People with HIV and hepatitis C virus (HCV) co-infection who have advanced liver fibrosis should be prioritised for therapy with new anti-HCV drugs, investigators argue in AIDS. Analysis of people in the EuroSIDA cohort showed that people with co-infection who have moderate (F2/F3) or advanced (F4) liver fibrosis had a significant risk of liver-related death. Early antiretroviral treatment (ART) was advocated for all patients as a way of avoiding liver disease and delaying the need for HCV therapy.
A significant number of people with HIV have HCV co-infection. The progression of HCV-related liver fibrosis is accelerated in people with untreated HIV infection, and liver disease caused by HCV is now a leading cause of death in these individuals. The development of direct-acting antiviral agents (DAAs) has revolutionised care for people with HCV. These new drugs are potent, tolerable, have manageable interactions and are associated with high cure rates. But a major drawback is their cost, a single course of treatment costing between 50,000 and 90,000 euros. It is highly likely, therefore, that access to DAAs for people with HIV and HCV co-infection will be rationed, with priority given to people with the greatest need – a high risk of liver-related death (LRD) in the short-to-medium term.
Investigators from the EuroSIDA cohort therefore designed a study to determine the characteristics associated with an increased risk of liver-related death for people with co-infection in the EuroSIDA cohort.
Their study sample comprised 3941 individuals with HIV and HCV co-infection who received care after 2000. None received HCV treatment based on interferon therapies.
Most of the patients were white (94%) and male (68%). The median age was 37 years and 70% were people who inject drugs.
Patients were followed for a median of 3.5 years and contributed just over 16,000 person-years of follow-up (PYFU). During this time, 670 deaths were recorded. The overall morality incidence was therefore 42 per 1000 PYFU. Just over a fifth (22%) of deaths were categorised as liver-related; the liver-related death incidence was 9.0 per 1000 PYFU.
The authors emphasise that liver-related death was the second most common cause of death after AIDS (24%).
Overall, mortality peaked among people aged 55 and over. However, rates of liver-related death were highest among people in the 35-45 and 45-55 age groups.
Mortality rates were significantly elevated among those with detectable HCV RNA, alcohol abuse and individuals with hepatitis B virus surface antigen (HBsAg) positivity.
Compared to people with no or mild fibrosis (F0/F1), death rates were 35 times higher among people with F4 stage fibrosis compared to those with stages F0/F1 (crude death rates [CDR] = 42.2 vs 1.2), and were eight times higher for individuals with F2/3 fibrosis (CDR = 10.0).
After controlling for potential confounders, fibrosis stage was the single biggest risk factor for liver-related death. Compared to people with F0/F1 fibrosis, those with F4 fibrosis had a sixfold increase in the risk of liver-related death (p < 0.0001), with the risk increased 2.5-fold for people with F2/F3 fibrosis (p < 0.0001).
Other risk factors were HBsAg positivity (p = 0.0024), infection with HCV for ten years or more (p = 0.041), lower CD4 cell count and age between 35 and 45 years (compared to younger age, p = 0.045).
When the investigators omitted baseline CD4 count from their model, a low nadir (lowest ever) CD4 count also became predictive of liver-related death (p = 0.0045).
The five-year probability of liver-related death was clearly related to fibrosis stage. It was low for people with F0/F1 disease (2%), but substantial for individuals with stages F2/F3 (10%) and F4 (14%).
CD4 count was related to the risk of liver-related death at all fibrosis levels. The five-year probability of liver-related death was lowest for individuals with F0/F1 fibrosis and a CD4 count above 300 cells/mm3 (1.7%), increasing to 3.3% for patients with F0/F1 disease and a lower CD4 count. People with F2 stage disease and above had a 9% five-year mortality probability if their CD4 count was above 300 cells/mm3, increasing to 15% if their CD4 count was below this level.
“Those with significant liver fibrosis (F2 >) should be prioritized for treatment with DAAs,” conclude the authors. “It is essential to identify co-infected individuals as soon as possible so that they may start cART [combination antiretroviral treatment] early in the course of HIV infection…to prevent rapid progression of liver fibrosis and reduce the need for expensive treatments.”
Grint D et al. Liver-related death among HIV/hepatitis C-virus-co-infected individuals: implications for the era of directly acting antivirals. AIDS 29: 1205-15, 2015.