AIDS 2014: Sofosbuvir + Ribavirin Cures More Than 80% of HIV/HCV Coinfected People


An interferon-free regimen of sofosbuvir (Sovaldi) plus ribavirin for 24 weeks led to sustained virological response in 84% to 89% of HIV positive chronic hepatitis C patients with HCV genotypes 1, 2, 3, or 4, according to results from the PHOTON-2 study presented at the 20th International AIDS Conference in Melbourne, Australia. Cure rates were lower, however, for genotype 1a patients with liver cirrhosis.

People with HIV/HCV coinfection experience more rapid liver disease progression than people with hepatitis C alone and do not respond as well to interferon-based therapy. Direct-acting antivirals that target different steps of the HCV lifecycle offer the prospect of shorter treatment, fewer side effects, and higher cure rates for HIV/HCV coinfected as well as HCV monoinfected patients.

Jean-Michel Molina from University of Paris Diderot presented data from the phase 3 PHOTON-2 trial, which included 274 coinfected patients in Europe and Australia. Most (81%) were men and the mean age was 47 years. The most common HCV genotypes were 1 (41%) and 3 (39%), followed by 4 (11%) and 2 (9%). Most genotype 1 patients had harder-to-treat subtype 1a.

Most participants (80%) had not been treated previously for hepatitis C. Overall, 20% had cirrhosis (13% for previously untreated people, rising to 45% for treatment-experienced). Nearly half had the favorable IL28B CC gene variant.

Almost all patients were on stable suppressive antiretroviral therapy for HIV and the mean CD4 T-cell count was nearly 600 cells/mm3. The most commonly used antiretrovirals were efavirenz (Sustiva, also in the Atripla coformulation) at 25%, raltegravir (Isentress) at 23%, ritonavir-boosted darunavir (Prezista) at 21%, and boosted atazanavir (Reyataz) at 17%. All patients used a NRTI combination of tenofovir and emtricitabine (the drugs in Truvada). Early studies found no clinically relevant drug-drug interactions between sofosbuvir and these antiretrovirals, and sofosbuvir is already approved in the U.S. and Europe for HIV/HCV coinfected patients.

All participants received Gilead Sciences' nucleotide HCV polymerase inhibitor sofosbuvir (400 mg once-daily) plus ribavirin (weight-based 1000-1200 mg/day). A small number of previously untreated patients with HCV genotype 2 (n=19) were treated for 12 weeks, while all treatment-experienced people and everyone with harder-to-treat genotypes 1 or 4 were treated for 24 weeks.


  • Sustained virological response rates at 12 weeks after completing treatment (SVR12) were 85% for people with genotype 1, 88% for those with genotype 2, 89% for genotype 3, and 84% for genotype 4.
  • Relapse rates were 13%, 8%, 9%, and 16%, respectively.
  • 1 genotype 3 patient experienced viral breakthrough during treatment.
  • Among patients with HCV genotype 1, response rates were higher for non-cirrhotic patients (88% overall, 87% for subtype 1a, and 100% for subtype 1b) compared to those with cirrhosis (65%, 62%, and 75%, respectively).
  • Presence of cirrhosis was the only significant risk factor for poorer response in a multivariate analysis.
  • For people with other genotypes, cirrhosis had less impact, although the effect was a bit larger for treatment-experienced compared to treatment-naive patients with genotypes 2 or 3.
  • Response rates did not differ significantly between HCV subtypes 1a and 1b, but the number of people with the latter type was small.
  • Likewise, there were too few people not taking antiretroviral therapy to permit a comparative analysis.
  • Looking at HIV-related outcomes, 4 people experienced intermittent low-level HIV viral load, though none required modification of their antiretroviral regimen.
  • Absolute CD4 cell counts increased temporarily during hepatitis C treatment, but CD4 percentages remained stable.
  • Sofosbuvir plus ribavirin was generally safe and well tolerated.
  • 6 people experienced serious adverse events and 3 stopped treatment early due to adverse events.
  • The most frequent side effects among patients treated for 24 weeks were fatigue (20%), insomnia (17%), headache (16%), nausea (15%), and diarrhea (11%). 
  • 1 in 5 patients developed grade 3-4 laboratory abnormalities, most commonly elevated bilirubin among people taking atazanavir.
  • While 10% of participants developed low hemoglobin levels -- a known side-effect of ribavirin -- only 1 had severe anemia.

"Sofosbuvir + ribavirin resulted in high SVR12 rates in HIV patients coinfected with HCV genotype 1, 2, 3, or 4," the PHOTON-2 investigators concluded. "Sofosbuvir was well tolerated, with a low rate of treatment discontinuations due to adverse events."

Results from the PHOTON-1 study were published this week in the Journal of the American Medical Association. This study evaluated the same regimens in HIV/HCV coinfected patients, but it was conducted in the U.S. and had a different genotype distribution that allowed for other subgroups comparisons. Just over half had HCV genotype 1 (79% with 1a) while the remainder were roughly evenly split between genotype 2 and 3.

As previously reported at this year's Retrovirus Conference, the overall SVR12 rate for genotype 1 patients was 76%. Among those with genotype 2, response rates were similar for treatment-naive patients treated for 12 weeks and treatment-experienced patients treated for 24 weeks (88% and 92%, respectively). Among those with genotype 3, however, previously untreated patients taking the shorter duration had a lower response rate (67% vs 94%).

The response rates in the PHOTON trials are not particularly impressive compared to the 90%-100% SVR12 rates seen in several other recent interferon-free studies.

Sofosbuvir works better when combined with other direct-acting antivirals such as the NS5A inhibitors ledipasvir or daclatasvir (Daklinza), which are expected to be approved soon. A disadvantage of ledipasvir is that it does not have potent activity against HCV genotypes 2 or 3.

Molina suggested that sofosbuvir plus ribavirin may be a good option for genotype 2 or 3 coinfected patients without cirrhosis. "Ribavirin is generic," he noted, and this combination "might be attractive in places where you don't have access to all the new drugs."

At a separate session discussing the hepatitis C treatment revolution and how to make recent advances available worldwide, Andrew Hill of Liverpool University and others noted that pan-genotypic drugs -- those that work against multiple HCV genotypes -- could potentially mean we will not need genotype testing, which would lower the overall cost of care.



JM Molina, C orkin, DM Iser, et al. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotypes 1, 2, 3 and 4 infection in patients co-infected with HIV (PHOTON-2). 20th International AIDS Conference. Melbourne, Australia, July 20-25, 2014. Abstract MOAB0105LB.

MS Sulkowski, S Naggie, J Lalezari, et al. Sofosbuvir and Ribavirin for Hepatitis C in Patients with HIV Coinfection. JAMA 312(4):353-361. July 23/30, 2014.

MS Saag. Quantum Leaps, Microeconomics, and the Treatment of Patients With Hepatitis C and HIV Coinfection (Editorial). JAMA312(4):347-348. July 23/30, 2014.

Other Source

JAMA Network. Combination Treatment for Hepatitis C Associated With Favorable Response Among Patients With HIV. Press release. July 19, 2014.