Liver-related Death Among HIV/hepatitis C Virus-co-infected Individuals

Implications for the Era of Directly Acting Antivirals

Daniel Grint; Lars Peters; Juergen K. Rockstroh; Aza Rakmanova; Tatiana Trofimova; Karine Lacombe; Igor Karpov; Massimo Galli; Pere Domingo; Ole Kirk; Jens D. Lundgren; Amanda Mocroft


AIDS. 2015;29(10):1205-1215. 

In This Article

Abstract and Introduction


Background: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.

Methods: Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.

Results: LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35–45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1–9.6; and sHR 2.5, 95% CI 1.5–4.2 vs. F0/F1, respectively), CD4+ cell count (sHR 0.83, 95% CI 0.73–0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3–3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7–2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6–13.5; and sHR 14.0%, 95% CI 10.3–18.3, respectively).

Conclusion: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4+ cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.


The substantial declines in HIV-related mortality, as a consequence of the introduction of combination antiretroviral therapy (cART), have seen liver-related death (LRD) assume increasing relative importance among HIV-positive individuals.[1,2] Although progression of liver disease is common with hepatitis C virus (HCV) infection and known to be accelerated in the presence of HIV,[3] LRD is often associated with older age as complications of HCV-related liver disease usually take decades to develop.[4] During this period, HCV-co-infected individuals have many competing risks of death, such as mortality associated with injecting drug use, AIDS, cardiovascular disease, malignancies, bacterial infections, violent death and renal disease.[2]

While the uptake of treatment for HCV has so far been low among HIV/HCV-co-infected individuals in Europe, in particular, among injecting drug users (IDUs), this is partially explained by the costs of treatment, potential contraindication to interferon-based treatments, anticipated poor treatment adherence and low treatment efficacy of pegylated interferon and ribavirin.[5] However, with the recent approval of less toxic, oral, directly acting antivirals (DAAs) for HCV, fewer co-infected individuals will have contraindications to HCV treatment, while treatment outcomes will be significantly improved and approach the HCV cure rate of above 90% seen for HCV-monoinfected individuals.[6,7]

The potential benefits of curative treatment with new DAAs are numerous, including reductions in fibrosis progression, LRD and extra-hepatic manifestations, along with limiting ongoing transmission.[8] However, regardless of the advances in HCV treatment, the approximate costs of [Euro sign]50 000–90 000 per treatment for the currently approved DAAs and the expectation that new oral combination regimens will be more expensive still[9] will, in many countries, necessitate the prioritization of individuals for treatment. Therefore, a better understanding of the spectrum of causes of death among HIV/HCV-co-infected individuals, factors that affect progression to LRD and potential competing risks is essential in determining who to prioritize for treatment of HCV infection.

The aims of this study were to describe causes of death among HIV/HCV-co-infected individuals naive to interferon-based treatment, to identify factors associated with LRD and to provide guidance on who should be prioritized for treatment of HCV infection with DAAs.