Hepatitis C co-infection blunts response to antiretroviral therapy

Christopher Gadd
Published: 25 August 2005

Co-infection with the hepatitis C virus (HCV) reduces CD4 cell count gains by an average of 33 cells/mm3 after a year of antiretroviral therapy in HIV-positive patients, according to the results of a meta-analysis published in the 1st September edition of Clinical Infectious Diseases.

This finding may support calls for the earlier initiation of antiretroviral or anti-HCV therapy in co-infected patients, in order to optimise immune restoration or to eradicate HCV from the body prior to starting HIV treatment.

Previous studies examining the influence of HCV infection on the response to anti-HIV treatment have produced mixed findings. Some investigators have found that co-infection blunts the rises in CD4 cell count, while others have seen no difference between HIV patients with and without HCV.

To understand the relationship between HCV and immune restoration more fully, investigators from the United States carried out a ‘meta-analysis’ of clinical trials. This is a method of combining the results from a set of similar studies to work out the average overall finding. Meta-analyses are regarded as providing more reliable results than individual studies as they contain more participants and data collected in different geographical areas and at different times.

After an extensive search of the medical literature, the researchers identified eight studies that were eligible for inclusion in their meta-analysis, including a total of 6216 patients. These studies all compared CD4 cell count rises after the initiation of antiretroviral therapy in HIV-positive patients with and without HCV co-infection. The studies took place in North America, Europe and Australia.

After weighting each study according to the degree of variability in its results, the researchers calculated that the HCV co-infected patients had a CD4 cell count rise that was a mean of 33.4 cells/mm3 (95% confidence interval: 23.5 – 43.4 cells/mm3) lower than the patients with HIV alone. They calculated this from the first reported CD4 cell count change measured after twelve months in each study.

“Our meta-analysis showed that the increase in the CD4 cell count in patients who started receiving highly active antiretroviral therapy (HAART) for HIV infection is significantly lower if they have HCV co-infection,” they conclude. “HIV-infected patients are likely to have a better immunological response to antiretroviral therapy if they are not co-infected with HCV.”

However, the researchers note that their study does not indicate that the co-infected patients have a poorer outcome. “Future research should examine whether an impaired immunologic response corresponds with meaningful virologic and clinical outcomes,” they write.

Studies including patients co-infected with hepatitis B were not excluded from their analysis, as this virus is not believed to affect the response to anti-HIV treatment.

The investigators speculate that the higher number of intravenous drug users in the HCV co-infected group may explain their findings, at least in part. “This population often has less access to health care and typically has worse adherence to HIV regimens, compared with the population of patients who contracted HIV infection by other means,” they explain.

“Adherence to HAART in this population may be directly related to improvements in the CD4 cell count,” they write.

The researchers point out that their analysis may have been affected by a number of factors that were not reported in the original research papers. These include baseline CD4 cell counts, HIV viral loads and the possibility that some of the patients with HCV antibodies may have cleared the virus before starting anti-HIV therapy.

However, they found that the year in which antiretroviral therapy was started, whether the studies followed patients prospectively or used previously-collected data and the length of follow-up had no significant effect on the outcome. Similarly, no one study had a disproportionate effect on the outcome of the meta-analysis.

Reference

Farmer Miller M et al. Impact of hepatitis C virus on immune restoration in HIV-infected patients who start highly active antiretroviral therapy: a meta-analysis. Clin Infect Dis 41: 713-720, 2005.

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