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.
(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.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
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.
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.
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%
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
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
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.