Disease progression

Effects of HIV on HCV disease progression

Studies of the natural history of HCV infection reveal that less than 50% of people with HCV infection (in the absence of HIV infection) clear HCV, with most people developing persistent HCV infection and chronic hepatitis. Spontaneous clearance is more common in younger people and women,14 whereas HIV co-infection is associated with a reduced HCV clearance rate.15 Chronic HCV infection may lead to hepatic fibrosis, which may ultimately progress to cirrhosis and liver failure or hepatocellular carcinoma (HCC). Progression is more rapid in people with significantly abnormal serum alanine aminotransferase (ALT) levels, in older people at the time of acquisition,16 and in people with co-morbidities such as heavy alcohol intake, obesity and co-infection with HIV and HBV. The progression to cirrhosis in people with HCV infection alone occurs in 10% of people after 20 years of infection.17 Cross-sectional studies have demonstrated higher rates of cirrhosis in people with HIV-HCV co-infection compared with people with HCV infection alone. After 10 years, the prevalence of cirrhosis in people with co-infection was 14.9% (versus 2.6% in HCV monoinfection) in one study and 25% (versus 6.5%) at 15 years in another study.18,19 HIV accelerates the progression of liver disease in people with haemophilia with HIV infection as well as in other populations.20 A small case control study suggested that HCC occurs at a younger age and sooner in the course of HCV infection in people with co-infection.21 Progression of HIV-related immunodeficiency is associated with HCV disease progression, with lower CD4 T-lymphocyte (CD4) cell counts being associated with hepatic fibrosis and liver failure.22,23 Significant levels of alcohol consumption are associated with greater disease progression in people with HIV-HCV co-infection. People with HIV-HCV co-infection and mild fibrosis on liver biopsy may experience significant progression of hepatic fibrosis over a 3-year period.24

Effects of HCV infection on HIV disease progression

Studies of the influence of HCV infection on the progression of HIV disease have been contradictory, with some studies suggesting an increase in HIV disease progression in people with HIV-HCV co-infection and others demonstrating no influence on disease progression.25

Effects of cART on HCV disease

Although cART has no direct antiviral activity on HCV replication, cART results in an initial increase and subsequent decline in HCV RNA,26,27 yet HCV clearance with cART has rarely been reported.28 The changes in HCV RNA following cART are largely thought to be secondary to improvement in HCV-specific immunity resulting in better control of HCV replication. People with HIV-HCV co-infection have higher HCV RNA than those with HCV monoinfection.29 It is unlikely that cART alone is sufficiently effective as a primary treatment strategy for HCV infection in people with co-infection. However, where treatment of HCV is contraindicated or unavailable, effective cART may be important in slowing liver disease progression.30 In decompensated cirrhosis, cART is associated with a reduction in the mortality rate when initiated after the first episode of decompensation.31

Antiretroviral hepatotoxicity

Hepatotoxicity in the setting of HIV-HCV co-infection may be directly related to multiple antiretroviral agents. Agents known to have unfavourable hepatic profiles such as nevirapine, didanosine and stavudine should be avoided for this reason.  Zidovudine is avoided because it causes haemolysis in combination with ribavirin.32 Newer agents such as rilpivirine, etravirine and raltegravir appear safe in the setting of HIV-HCV co-infection, although the incidence of hepatic adverse effects may be higher in co-infection than in HIV monoinfection.33,34  The incidence of hepatic adverse events related to dolutegravir in HIV-HCV co-infection has not yet been reported.

Immune restoration disease

Similar to HIV-HBV co-infection, hepatotoxicity can rarely occur secondary to immune restoration disease.35 In HIV-HCV co-infection, this is even less common, but may manifest as an elevation of serum hepatic transaminases levels in the first few months after the introduction of cART. It is unclear what threshold should be used regarding withdrawal of cART in this setting or whether HCV therapy should be instituted. One small study suggested that subjects with symptomatic drug-induced liver injury could successfully recommence cART if pegylated interferon and ribavirin were used, although rates of HCV clearance with this strategy were low.36 Others have suggested that treating HCV before HIV may reduce the risk of cART-associated hepatoxicity.37