Top 10 HIV/AIDS-Related Clinical Developments of 2011
December 1, 2011
Hepatitis C (HCV) therapeutics is entering a revolution akin to that seen with the first protease inhibitors for the treatment of HIV infection. Two new, oral HCV protease inhibitors, Incivek (telaprevir) and Victrelis (boceprevir), were approved for the treatment of those mono-infected with HCV genotype 1. The approval of these so-called "direct-acting antivirals" (DAAs) has created a renewed awareness about HCV and has raised the hopes of those infected -- including patients who harbor both HIV and HCV -- that the days of interferon are numbered.
The addition of either of these new HCV drugs to a standard regimen of interferon and ribavirin (brand names: Copegus, Rebetol, RibaTab, Ribasphere) almost doubles the rate of HCV cure in the mono-infected, but there are few data regarding their use in coinfected patients. It is known that patients with HIV and HCV do not respond as well to standard HCV therapy. Further, there is the potential for significant drug-drug interactions between ART and both Incivek and Victrelis.
Mark Sulkowski from Johns Hopkins and colleagues conducted the most important study to date that addresses the use of a DAA for coinfected persons.15 One hundred HCV treatment-naive patients with HIV coinfection were randomized 2:1 to Victrelis 800 mg three times a day plus standard therapy of 1.5 mcg/kg/week pegylated interferon alfa-2b (brand name: PEG-Intron) and 600-1,400 mg/day weight-adjusted ribavirin versus standard therapy alone.
For those in the experimental arm, Victrelis was added to pegylated interferon and ribavirin after a four-week lead-in for 48 total weeks of therapy. Those with detectable HCV RNA and less than a 2-log10 decline in HCV viral load at week 12, or detectable HCV RNA at week 24, stopped treatment given data suggesting very poor likelihood of response.
The participants were mostly male and white, and two thirds had genotype 1a. All were receiving ART with HIV-RNA levels less than 50 copies/mL and CD4+ cell counts of at least 200 cells/µL. ART was limited to two modern-era NRTIs plus a boosted protease inhibitor, given previous data demonstrating a reduction in Victrelis levels when co-administered with Sustiva.
At 24 weeks of overall therapy, over 70 percent of those in the Victrelis arm had undetectable HCV-RNA levels compared to 34 percent of those assigned standard therapy alone. Rates of complete early virological response (cEVR) at week 12 were 59 percent versus 26 percent, respectively. Further, Victrelis was generally well-tolerated, although those assigned this drug had more fever, anorexia, vomiting, headache, altered taste and neutropenia. Overall, 14 percent in the Victrelis arm and 9 percent in the standard-therapy-alone arm discontinued therapy due to adverse events.
The Bottom Line
New HCV therapies are a big deal for the millions of people infected with HCV, as well as for the third who are coinfected with HIV. Low response rates combined with the agony of interferon/ribavirin have prevented many with and without HIV from attempting HCV treatment, but with a greater chance for cure, many are more willing to give HCV treatment a try.
Before taking such a plunge, people with HIV infection and their providers need additional data on the safety and efficacy of both Victrelis and Incivek in coinfected patients. This small, but impressive, study provides reassurance. Another, even smaller, study of Incivek found similarly high response rates in coinfected participants.16
There are still questions about drug interactions that need to be worked out and there are ongoing discussions regarding which patients are most appropriate to treat now versus later. Most every pharmaceutical company has an HCV drug or two in its pipeline and some of these may even be able to be combined into an interferon-free regimen. Therefore, with the possibility of newer, potentially more potent and better-tolerated therapies in the offing and the possibility of cross-resistance across HCV protease inhibitors, use of these first DAAs should be judicious. For those patients with less inflammation and fibrosis on liver biopsy, waiting for the next generation of HCV drugs seems prudent. Those with more advanced evidence of liver disease may not have the luxury of waiting two or more years for better therapies to arrive and for these patients Victrelis and Incivek make more sense.
There are a number of studies of both drugs starting up in HIV/HCV-positive patients, including a new ACTG study of Victrelis. This is an exciting time for HCV therapy and, after having pitifully few options to offer our patients, it will be gratifying to be able to cure more of our patients of HCV.
This article was provided by TheBody.
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