CROI: Long-term use of HIV therapy has no strong association with liver-related death

There is no strong association between the longer term use of potent anti-HIV therapy and the death from liver disease, according to a study presented to the Thirteenth Conference on Opportunistic Infections and Retroviruses in Denver in early February.

However, when the investigators controlled for the beneficial effects which antiretroviral therapy has on CD4 cell count, they found that there was some evidence that antiretroviral therapy use in the longer term was associated with an increased risk of liver disease. Importantly, the international team of researchers also found that low CD4 cell count, coinfection with hepatitis B or hepatitis C and age are the main risk factors for death from liver-related disease amongst HIV-positive individuals who took antiretroviral therapy for up to seven years.

There has been concern that extended use of anti-HIV therapy may be associated with a risk of impaired liver function or liver-related death, particularly for individuals who are coinfected with either hepatitis B or hepatitis C virus.

Accordingly, investigators from the D:A:D study (Data collection on Adverse events of anti-HIV Drugs) prospectively gathered data on over 23,000 individuals, and calculated the rate of liver-related death according to the number of years of exposure to powerful antiretroviral therapy. The investigators also looked at the risk factors for liver-related death.

Just under 77,000 person-years of follow-up were available for the investigators analysis. A total of 1248 individuals died, with 183 deaths (15%) attributed to liver-related causes.

Of the people who died because of liver disease, 17% had active hepatitis B virus, 66% had hepatitis C virus and 7% were coinfected with both. The median duration of use of potent antiretroviral therapy amongst people dying of liver disease was three years.

The investigators then looked at the independent risk factors for death from liver disease. These were a low baseline CD4 cell count (risk ratio [RR], 1.18); older age (RR, 1.34), injecting drug use (RR, 2.49), coinfection with hepatitis B virus (RR, 2.31), and coinfection with hepatitis C virus (RR, 7.30).

When the investigators looked at the rate of liver-related death according to the length of exposure to potent antiretroviral therapy, they failed to find any significant association. However, when they adjusted these results for CD4 cell count at the time of death - therefore taking into account the beneficial effects of powerful HIV therapy on immune function - a significant association emerged (p = 0.03). They cautioned, however that further data were required before firm conclusions could be drawn and concluded that the main risk factors for liver-related death were “low CD4 cell counts, chronic coinfection with hepatitis B/hepatitis C and age.”