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FW: NATAP/Glasgow: NNRTI levels Increased in HIV+ Cirrhotics

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  • alleypat@comcast.net
    NATAP http://natap.org/ _______________________________________________ Nonnucleoside Levels High in HIV-Infected Cirrhotics 8th International Congress on Drug
    Message 1 of 1 , Nov 14, 2006
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      NATAP http://natap.org/
      _______________________________________________

      Nonnucleoside Levels High in HIV-Infected Cirrhotics

      8th International Congress on Drug Therapy in HIV Infection
      November 12-16, 2006
      Glasgow, Scotland

      Mark Mascolini

      Plasma concentrations of nonnucleosides (NNRTIs)--especially nevirapine--proved high in hepatitis C virus (HCV)-coinfected patients with liver cirrhosis in a single-center Spanish study [1]. Cirrhosis did not affect protease inhibitor (PI) levels in this analysis. (Note from Jules Levin: I expressed an objection at the session saying I recall some studies have reported increased PI drug levels in patients with advanced fibrosis.)

      Pablo Barreiro and colleagues from Madrid's Carlos III Hospital ran this cross-sectional study on 279 HCV/HIV-infected patients taking standard doses of efavirenz, nevirapine, lopinavir/ritonavir, atazanavir/ritonavir, or unboosted atazanavir for at least 6 months. No one was taking drugs that may affect levels of these antiretrovirals, except for tenofovir. Everyone had adherence above 95%, as rated by pharmacy records. Barreiro determined liver fibrosis with the noninvasive FibroScan test; he excluded patients with a Child-Pugh class C liver disease prognosis.

      The study group had an average age of 45 years, 78% were men, and 85% were injecting drug users. One third were alcohol abusers, and body mass index averaged 22.6 kg/m2. The group's mean CD4 count stood at 511 and mean viral load at 2.01 log copies/mL (about 100 copies). Alanine aminotransferase averaged 54 IU/mL and HCV-RNA 5.3 log. Two thirds of the study group had HCV genotype 1, and one quarter had genotype 3.

      FibroScan determined that 103 people (37%) had cirrhosis, 80% of them with a Child-Pugh class A score and 20% with Child-Pugh B. Fibrosis did not correlate with PI levels, but Barreiro charted positive correlations between liver stiffness (measured as KPa) and levels of efavirenz (rho = 0.47) and nevirapine (rho = 0.22). The correlation with efavirenz was statistically significant (P = 0.001), whereas the correlation with nevirapine was not (P = 0.14). Child-Pugh class (A versus B) did not affect median concentrations of any antiretroviral studied.

      Efavirenz levels lay above 4 microg/mL in 5 of 16 people (31%) with cirrhosis versus 1 of 30 (3%) without cirrhosis. Among people taking nevirapine, 5 of 14 (36%) with cirrhosis had levels above 8 microg/mL, compared with 8 of 31 (26%) without cirrhosis.

      Barreiro concluded that HCV-coinfected people with compensated cirrhosis may have higher than normal concentrations of NNRTIs, especially efavirenz. He proposed that patients with cirrhosis may benefit from therapeutic drug monitoring to avoid NNRTI toxicity. Barriero also suggested his findings show that noninvasive tools like FibroScan can identify HCV/HIV-infected people who may need antiretroviral dose adjustments.

      Reference
      1. Barreiro P, Rodriguez-Novoa S, Labarga P, et al. Influence of the stage of liver fibrosis on plasma levels on antiretroviral drugs in HIV-infected patients with chronic hepatitis. 8th International Congress on Drug Therapy in HIV Infection, November 12-16, 2006, Glasgow. Abstract PL6.2.


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