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Glecaprevir/pibrentasvir is effective for people with HIV/HCV co-infection
Liz Highleyman, 2017-07-26 06:10:00
AbbVie's new pangenotypic regimen combining glecaprevir and pibrentasvir cured almost all HIV-positive people with hepatitis C co-infection in the EXPEDITION-2 study, according to a presentation on Monday at the 9th International AIDS Society Conference on HIV Science (IAS 2017) in Paris.
Glecaprevir/pibrentasvir (Maviret) is expected to be approved by the US Food and Drug Administration in August, and it has received a positive opinion from the scientific committee of the European Medicines Agency (the CHMP) and should receive European Union marketing approval within next few months.
Direct-acting antivirals (DAAs) used in interferon-free regimens can now cure most people with all hepatitis C virus (HCV) genotypes in 12 weeks, and easier-to-treat patients - such as previously untreated individuals with mild liver fibrosis - can usually achieve sustained virological response (SVR) with only 8 weeks of therapy. A shorter course of treatment could potentially improve adherence and reduce cost.
HIV/HCV co-infected people did not respond as well as HIV-negative patients to interferon-based therapy, and therefore this population has historically been considered difficult to treat. However, studies in the DAA era have shown that HIV-positive people generally do as well on interferon-free regimens as those without HIV - though it is important to take into account the potential for drug interactions between DAAs and antiretrovirals - and they are no longer considered a "special population." Yet European and US HCV treatment guidelines currently do not recommend shorter treatment for people with HIV and HCV co-infection.
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, to be marketed under the brand name Maviret.
Studies presented at this year's International Liver Congress showed that glecaprevir/pibrentasvir cured 99% of hepatitis C patients with 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 Europe, the United States and Russia. More than 80 percent 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%); a small number had genotypes 2 or 6.
Sixteen participants (10%) had liver cirrhosis, and most of the rest had absent or mild fibrosis. Nearly 20% were previously treated with interferon and ribavirin, and three had also used sofosbuvir (Sovaldi).
Study participants had well-controlled HIV infection with a median CD4 count of nearly 600 cells/mm3. All but nine 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. Everyone received the study drugs and there was no placebo arm.
Treatment was highly effective, with 98% having 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/pibrentasvir was 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 haemorrhage). 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.
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