Treatment for 12 weeks with a
co-formulation of sofosbuvir and ledipasvir led to sustained response for all
participants with HIV and HCV co-infection who had genotype 1 hepatitis C virus (HCV) followed for 12 weeks
post-treatment, according to interim findings from the ERADICATE study
presented on Thursday at the 49th Annual Meeting of the European Association for the Study of the Liver in London.
Anu Osinusi from the US National Institute of
Allergy and Infectious Diseases (NIAID) and colleagues tested a once-daily fixed-dose
combination pill containing the recently approved HCV polymerase inhibitor
sofosbuvir (Sovaldi) plus the NS5A
inhibitor ledipasvir (400/90mg) in people with HIV and hepatitis C co-infection.
Historically, people with HIV and HCV co-infection have not
responded as well to interferon-based therapy as HIV-negative people with HCV alone,
but recent data suggest that
interferon-free direct-acting antiviral regimens may be equally effective in
people with HIV. The PHOTON-1 study testing sofosbuvir
plus ribavirin found that people with co-infection had sustained virological response
rates at 12 weeks post-treatment (SVR12) similar to those previously seen in
HCV mono-infected patients.
The NIAID ERADICATE trial was an investigator-initiated
study that included 50 HIV-positive people with genotype 1 HCV co-infection;
about 80% had harder-to-treat subtype 1a. A majority were men, most were
African-American and the median age was approximately 58 years. About
one-quarter had advanced liver fibrosis (stage F3), but none had cirrhosis.
divided into two groups according to HIV treatment status. The ARV-untreated
group included 13 people who were not on antiretroviral therapy (ART) and had
either a stable CD4 cell count and HIV RNA below 500 copies/ml or a CD4 cell count
greater than 500 cells/mm3 (above the threshold for starting ART in previous
HIV treatment guidelines). The median CD4 count was 687 cells/mm3.
The ARV-treated group
included 37 people who had been on their current ART regimen for at least eight weeks,
had undetectable HIV RNA (<40 copies/ml) and had a CD4 count greater than 100
cells/mm3 (median 576 cells/mm3). Treated participants
used antiretrovirals that do not have clinically meaningful interactions with
sofosbuvir or ledipasvir. Everyone was on tenofovir/FTC (the drugs in
Truvada); in addition, 41% used
efavirenz (Sustiva), 27% used
raltegravir (Isentress) and 21% used
All participants were
treated with the sofosbuvir/ledipasvir co-formulation for 12 weeks. The
ARV-untreated group, which started sooner, had long enough follow-up to
determine SVR12, which is considered a cure for hepatitis C. The ARV-treated group was still
being followed, but a majority had SVR4 data available. SVR4 cannot yet be
considered a cure as some people still relapse after this point.
reached undetectable HCV RNA by week 4 of treatment and had continued
virological response at the end of treatment.
In the ARV-untreated
group, all 10 participants (100%) followed through 12 weeks post-treatment
achieved SVR12 in an observed analysis. In the ARV-treated group, 100% of the
22 patients followed through post-treatment to week 4 achieved SVR4. Among 10 ARV-treated
participants who reached post-treatment week 12, the SVR12 rate remained at
Looking at HIV
outcomes, in the ARV-untreated group there were no clinically significant
changes in HIV RNA during hepatitis C treatment. One person in the ARV-treated
group experienced a transient HIV RNA increase after missing antiretrovirals
for four days, but resumed HIV suppression on the same regimen. CD4 cell
counts and percentages remained stable in both groups throughout hepatitis C
was generally safe and well-tolerated. There were no serious adverse events or
early discontinuations for this reason in either group. The most common
side-effects were headache, fatigue, pain, nausea, diarrhoea and constipation. There
were no notable changes in serum creatinine or estimated GFR (measures of
kidney function) over time in either group.
concluded that the interferon- and ribavirin-free regimen of sofosbuvir plus
ledipasvir led to SVR12 in 100% of ARV-untreated patients and SVR4 in 100% of
ARV-treated patients with data collection ongoing. Sofosbuvir/ledipasvir was
safely administered in combination with several antiretroviral regimens.
In light of these promising
results, an audience member asked about the prospect of reducing
sofosbuvir/ledipasvir treatment duration to 8 weeks. Osinusi replied that many interferon-free studies have now suggested that
HIV is not a risk factor for poorer response. "If an 8-week duration works
in [HCV] mono-infected patients, I don’t see why it shouldn’t in co-infected
[patients] as well," she said.