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

This article is more than 20 years old. Click here for more recent articles on this topic

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 5th 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.

Glossary

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

regression

Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

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.

References

Mariné-Barjoan E et al. Impact of antiretroviral treatment on progression of hepatic fibrosis in HIV/hepatitis C virus co-infected patients. AIDS 18 (16); 2163-2170, 2004.