Starting HIV treatment at a CD4 cell count above the currently recommended 350 cells/mm3 may help reduce the risk of liver damage for HIV-positive patients co-infected with hepatitis C virus, Spanish investigators report in a study published in the May edition of AIDS.
Liver disease caused by hepatitis C is an increasingly important cause of illness and death in HIV-positive patients. A recent study, for example, found that almost 12% of all deaths seen in HIV-positive patients in France was due to hepatitis C-related liver disease.
Although treatment for hepatitis C is available, it has a relatively low rate of success in HIV-positive patients. Given the limitations of currently available hepatitis C therapy it is therefore necessary to find alternative treatment options that delay the progress of liver disease in this group of patients.
Earlier research has shown that a suppressed immune system can increase the rate of liver fibrosis progression in co-infected patients. By contrast, other research has shown that immune recovery after the initiation of antiretroviral therapy can slow the rate of liver damage in such patients.
It is not known, however, if the initiation of HIV treatment earlier than the currently recommended threshold of 350 cells/mm3 could be beneficial.
There is inconsistency in treatment guidelines about the initiation of HIV treatment for co-infected patients. Both European and UK guidelines mention co-infected individuals as a group of patients who may wish to consider early initiation of HIV treatment, but this recommendation is not present in US guidelines.
Investigators at the La Paz Hospital in Madrid therefore conducted a retrospective study to evaluate the impact of HIV treatment on liver damage in HIV and hepatitis C co-infected patients with a high CD4 cell count.
All the patients had a CD4 cell count above 350 cells/mm3 and had undergone a liver biopsy. These were examined for evidence of fibrosis and fatty liver.
A total of 119 patients were included in the investigators’ analysis. Of these, 93 (78%) were receiving HIV treatment at the time of their biopsy. The median duration of antiretroviral therapy was 206 weeks.
Overall median CD4 cell count was 549 cells/mm3 and 40% had an undetectable HIV viral load. Median ALT [alanine aminotransferase] level at the time of biopsy was 87 iu/ml. A hepatitis C viral load above 800,000 copies iu/ml was present in almost 50% of patients, and 74% were infected with the hepatitis C genotypes 1 or 4, which are associated with a poorer response to anti-hepatitis C drugs.
The results of liver biopsies showed that 23% of patients had advanced fibrosis and that 66% had a fatty liver.
Statistical analysis showed that patients taking HIV treatment were significantly less likely to have evidence of liver damage than patients not taking such treatment (p = 0.017).
“In our study, we found that the use of highly active antiretroviral therapy appears to significantly decrease liver necroinflammatory activity in HIV-HCV-co-infected patients with CD4 T cell counts above 350 cells/mm3. The other two factors significantly associated in the multivariate analysis with increased necroinflammatory activity were ALT levels [p = 0.053] and a higher fibrosis score [p
They suggest that earlier HIV treatment may be beneficial for co-infected patients because it reduces HIV replication in the liver.
However, the researchers note that their study is limited by its single-centre, retrospective design. Nevertheless, they conclude that HIV treatment “might decrease hepatitis C activity in HIV-HCV-co-infected patients with CD4 cell counts of more than 350 cells/mm3. Consequently, our study supports the use of [HIV therapy] in HIV-HCV-co-infected patients to decrease liver damage regardless of CD4 cell counts.”
Pascual-Pareja JF et al. HAART is associated with lower hepatic necroinflammatory activity in HIV-hepatitis C virus-coinfected patients with CD4 cell count of more than 350 cells/mm3 at the time of liver biopsy. AIDS 23: 971-75, 2009.