Jürgen Rockstroh from
the University of Bonn presented final combined results from the phase 3 PHOTON
trials, which evaluated a dual oral regimen of the nucleotide HCV polymerase
sofosbuvir plus ribavirin. Sofosbuvir was recently approved in the US and
Europe and its recommended indications are the same for people with HIV
and HCV co-infection and those with HCV alone.
PHOTON-1 was conducted in the US and PHOTON-2 took
place in Europe and Australia. The two studies combined included a total of 497
participants. About 80% were men, most were white and the average age was 48
years. Just under half (46%) had HCV genotype 1, 15% had genotype 2, 33% had
genotype 3 and 6% had genotype 4. Most (81%) were previously untreated for
hepatitis C, about 60% had unfavourable IL28B variants and 15%
had compensated cirrhosis.
The mean CD4 count was again high (605 cells/mm3)
and almost all were on suppressive ART containing tenofovir/emtricitabine plus
efavirenz (Sustiva; 30%), raltegravir
(20%), boosted darunavir (19%), boosted atazanavir (17%), rilpivirine (Edurant; 5%) or other drugs (8%).
All participants received once-daily sofosbuvir plus
ribavirin, with treatment duration determined by genotype:
- Genotype 1: treatment-naive 24 weeks
(n = 226)
- Genotype 2: treatment-naive 12 weeks
(n = 45); treatment-experienced 24 weeks (n = 30)
- Genotype 3: treatment-naive 12 weeks
(n = 42) or 24 weeks (n = 57); treatment-experienced 24 weeks (n = 66)
- Genotype 4: treatment-naive 24 weeks
(n = 31)
SVR12 rates were 81% for treatment-naive patients with
genotype 1 HCV treated for 24 weeks, 89% for treatment-naive patients with genotype
2 HCV treated for 12 weeks, 90% for treatment-experienced patients with genotype
2 HCV treated for 24 weeks, 67% for treatment-naive patients with genotype 3 HCV
treated for 12 weeks, 91% for treatment-naive patients with genotype 3 HCV
treated for 24 weeks, 88% for treatment-experienced patients with genotype 3
HCV treated for 24 weeks and 84% for treatment-naive patients with genotype 4 HCV
treated for 24 weeks.
Among people with genotype 1, SVR12 rates were 65% and
85% for people with subtype 1a, with and without cirrhosis, respectively,
compared to 60% and 67% for people with subtype 1b. This is contrary to most
studies which find higher cure rates for people with subtype 1b, but numbers
here were small.
Among people with genotype 2, SVR12 rates were 100%
for patients with and 88% for those without cirrhosis in both the
treatment-naive 12-week and treatment-experienced 24-week arms.
Among people with genotype 3, SVR12 rates were 67% for
treatment-naive people both with and without cirrhosis treated for 12 weeks.
Among those treated for 24 weeks, cure rates were 100% and 91%, respectively,
for treatment-naive people with and without cirrhosis, and 79% and 95% for
Finally, among people with genotype 4, SVR12 rates
were 88% for those with and 83% for those without cirrhosis.
People with genotype 1 who had cirrhosis had lower
SVR12 rates, as expected. In some comparisons of the other genotypes, people with
cirrhosis had numerically higher cure rates – again contrary to previous
studies – but numbers of people with cirrhosis were too small to draw
statistically valid conclusions.
People with genotype 2 had the same SVR12 rates
whether they were treated for 12 or 24 weeks. Among people with genotype 3,
however, those treated for 24 weeks did better than those treated for the
Among the participants with treatment failure, 70 were
due to post-treatment relapse, three were due to viral breakthrough during
treatment, six withdrew consent and five were lost to follow-up.
The sofosbuvir plus ribavirin regimen was also generally
safe and well-tolerated. In both the 12-week and 24-week arms, 6% experienced
serious adverse events and 3% discontinued therapy for this reason. The most
commonly reported side-effects were again fatigue, insomnia, nausea and headache. About
10% developed moderate anaemia, but fewer than 1% had severe anaemia. Six
people experienced HIV breakthrough during hepatitis C treatment (two of whom
were non-adherent) but none required ART modification. CD4 counts dropped
temporarily – a known effect of ribavirin – but CD4 percentages remained
"Sofosbuvir + ribavirin resulted in high SVR12 rates in
HIV patients coinfected with HCV genotype 1, 2, 3 or 4," the researchers
concluded. "Rates were similar to those in HCV monoinfected
Rockstroh noted that adverse event rates in this study
were "much lower than
anything we saw previously in coinfected patients in the interferon era,"
which gives support to hepatitis C treatment guidelines that no longer separate
people with HCV mono-infection and people with HIV/HCV co-infection.
Anna Lok pointed out that while these results "would have been very
exciting a couple years ago," the field has moved on. A
sofosbuvir/ledipasvir co-formulation is now available (approved and marketed as
Harvoni in the US) that has shown
higher cure rates – including for people with co-infection – and eliminates ribavirin and
suggested that sofosbuvir plus ribavirin "is likely to remain the standard
of care for genotype 2," but for people with other genotypes "adding
another direct-acting antiviral is the way to go," as this may allow shorter
treatment which would have a cost benefit.