In a study sponsored by Gilead Sciences called Astral-5, researchers in the United States tested the fixed-dose combination of sofosbuvir + velpatasvir (sold as Epclusa) in 106 people who were co-infected with hepatitis C virus (HCV) and HIV. Overall, 95% of participants (99 out of 104) were cured. The combination of sofosbuvir + velpatasvir was effective against genotypes present in the study (genotypes 1 through 4). Side effects were mostly of mild-to-moderate intensity.

Study details

The average profile of participants upon entering the study was as follows:

• age – 54 years
• 91% men, 8% women
• 18% had severe scarring of the liver (cirrhosis) but no symptoms of this
• 29% had unsuccessfully attempted treatment in the past
• HCV viral load – 2 million IU/mL
• CD4+ cell count – 600 cells/mm³
• all participants were taking anti-HIV medicines and their HIV viral loads were less than 50 copies/mL
• no participant was taking efavirenz (Sustiva, Stocrin and in Atripla), as this anti-HIV drug significantly reduces the amount of velpatasvir in the blood

The distribution of genotypes was as follows:

• genotype 1a – 66 people
• genotype 1b – 12 people
• genotype 2 – 11 people
• genotype 3 – 12 people
• genotype 4 – five people

Cure rates

Overall, so far 95% of participants (99 out of 104) were cured (final data from two participants are pending).

Cure rates distributed by genotype are as follows:

• genotype 1a – 95% (62 out of 65) cured; two participants relapsed
• genotype 1b – 92% (11 out of 12) cured; one person stopped visiting the study clinic
• genotype 2 – 100% (11 out of 11) cured
• genotype 3 – 92% (11 out of 12) cured; one participant prematurely left the study
• genotype 4 – 100% (four out of four) cured

All participants who had cirrhosis were cured.

HCV resistance testing

At the start of the study before participants began taking sofosbuvir + velpatasvir, Gilead tested blood samples from 101 participants for the presence of HCV that could, in theory, have the ability to resist the effects of treatment. Technicians found that a total of 12 participants (12%) had HCV that could resist an inhibitor of NS5A. However, all 12 of these people were cured.

Side effects

Although 71% of participants reported side effects, the vast majority of these were graded mild to moderate by researchers. However, 8% of participants experienced more intense side effects.

Common side effects included the following:

• lack of energy/unexpected tiredness – 25%
• headache – 13%
• bone/joint pain – 8%
• diarrhea – 8%
• problems sleeping – 7%
• nausea – 7%

No one died during the study.

Nineteen people developed highly abnormal lab test results. This was most commonly elevated levels of the waste product bilirubin in the blood, which occurred in participants who were taking the anti-HIV medicines atazanavir (Reyataz) and ritonavir (Norvir).

Participants who were taking the anti-HIV drug tenofovir (Viread and in Truvada) together with a protease inhibitor or the boosting agent cobicistat experienced a modest decrease in the functioning of their kidneys. This was assessed with eGFR (estimated glomerular filtration rate).

Key points

Treatment with 12 consecutive weeks of sofosbuvir + velpatasvir resulted in a high rate of cure: 100% of participants with cirrhosis and 97% of participants whose past therapy failed were cured.

Sofosbuvir + velpatasvir was generally safe.

—Sean R. Hosein

REFERENCE:

Wyles D, Brau N, Kottilil S, et al. Sofosbuvir and velpatasvir for 12 weeks in patients co-infected with HCV and HIV-1: the Astral-5 study. The International Liver Congress, 13-17 April 2017, Barcelona, Spain. Abstract PS-104.