Coinfection

ICAAC 2011: Maraviroc May Reduce Liver Fibrosis in HIV/HCV Coinfected People

Adding the CCR5 blocker maraviroc (Selzentry) to an antiretroviral regimen reduced liver stiffness, an indicator of fibrosis, according to a study presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011) this week in Chicago.

Liver disease tends to progress more rapidly among HIV/HCV coinfected people compared to those with hepatitis C virus (HCV) alone. Research suggests that liver injury in HIV positive people is associated with persistent inflammation, and maraviroc has been shown to dampen inflammation in some studies.

Paola Nasta from the University of Brescia in Italy and colleagues evaluated the influence of CCR5 inhibition with maraviroc on changes in liver stiffness among HIV/HCV coinfected patients.

The chemokine receptor CCR5 is expressed on stellate cells in the liver, which produce fibrous scar material, and is strongly up-regulated in experimental models of fibrogenesis, the researchers noted as background. CCR5 inhibition has been shown to reduce liver fibrosis in experimental mouse models.

The non-invasive FibroScan test measures liver stiffness using sound waves. Greater liver stiffness (expressed in kilopascals, or kPa) is correlated with higher fibrosis scores, but the method is not as accurate as liver biopsy for distinguishing intermediate stages.

The study included 62 HIV/HCV coinfected patients who had not yet undergone hepatitis C treatment but had undetectable HIV viral load on stable combination antiretroviral therapy (ART) consisting of ritonavir-boosted atazanavir (Reyataz) plus tenofovir/emtricitabine (the drugs in Truvada).

Most participants (about 80%) were men, the average age was 46 years, the median CD4 T-cell count was approximately 500 cells/mm3. More than 90% had difficult-to-treat HCV genotypes 1 or 4. Average liver stiffness at baseline was about 7 kPa, indicating minimal fibrosis; biochemical liver markers were similar in both groups, indicating a comparable extent of liver disease progression.

Participants were randomly assigned (1:1) to either continue on the baseline ART regimen (control arm) or to add 150 mg twice-daily maraviroc for 96 weeks.

The researchers assessed clinical, virological, immunological, metabolic, and liver function parameters and measured liver stiffness at baseline and every 24 weeks. A total of 44 people (23 in the maraviroc arm, 21 in the control arm) completed 24 weeks of randomized treatment and were included in this preliminary analysis.

Results

Based on these findings, the investigators concluded, "To add maraviroc to the current [ART regimen] may reduce liver stiffness in HIV/HCV coinfected subjects."

Investigator affiliations: University of Brescia, Brescia, Italy.

9/23/11

Reference

P Nasta, F Gatti, F Borghi, et al. 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. Abstract H3-810.