 |
|
|
| |
Adding Maraviroc May Reduce Liver Stiffness in People With HCV and HIV
|
| |
| |
51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago
from jules: I talked with author at poster today who said she would use MVC in patients witcoinfection but not in patients with advanced disease because she had some concerns that MVC might have some mixed effects, although HCV viral load did not go up significantly she mentioned the increase as a concern to me.
Mark Mascolini
Adding maraviroc to an atazanavir-based regimen in HIV/HCV-coinfected people not yet taking anti-HCV therapy decreased liver fibrosis determined by transient elastometry, according to preliminary results of an ongoing randomized trial at the University of Brescia in Italy.
Liver fibrosis progresses faster in HCV-positive people coinfected with HIV than in those without HIV. In human liver cell studies, the CCR5 receptor is strongly upregulated on stellate cells [2], promotes migration of these cells to injury sites, leads to recruitment of other cell types including Kupffer cells, and thus facilitates hepatic stellate cell activation. CCR5-deficient mice have reduced hepatic fibrogenesis [3]. Stellate cells are the main cell type involved liver fibrosis. For these reasons, the University of Brescia team planned this randomized trial of antiretroviral intensification with maraviroc in HIV/HCV-coinfected people not being treated for their HCV infection.
All study participants had an undetectable HIV load while taking a stable regimen of atazanavir/ritonavir plus tenofovir/emtricitabine, and all had a Child-Pugh score below A6. The investigators randomized them to maintain their current regimen or to add 150 mg of maraviroc twice daily for 96 weeks. They measured liver stiffness by transient elastometry at baseline and every 24 weeks, using standard staging categories: stage I: <7.1 kPa; stage II: 7.1 to 9.4 kPa; stage III: 9.5 to 12.4 kPa; stage IV: >/= 12.5 kPa.
Of the 59 patients enrolled through April 2011, 78% were men. No baseline measures differed significantly between the maraviroc group and the control group. Median age stood at 46 (interquartile range [IQR] 43 to 48), median CD4 count at 506 (IQR 405 to 685), median aspartate aminotransferase at 42 IU/mL (IQR 31 to 59), median alanine aminotransferase at 66 IU/mL (IQR 45 to 96), and HCV load at 5.8 log10 IU/mL (IQR 5.4 to 6.2).
Median liver stiffness measured 7.4 kPa (IQR 5.4 to 10) in the maraviroc arm and 6.8 kPa (IQR 5.3 to 9.5) in the maintenance arm, a nonsignificant difference. APRI score and FIB4 did not differ significantly between the two study groups. Fifty-five study participants (93%) had HIV genotype 1 or 4.
Forty-four people, 23 in the maraviroc arm and 21 in the control arm, completed 24 weeks of follow-up at the time of this report. Median liver stiffness decreased among people who added maraviroc (-0.8 kPa, IQR -1.8 to +0.3) while increasing in the maintenance group (+0.1 kPa, IQR -0.7 to +0.9) (P = 0.03). Eight people, 4 in each study arm, had liver stiffness at or above 12.5 kPa when the trial began. In this subset median liver stiffness fell in the maraviroc group (-2.2 kPa) while rising in the control group (+4.5 kPa) (P = 0.04).
Through 24 weeks liver stiffness stage changed in 6 people in the maraviroc arm, improving in 5 and worsening in 1. In the maintenance group, liver stiffness stage changed in 7 people, improving in 2 and worsening in 5. Compared with the control group, the maraviroc group had an 80% lower chance of worsening liver stiffness stage (odds ratio 0.2), though this association fell short of statistical significance (P = 0.07).
HCV RNA load did not change significantly during the study in either group.
The Brescia investigators stressed that their findings are preliminary. "The consequence of CCR5 inhibition on intrahepatic immunosurveillance is unknown," they cautioned, and for now "liver function and HCV RNA should be controlled when maraviroc is included" in an antiretroviral regimen.
References
1. Nasta P, Gatti F, Borghi F, Chiari E, Paderni A, Carosi G. Liver stiffness (LS) change in HIV-Hepatitis C (HCV) coinfected patients treated with CCR5 inhibitor based antiretroviral therapy. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H3-810.
2. Schwabe RF, Bataller R, Brenner DA. Human hepatic stellate cells express CCR5 and RANTES to induce proliferation and migration. Am J Physiol Gastrointest Liver Physiol. 2003;285:G949-958. http://ajpgi.physiology.org/content/285/5/G949.long.
3. Seki E, De Minicis S, Gwak GY, et al. CCR1 and CCR5 promote hepatic fibrosis in mice. J Clin Invest. 2009;119:1858-1870. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701864/?tool=pubmed.
|
| |
|
|
|
|
|
