Acute hepatitis C: Early therapy has a preventive effect

HIV-positive men who have sex with men (MSM) are particularly affected, but HIV-negative men are also becoming increasingly infected. Although the therapy is expensive, it is highly effective, preventative and overall cost-efficient when used early.

Higher treatment rates could reduce the number of new infections

Acute hepatitis C has spread worldwide since the early 1990s. HIV-positive men who have sex with men (MSM) are particularly affected, but HIV-negative men are also becoming increasingly infected. Although the therapy is expensive, it is highly effective, preventative and overall cost-efficient when used early, as Sanjay Bhagani, Royal Free Hospital, London, reported at CROI 2019 in Seattle, Washington, in March 2019.

In London’s Chelsea and Westminster, 27 cases of acute hepatitis C were described between 1997 and 2002, 26 were men and 25 were HIV positive. Risk factors were unprotected anal or vaginal intercourse in 21 men, intravenous drug use in 2 and syphilis in 9. "This was the beginning of sexually transmitted hepatitis C in HIV-positive men who have sex with men (MSM)," Bhagani explained. In the following years and months, hepatitis C cases from all over the world were described. The prevalence of hepatitis C virus (HCV) is significantly 1.6 times higher in HIV-infected persons than in HIV-negative persons. 7.5 times higher for MSM and 17.4 times higher for prisoners.

In the following years, knowledge about acute HCV infection in HIV-positive persons increased. Here is a summary of the insights gathered ever since:

Acute HCV infection rarely heals spontaneously, but usually turns into a chronic infection. If the HCV RNA decreases by less than 2 log stages after diagnosis, the transition to a chronic form is very likely. Diagnosis of MSM is generally made in the acute phase of infection. "This is the opportunity to intervene at an early stage," Bhagani stressed.

What do the guidelines recommend?

Based on this knowledge, the European AIDS Clinical Society developed an algorithm for the treatment of acute HCV in HCV/HIV-coinfected individuals. If a diagnosis of acute HCV infection is confirmed, the determination of HCV RNA is repeated after 4 weeks. If the HCV RNA has decreased by less than 2 log stages, treatment with direct-acting antivirals (DAA) should be started or patients should be included in a study. 

The EASL guidelines also recommend immediate treatment with DAA because it improves the outcome of patients. The immediate start of therapy is also cost-effective because it can prevent the transition to chronic infection. However, the ideal time for starting therapy is not yet known exactly.

Patients with acute HCV infection should be treated for 8 weeks with Sofosbuvir/Ledipasvir (genotype 1, 4, 5, 6) or Ombitasvir/Paritaprevir/Ritonavir (GT 1b). Due to similarities with the chronic infection, they may also receive Sofosbuvir/Velpatasvir (all GT), Glecaprevir/Pibrentasvir (all GT) or Elbasvir/Grazoprevir (GT 1b, 4) for 8 weeks.

The AASLD recommendations are more cautious. They foresee waiting up to 6 months to see if a spontaneous clearance occurs. Bhagani takes a critical view of this, however, because during this time further transmission of the virus by the patients is possible. A recently published cost-benefit analysis also showed that a delay in therapy beyond the first 6 months after diagnosis leads to a significant increase in costs. In addition, early DAA treatment for HIV-infected MSM is an excellent way to eradicate HCV infection by 2030.

However, the costs of therapy often stand in the way of early use. If the costs of therapy were within the range of the costs of penicillin, Bhagani believes that there would be no discussion about early therapy. However, "The cost of therapy is prohibitive."

Risk of reinfection

The risk of reinfection or late relapse after a sustained virological response is high for intravenous drug users and prisoners with a 5-year recurrence rate of 13.2% and 21.7% for HIV/HCV co-infection. 

Another problem is the high prevalence of HCV in HIV-negative MSM using a PrEP. In the Amsterdam PrEP study, 4.8% of the 375 participants were infected with HCV. Risk factors included younger age, more partners, injected drugs, chemsex, anal sex without a condom. Also in London, 8% of HIV-negative MSM screened showed acute HCV infection. "This epidemic has now spread from HIV-positive to HIV-negative MSM," the British expert noted. Unfortunately, these are men who are not regularly examined.

Therapy has a preventive effect

In the Netherlands, a programme began in 2015 in which all HIV/HCV-coinfected MSMs had free access to DAAs. 76% could be treated successfully. In the year following the start of the programme, 2016, the number of acute infections among HIV-positive MSM decreased by 51% compared to 2014. This proves a clear preventive effect of the therapy. A similar preventive effect of the therapy was seen in the Swiss HCVRee study, in a study in London and in the Spanish GeSIDA study.

In summary, Bhagani once again emphasized the benefits of immediate therapy. Higher treatment rates could reduce the number of new infections. However, the spread of HCV infection into the HIV-negative MSM community could counteract this. MSM using PrEP should also be screened. In addition, there is a high demand for an HCV vaccine.

Bhagani S, for Rockstroh J. Dynamics of acute HCV in Western Europe. CROI 2019, Seattle, Washington, March 6, 209, Abstract 112.