IAS 2017: Glecaprevir/ Pibrentasvir Effective for People with HIV/HCV Coinfection

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AbbVie's new 8-week pangenotypic regimen combining glecaprevir and pibrentasvir cured almost all HIV-positive people with hepatitis C coinfection in the EXPEDITION-2 study, according to a presentation at the 9th International AIDS Society Conference on HIV Science (IAS 2017) last month in Paris.

Glecaprevir/pibrentasvir was approved by the U.S. Food and Drug Administration on August 3, to be marketed under the brand name Mavyret. It will be sold as Maviret in the European Union.

Direct-acting antivirals (DAAs) used in interferon-free regimens can now cure most people with all hepatitis C virus (HCV) genotypes in 12 weeks. But a shorter course of therapy may work well for easier-to-treat patients -- such as previously untreated people with mild liver fibrosis -- and this could potentially improve adherence and reduce cost.

HIV-positive people did not respond as well as HIV-negative patients to interferon-based therapy for hepatitis C, and they were historically considered "difficult to treat." Studies in the DAA era have shown that HIV-positive people generally do as well as those without HIV -- though it is important to take into account potential drug interactions between DAAs and antiretrovirals -- but U.S. and European guidelines currently do not recommend shorter treatment for people with HIV/HCV coinfection.

Karine Lacombe of Saint-Antoine Hospital in Paris presented findings from AbbVie's Phase 3 EXPEDITION-2 trial, which evaluated an 8-week regimen of glecaprevir/pibrentasvir for people with both HIV and hepatitis C.

Glecaprevir is an HCV NS3/4A protease inhibitor and pibrentasvir is an NS5A inhibitor. Both are pangenotypic, or active against all HCV genotypes. The two drugs have been coformulated in a once-daily combination pill.

Studies presented at this year's International Liver Congress showed that glecaprevir/pibrentasvir cured 99% of hepatitis C patientswith multiple HCV genotypes, as well as 95% of people with hard-to-treat genotype 3.

EXPEDITION-2 enrolled 153 HIV-positive people with chronic hepatitis C in the U.S., Europe, and Russia. More than 80% were men and the median age was approximately 45 years. About two-thirds had HCV genotype 1 (mostly with harder-to-treat subtype 1a), followed by genotypes 3 (17%) and 4 (11%); only a small number had genotypes 2 or 6.

A total of 16 participants (10%) had liver cirrhosis, and most of the rest had absent or mild-to-moderate fibrosis (stage F0-F2). Nearly 20% were previously treated with interferon and ribavirin, and 3 people had also used sofosbuvir (Sovaldi).

Study participants had well-controlled HIV infection with a median CD4 count of nearly 600 cells/mm3. All but 9 were on antiretroviral therapy, and about three-quarters of treated patients were taking the integrase inhibitors raltegravir (Isentress) or dolutegravir (Tivicay), which were shown to have minimal interactions with glecaprevir and pibrentasvir.

Participants without cirrhosis received glecaprevir/pibrentasvir for 8 weeks, while those with cirrhosis were treated for 12 weeks -- the same durations tested in HIV-negative people. Everyone received the study drugs; there was no placebo arm.

Treatment was highly effective, with 98% of participants overall achieving sustained virological response, or continued undetectable HCV RNA at 12 weeks post-treatment (SVR12). The cure rate rose to 99%, with no virological failures, for people without cirrhosis who were treated for 8 weeks.

A single patient with HCV genotype 3 and cirrhosis, who reported less than complete (85%) adherence, experienced virological failure during treatment. Another participant had missing data at 12 weeks post-treatment, but returned for care at 24 weeks post-treatment and was found to be cured.

Glecaprevir/pibrentasvirwas generally safe and well-tolerated. Adverse events were similar to those seen in studies of HIV-negative people. One participant with cirrhosis stopped treatment early due to an adverse event that was not considered drug-related (stroke and brain hemorrhage). The most common adverse events were fatigue, nausea, headache, and nose and throat inflammation.

"These results suggest that the glecaprevir/pibrentasvir regimen could be the first 8-week, pangenotypic treatment option for HCV/HIV-1 coinfected patients without cirrhosis," the researchers concluded.

"I think that it’s a very attractive strategy," Lacombe said. "There are very few drug-drug interactions and very few antiretrovirals are contraindicated. Some are not recommended, but with drug monitoring it can be used in patients who are heavily treated for HIV. I think it's a very promising combination even in patients who have failed previous treatment."

8/7/17

Source

J Rockstroh, K Lacombe, R Viani, et al. Efficacy and safety of glecaprevir/pibrentasvir in patients co-infected with hepatitis C virus and human immunodeficiency virus-1: the EXPEDITION-2 study. 9th International AIDS Society Conference on HIV Science.Paris, July 23-26, 2017. Abstract MOAB0303.