01) for FAPV. Moreover PIs Ct was above minimum target concentration for wild-type virus (as suggested by DHHS guidelines) in all pts taking ATV/r, LPV/r and FAPV/r; this concentration was reached only in 2/5 C pts taking unboosted FAPV, both with a LS < 50 kPa.

Conclusions: ATV and LPV Ct doesn't seem to be affected by liver cirrhosis, while Ct of FAPV was found significantly lower in C with respect to NC pts. Of note C pts on FAPV had a median LS significantly higher than others C pts and this may cause a reduction and/or diversion of the liver blood flow related to initial portal hypertension: dosing FAPV in C pts with a very high LS (>50 kPa) may therefore require TDM.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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