The Time to Test and Treat for HCV Is Now

Here is compelling reason why every MD needs to test his or her patients for HCV, and get them into therapy as soon as possible.

Now is the time to get tested and treated for HCV.

This was one of the main messages at multiple sessions today at the 2015 CROI in Seattle. That advice is especially true if the HCV-infected individual is older, co-infected with HIV, has more advanced fibrosis or cirrhosis, or has previously failed therapy with (ie, null responder to) pegylated interferon and ribavirin. Leaving aside the issue of cost, the already-approved, or soon-to-be-approved, directly acting agents (DAAs), when used in 2- or 3-drug combinations, result in 95% to 100% sustained virologic response rates (SVRs) at 12 or 24 weeks. And these impressive cure rates are holding up in the most difficult-to-treat populations, including the ones that I mentioned at the beginning of this paragraph.

The CDC now recommends that all persons born between 1945 and 1965 get tested for HCV.

In the US, there currently are 3 FDA-approved regimens that use DAAs. One other (daclatasvir) is likely to get approval soon. Briefly, these drugs are or will be approved in combination with other anti-HCV drugs (either other DAAs or ribavirin or pegylated interferon plus ribavirin) across a range of HCV genotypes and risk groups:

1. Viekara Pack is a combination of ombitasvir (NS5A inhibitor) plus paritaprevir boosted with ritonavir (NS3/4A inhibitor) plus dasabuvir (NS5B) inhibitor, usually with ribavirin, for a 12- to 24-week course of therapy for those with genotypes 1a or 1b (the most frequently found genotypes in the US).

2. Sofosbuvir (NS5B inhibitor) can be used with ribavirin with or without pegylated interferon (depending on HCV genotype) for 12 to 24 weeks. It has activity against genotypes 1, 2, 3, and 4. It is also approved in combination with ledipsavir (NS5A) inhibitor for an 8- to 12-week course of therapy in persons with HCV genotype 1 and marketed under the name of Harvoni.

3. Daclatasvir (NS5A inhibitor), approved in Japan, Europe (August 2014), and Brazil, is currently under review by the US FDA. It has activity against HCV genotypes 1, 2, 3, and 4, and typically is combined with sofosbuvir. It seems especially useful in persons with cirrhosis.

What we learned today, in a session titled, “Curing HCV: Mission Accomplished,” should prompt every MD to test his or her patients for HCV, and get them into therapy as soon as possible. Specifically:

1. In a presentation from the CDC, in collaboration with Quest Diagnostics, 3.7% of unique blood samples submitted from sites across the US between 2010 and 2013 tested positive for HCV.¹ That prevalence rate is 7 times the estimated prevalence of HIV in the US, and it is likely that over half of the 273,000 persons represented were previously unaware of their HCV status. More important, half of all specimens from persons born between 1945 and 1965 that tested positive for HCV were believed to be from those with severe fibrosis or cirrhosis, and represented 80% of all samples in the severe fibrosis or cirrhosis categories (by FIB-4 scoring). The CDC now recommends that all persons born between 1945 and 1965 get tested for HCV.

2. Viekira Pack used in HIV/HCV co-infected persons with genotypes 1a or 1b for 12 to 24 weeks resulted in SVR rates of 96% to 100%.²

3. In the most compelling presentation of the session, Cindy Zahnd, MD, from the University of Bern, Bern, Switzerland, showed modeling data that delaying treatment with DAAs in HIV/HCV co-infected persons resulted in a substantially higher predicted death rate.³ Specifically, if an HIV/HCV co-infected person is treated within the first year of diagnosis of HCV, only 3% were projected to ultimately die of liver-related complications: this compares with 5%, 10%, and 25%, if treatment is started at fibrosis stage F2, F3, and F4, respectively.

4. Both daclatasvir plus sofosbuvir⁴(ALLY-2 Study) and ledipsavir plus sofosbuvir (Harvoni) (ION-4 Study)⁵when used for 12 weeks in HIV/HCV co-infected persons resulted in SVR rates >95%. In the ALLY-2 trial, essentially all antiretrovirals were allowed to be used. In that same trial, 8 weeks of therapy gave only a 76% SVR rate.

We have the drugs available to cure HCV. Efforts now need to turn to identifying those infected and getting them into treatment.

References:

1. Klevens M, Huang X, Yeo AE, et al. The Burden of Liver Disease Among Persons With Hepatitis C in the United States. Abstract 145; 2015 CROI; Seattle; 23 – 26 February 2015.
2. Eron JJ, Trinh R, Lalezari J, et al. High SVR Regardless of Time to Suppression With ABT-450/r/Ombitasvir & Dasabuvir+RBVâ¨David Wyles. Abstract 147; 2015 CROI; Seattle; 23 – 26 February 2015.
3. Zahnd C, Salazar-Vizcaya LP, Dufour J-F, et al. Impact of Deferring HCV Treatment on Liver-Related Events in HIV+ Patients. Abstract 150; 2015 CROI; Seattle; 23 – 26 February 2015.
4. Wyles D, Ruane P, Sulkowski, M, et al. Daclatasvir in Combination With Sofosbuvir for HIV/HCV Coinfection: ALLY-2 Studyâ¨David Wyles. Abstract 151LB; 2015 CROI; Seattle; 23 – 26 February 2015.
5. Naggie S, Cooper C, Saag MS, et al. Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected With HCV and HIV-1. Abstract 152LB; 2015 CROI; Seattle; 23 – 26 February 2015.