Gilead’s Pangenotypic HCV Combo Safe With Most HIV Antiretrovirals

Gilead’s forthcoming combination hepatitis C therapy, sofosbuvir/velpatasvir, can be safely used concurrently with most antiretroviral regimens for HIV, according to a study presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2016) in February.

 

Erik Mogalian, a scientist at Gilead Sciences, and his colleagues analyzed drug–drug interactions between sofosbuvir/velpatasvir and HIV regimens containing antiretrovirals boosted with either ritonavir or cobicistat. These boosters interfere with liver enzymes that process drugs, so they are most prone to interactions.

 

Five cohorts, each with 24 to 30 participants, were allocated to receive the following regimens, all in combination with 400/100 mg sofosbuvir/velpatasvir:

 

1. Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (TAF) (Genvoya)

2. Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (TDF) (Stribild)

3. Atazanavir (Reyataz) 300 mg + ritonavir 100 mg + emtricitabine/TDF (Truvada)

4. Darunavir (Prezista) 800 mg + ritonavir 100 mg + emtricitabine/TDF

5. Lopinavir/ritonavir (Kaletra) + emtricitabine/TDF

 

The investigators measured plasma concentrations of sofosbuvir, its main metabolite GS-331007, velpatasvir and the antiretrovirals over time. Although there were some pharmacokinetic changes—such as a doubling of velatasvir levels in the atazanavir cohort, and a modest (20%-40%) increase in tenofovir levels in the TDF cohort, none of the changes were significant enough to require adjustments. Treatment was generally safe and well tolerated.

 

This is another boost for the investigational combination, which is the first pangenotypic HCV therapy. “Many of the current direct-acting antiviral therapies for hepatitis C have drug–drug interactions with HIV medications,” said Imtiaz Alam, MD, the director of the Austin Hepatitis Center, in Texas, in an interview with SPC. “This combination can be safely used with most common antiretrovirals for HIV. It also requires only 12 weeks of therapy in most patients, including cirrhotics. I think this drug advances us into the next level of care for patients.”

 

Data from the Phase III ASTRAL studies, presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2015 and published in The New England Journal of Medicine, showed that 98% of patients across the six genotypes achieved sustained virologic response (SVR) after 12 weeks on sofosbuvir/velpatasvir (N Engl J Med 2015;373[27]:2599-2607; 2015;373[27]:2608-2617). Genotype 1 to 6 patients with decompensated cirrhosis treated with sofosbuvir/velpatasvir and ribavirin achieved 94% SVR at 12 weeks (N Engl J Med 2015;373[27]:2618-2628).

 

Assuming that the FDA approves sofosbuvir/velpatasvir later this year (the target Prescription Drug User Fee Act date is in June), Dr. Alam said he expects that ledipasvir/sofosbuvir (Harvoni, Gilead) will remain the treatment of choice for HCV type 1, while sofosbuvir/velpatasvir will become the primary option for genotypes 2 to 6. “Merck’s Zepatier [elbasvir/grazoprevir] will continue to have the advantage in treating patients with renal failure and those on acid-reducing medications,” he said.