Studies show treatment parity among those living with HCV & HCV/HIV
by Larry Buhl
[dropcap]A[/dropcap] press conference at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) offered two main takeaways: that the new generation of oral direct-acting antiviral agents (DAAs) are highly effective and safe, and that doctors can treat HIV-negative patients with hepatitis C and HIV/HCV coinfected patients with the same DAAs, while taking into account any possible interactions with HIV meds.
That conclusion was based on results of two Phase III studies both discussed at the press conference which showed not only exceptional cure rates but that response rates in HIV/HCV coinfected patients as high as for those infected only with HCV in previous trials.
Each phase three study looked at two-drug, twelve-week regimens using DAAs: sofosbuvir (Sovaldi) plus either ledipasvir (the Harvoni coformulation) or daclatasvir (Daklinza). Both studies showed a cure rate of ninety-six percent of HIV/HCV coinfected people with various hepatitis C genotypes.
Susanna Naggie from Duke Clinical Research Center in North Carolina presented results from ION-4, a Phase III trial evaluating Gilead Sciences’s nucleotide HCV NS5B polymerase inhibitor sofosbuvir plus NS5A inhibitor ledipasvir in HIV/HCV coinfected patients.
ION-4 studied 335 coinfected participants in the U.S., Canada, and New Zealand. Eighty-two percent of participants were men, thirty-four percent were black, and the mean age was fifty-two years. Ninety-eight percent had HCV genotype 1. More than half (fifty-five percent) had been previously treated for HCV, three-quarters had unfavorable IL28B gene variants, and twenty percent had compensated cirrhosis.
All participants with HIV were required to be on antiretroviral therapy, either efavirenz (Sustiva), raltegravir (Isentress), or rilpivirine (Edurant), and all with tenofovir/emtricitabine (Truvada). Most had an undetectable HIV viral load.
All participants received 400 mg sofosbuvir plus 90 mg ledipasvir, taken as a once-daily coformulation, for twelve weeks. They were followed for an additional twelve weeks after completing treatment to assess sustained virological response (SVR12), or continued undetectable HCV RNA.
The overall SVR12 rate in this study was ninety-six percent, similar to rates seen in the ION HCV monoinfection studies, and sofosbuvir/ledipasvir was generally safe and well-tolerated.
There was one curious result that Dr. Naggie said could not yet be explained. In a multivariate analysis the only factor that significantly predicted relapse was black race/ethnicity. In fact, all ten who relapsed were black.
[pull_quote_center]racial disparity in treatment failure rates was not seen in the ION monoinfection trials[/pull_quote_center]
Naggie told A&U that racial disparity in treatment failure rates was not seen in the ION monoinfection trials, in which ninety-nine percent of black patients were cured, and that’s why she thinks the race issue in ION-4 could be a fluke. “If the issue were the race of host, we would have seen similar results in the rest of the ION trials. We have to prove it by trying to reproduce the results with another trial with an adequate number of black patients before we can determine what led to [these results].”
At the same conference, David Wyles from the University of California at San Diego presented results from the ALLY-2 trial, which studied sofosbuvir in combination with a different NS5A inhibitor, Bristol-Myers Squibb’s daclatasvir. Daclatasvir is active against a wider range of HCV genotypes than ledipasvir, which is primarily effective against genotype 1. Genotype 1 is most common in the United States and Europe, but different genotypes are common in countries with high HCV rates.
All participants in ALLY-2 received once-daily 400 mg sofosbuvir plus daclatasvir. There were two groups tested: 151 previously untreated patients (including prior use of sofosbuvir) who received the regimen for eight or twelve weeks, and fifty-two treatment-experienced patients all of whom received the twelve-week course.
Participants could either be on ART with undetectable HIV RNA and a CD4 count of at least 100 cells/mm3, or not yet on ART with at least 350 cells/mm3. Median CD4 counts were in the 500-600 cells/mm3 range. Those on ART were permitted to take a wide range of antiretrovirals.
The standard 60 mg daclatasvir dose was adjusted down to 30 mg with ritonavir-boosted HIV protease inhibitors or up to 90 mg with most NNRTIs to account for drug interactions (all doses were combined in the analysis).
Results showed twelve-week SVR rates ninety-six percent for treatment-naive patients and ninety-eight percent for treatment-experienced. But the SVR fell to seventy-six percent for treatment-naive people on an eight-week regimen. These rates were similar for genotype 1 patients and all genotypes together. As with ION-4, treatment was generally safe and well-tolerated. Most patients maintained HIV viral suppression and stable CD4 counts.
Naggie says there is little doubt that HCV monoinfected and HIV/HCV coinfected receive equal benefits from treatment with DAAs. “Now we need to focus on trials that represent people of other countries and more ethnicities and other diseases like autoimmune disease to see if [DAAs] are effective across a wider spectrum of people.” ◊
Larry Buhl is a radio news reporter, screenwriter, and novelist living in Los Angeles. His podcast on employment issues, “Labor Pains,” can be found at www.laborpainspodcast.com.