An 8-week course of grazoprevir/elbasvir (Zepatier) produced sustained virological response in most HIV-positive gay men with recent hepatitis C virus (HCV) genotype 1 or 4 infection, according to a presentation at the 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018) last month in Boston.
Researchers recommended that prompt, brief treatment during acute infection could halt onward transmission and contribute to the elimination of HCV among HIV-positive men who have sex with men, given that spontaneous clearance is uncommon in this population.
Direct-acting antivirals (DAAs) have made treatment for chronic hepatitis C shorter, better tolerated and much more effective, even for people – such as those with HIV/HCV co-infection – who were considered difficult to treat with interferon-based therapy. This has led experts to ask if treatment may also be shortened for people with acute hepatitis C, meaning the first six months after infection.
Studies have shown that 8 weeks of sofosbuvir/ledipasvir (Harvoni) is adequate for treatment of genotype 1 acute HCV infection in HIV-negative people, and one study found that even a 6-week course works well for this group. But stopping at 6 weeks led to an unexpectedly high relapse rate for people with HIV/HCV co-infection.
Anne Boerekamps of Erasmus University Medical Centre in Rotterdam, the Netherlands, and colleagues evaluated the efficacy of 8-week treatment of acute HCV using Merck's dual DAA regimen consisting of the HCV NS3/4 protease inhibitor grazoprevir and the NS5A inhibitor elbasvir. This regimen is not pangenotypic and is recommended only for HCV genotypes 1 and 4.
The Dutch Acute HCV in HIV study (DAHHS2) included 80 participants. Fifteen hospitals in the Netherlands and Belgium referred patients diagnosed with acute HCV to nine DAHHS study centres.
All participants were men who have sex with men, with an average age of 47 years. She noted that thanks to the Netherlands' good needle exchange and harm reduction programs, HCV infection rates are low among people who inject drugs and most participants were assumed to have acquired HCV through sexual transmission.
More than 90% of participants were HIV positive. All of these were on antiretroviral therapy (ART), most had undetectable HIV viral load and the median baseline CD4 count was approximately 600 cells/mm3. Nearly two-thirds (64%) had HCV genotype 1a, none had 1b and 36% had genotype 4. In about a quarter of cases, this was a second or subsequent infection.
Everyone in this single-arm study received 100/50mg grazoprevir/elbasvir once daily for 8 weeks; there was no placebo or comparator regimen arm. Treatment was started no later than 26 weeks after the estimated date of infection. The primary endpoint was sustained virological response (SVR), or continued undetectable HCV RNA at 12 weeks post-treatment (SVR12).
Boerekamps reported interim findings from 63 participants who completed therapy and 12 weeks of post-treatment follow-up. All but four achieved SVR12. Phylogenetic testing showed that only one case was a relapse while the other three were reinfections. Thus, the SVR12 rate was 98% (or 94% if relapses were counted as treatment failures).
Treatment was generally safe and well tolerated. Only three people experienced serious adverse events, and these were not treatment-related. The most common adverse events were gastrointestinal complaints (24%), sexually transmitted infections (24%) and "common cold" symptoms (22%).
Based on these findings, the researchers concluded, an 8-week course of grazoprevir/elbasvir "is highly effective for the treatment of acute HCV."
Boerekamps noted that DAA regimens are currently only approved for chronic, not acute, HCV infection, which limits reimbursement. She added that although this regimen was highly effective, a pangenotypic regimen would be ideal.
Boerekamps and co-investigator Bart Rijnders – who reported at last year's CROI that acute HCV infections among gay men in the Netherlands had declined dramatically after the country instituted universal access to DAAs – told reporters that treatment with a short regimen during acute infection would be cost saving for a population that is at high risk of transmitting HCV to others.