Study supports early initiation of HIV treatment by HIV/hepatitis C co-infected patients

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Early initiation of HIV treatment can help prevent liver damage in HIV/hepatitis C co-infected patients, French investigators report in the February edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators suggest that, in co-infected patients who have not responded to treatment for hepatitis C, “early highly active antiretroviral therapy may help to protect the liver”.

The study adds to a growing body of research suggesting that HIV treatment can help reduce the risk of liver-related illness and death in co-infected patients. Current UK HIV treatment guidelines state that co-infected patients should be encouraged to start treatment when their CD4 cell count is in the region of 350 cells/mm3. A separate Danish study reported here on aidsmap.com showed that the preservation of a functioning immune system reduced the risk of liver-related death for co-infected patients to such an extent that it was no different to that seen in patients only infected with hepatitis C.

Liver disease is now a leading cause of death in HIV-positive patients co-infected with hepatitis C. Before HIV treatment became available, hepatitis C co-infection was associated with the rapid progression of liver fibrosis (hardening of the liver) and cirrhosis (scarring of the liver).

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.

biopsy

A procedure to remove a small sample of tissue so that it can be examined for signs of disease.

non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non-serious condition called fatty liver, by which fat accumulates in the liver cells. A small group of people with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH).

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

multivariate analysis

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

There is debate about the impact of HIV treatment on the progression of liver disease in patients co-infected with hepatitis C, and therefore French investigators designed a retrospective study involving 395 co-infected patients to examine the progression of liver disease in co-infected patients in the era of effective HIV treatment.

All the patients had had a liver biopsy that showed at least mild liver fibrosis and had a CD4 cell count above 200 cells/mm3. None of the patients had taken antiretroviral treatment in the three months before entry to the study.

The patients were divided into two groups according to the extent of fibrosis they had developed. The first group included 286 patients who had less severe fibrosis (stages 1 and 2); the second, 109 individuals with more advanced fibrosis (stages 3 and 4).

Liver biopsies were performed on the patients an average of seven months before entry to the study. HIV treatment was started by 297 patients (75%) before or at the time of liver biopsy.

In the first set of statistical analysis, the factors associated with more advanced fibrosis were:

  • Older age.
  • Treatment with anti-HIV drugs.
  • Longer interval between HIV diagnosis and starting HIV treatment.
  • Longer duration of HIV treatment.
  • Taking a nucleoside reverse transcriptase inhibitor-based (NRTI) HIV-treatment combination.
  • Treatment with 3TC (lamivudine, Epivir).
  • Steatosis (fatty liver).

However, in multivariate analysis that controlled for possible confounding factors, the researchers found that only two factors were associated with severe fibrosis: the interval between HIV diagnosis and starting HIV treatment (for each year, odds ratio 1.084, 95% confidence interval [CI], 1.029-1.143, p = 0.025) and having a fatty liver (odds ratio, 1.912, 95% CI, 1.179-3.102, p = 0.0086).

“The interval between diagnosis of HIV infection and initiation of antiretroviral therapy was significantly longer with significant fibrosis”, comment the investigators.

They note, however, that these patients with more advanced fibrosis were more likely to be HIV treatment-experienced and to have received anti-HIV drugs for longer than individuals with less advanced fibrosis.

“This suggests that it is not the prescription or duration of highly active antiretroviral therapy that protects from hepatitic fibrosis but, rather, its early initiation after diagnosis of HIV infection,” add the investigators.

References

Bani-Sadr F et al. Does early antiretroviral treatment prevent liver fibrosis in HIV/HCV coinfected patients? J Acquir Immune Defic Syndr: 50 234-36, 2009.