Early HAART may slow liver disease in HIV/HCV co-infection

Results from a case-controlled study on the effect of HAART on liver fibrosis in patients co-infected with both HIV and hepatitis C virus (HCV) have concluded that, under certain circumstances, the early use of HAART may slow down liver disease progression. The results of this French study were published in the November 5^th issue of the journal, AIDS.

There remains some disagreement about whether HIV or HCV should be treated first in co-infected individuals. Some experts recommend that co-infected patients begin HIV therapy first, since once HIV is under control and CD4 cell counts rise, people respond better to pegylated interferon/ribavirin therapy, and are better able to tolerate the side-effects of HCV therapy.

On the other hand, in people with mild HIV disease but progressive liver disease, it may be beneficial to treat HCV first. Furthermore, initial HCV therapy may improve patients’ ability to later tolerate HIV medications.

The aims of this study were to assess the impact of HIV infection on the rate of liver fibrosis progression and to identifty the role of HAART in the progression of HCV-related liver disease. Between January 1997 and June 2000, 116 HIV/HCV co-infected patients were matched by gender, age at infection and duration of infection, with 235 patients infected with HCV alone. In order to assess the impact of HAART on liver fibrosis, the 91 (78%) of co-infected patients receiving HAART at the time of liver biopsy were stratified by fibrosis severity using the METAVIR score: F0-F2 (none-moderate) vs. F3-F4 (severe). There were no clinical or biological differences between the two groups of co-infected patients, although more co-infected patients had a history of injecting drug use and/or consumed more than 50g of alcohol a day.

When comparing the co-infected with the mono-infected patients, the investigators found that among co-infected patients an F3-F4 METAVIR score was significantly more frequent (26% vs. 7%; p

The investigators then compared the two groups of co-infected patients, as defined by METAVIR scores. During univariate analysis, although they found that the delay between presumed HCV infection and HAART initiation was significantly longer in those with more severe fibrosis, when they adjusted for duration of disease, age at HCV infection and CD4 cell count, this was no longer statistically significant.

The investigators then performed a second analysis excluding 19 patients with a METAVIR score for F4 (cirrhosis) due, they explain, “to uncertainty regarding the date of onset of liver cirrhosis.” This time they found significant differences that remained so in multivariate analysis. The patients with moderate fibrosis had a significantly shorter delay from presumed date of HCV infection to commencing HAART (adjOR 1.16; p=0.03) and longer duration of HAART (adjOR 0.96; p=0.06) compared with those with severe fibrosis.

A third analysis in the patients without cirrhosis focusing on the mean rate of fibrosis progression found that, in a multiple regression model adjusting for duration of disease, age at HCV infection and CD4 cell count, mean rate of fibrosis progression was significantly slower among patients who had been on HAART longer (ß= -0.190; p=0.02) and who had a shorter delay between the time of presumed HCV infection and HAART initiation (ß=0.069; p=0.02).

Currently, it is unknown why HAART might beneficially impact liver fibrosis, and the investigators do concede that “some antiretroviral treatments may cause liver toxicity” and that the “best way to interrupt hepatic fibrosis is to initiate a pegylated-interferon/ribavirin treatment combination.” They conclude, however, that “when HCV treatment cannot be implement due to treatment contra-indications or adverse events, patients may benefit from early antiretroviral treatment.”

For more on the treatment of HIV/HCV co-infection, read October’s AIDS Treatment Update and the hepatitis C overview on aidsmap.