Sofosbuvir (GS-7977) belongs to a class of anti-hepatitis C virus (HCV) drugs called nucleotide analogues. Sofosbuvir interferes with a protein needed by HCV and reduces the production of HCV from infected cells.
In lab experiments with cells, sofosbuvir can suppress several different strains, or genotypes, of HCV. No serious side effects have been reported from several small Phase I and Phase II clinical trials that have enrolled 450 HCV-monoinfected people (HCV infection alone) who were exposed to the drug for up to 12 weeks. Dosing with sofosbuvir is just one pill daily and it can be taken with or without food.
In clinical trials of HCV monoinfection, sofosbuvir, when used with interferon and the broad-spectrum drug ribavirin, has relatively high cure rates (greater than 88%).
Sofosbuvir is completing Phase III clinical trials as part of combination therapy for HCV monoinfection.
To understand the impact of sofosbuvir in HCV-HIV co-infected people, researchers in Puerto Rico conducted a short clinical trial. The results showed that sofosbuvir is safe. The next step is combination therapy for people with HCV-HIV co-infection.
Researchers recruited 30 co-infected participants with the following average profile:
- 25 men, 5 women
- age – 53 years
- HCV viral load – 3.7 million copies/ml
- participants were infected with different genotypes of HCV, including 1a, 1b, 2, 3 and 4
- CD4+ count – 600 cells
- HIV viral load was less than 50 copies/ml in all but one participant, in whom it ranged between 50 and 100 copies/ml
Participants were taking different anti-HIV regimens, as follows:
- Atripla (efavirenz + tenofovir + FTC)
- efavirenz (Sustiva) + AZT + 3TC
- atazanavir (Reyataz) + ritonavir (Norvir) + tenofovir + 3TC
- darunavir (Prezista) + ritonavir + tenofovir + FTC
- raltegravir (Isentress) + tenofovir + FTC
Participants received sofosbuvir at a dose of 400 mg once daily for seven days. At the end of this time they were monitored for seven more days.
Sofosbuvir monotherapy dramatically reduced HCV viral load by more than 4 logs. Its antiviral activity continued for several days after participants took their final dose.
The potency of sofosbuvir was demonstrated in the study when 50% of participants developed a viral load less than 25 IU/ml—the lower limit of detection of the viral load assay used in this study.
The response to sofosbuvir was similar regardless of the genotype of HCV infection.
Decreases in HCV viral load were seen across all HIV treatment regimens.
These decreases in HCV viral load are similar to those seen in HCV monoinfection.
All adverse effects, potentially caused by sofosbuvir, were mild, except in one case where one participant’s hemorrhoids became worse.
Other key findings included the following:
- No severely abnormal changes to lab test results, including CD4+ cell counts and HIV viral load, were seen.
- There were no differences in results when they were analysed by race.
In the future
Many clinical trials of sofosbuvir in HCV monoinfection are underway. It is likely that at least initially this drug will be approved as part of triple therapy with both interferon and ribavirin. However, interferon-free sofosbuvir regimens are being tested. In the U.S., a large clinical trial of sofosbuvir + ribavirin is currently recruiting HCV-HIV co-infected participants who have HCV genotypes 2 or 3.
—Sean R. Hosein
- Rodriguez-Torres M, Gonzales M, Rodriguez J, et al. HIV/HCV co-infected and HCV monoinfected patients have similar early hepatitis C viral kinetics with the potent HCV nucleotide polymerase inhibitor sofosbuvir. In: Program and abstracts of the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, 9-12 September 2012. San Francisco, California. Abstract H-1921a.
- Barreiro P, Vispo E, Poveda E, et al. Hepatitis C therapy - highlights from EASL 2012. Clinical Infectious Diseases. 2012; in press.