The revolution of treatment development with direct acting agents against hepatitis C virus (HCV) is moving faster than a speeding bullet. As it once was for treatment development of HIV, it is dramatic.
Thus, one of many reasons to attend the 19th Conference on Retroviruses and Opportunistic Infections (CROI), held this year in Seattle in March, was the intensity and new data regarding HCV treatment. This was unusual for a conference historically focused on the basic science of HIV.
There is a growing incidence of hepatitis C infection among HIV-positive individuals (co-infection) and it is becoming clear that HCV treatment is complicated. Treatments differ in regards to HCV genotype, therapy for treatment-naive vs. history of treatment failure, and drug-drug interactions for patients with co-infection. HIV specialists are accustomed to these kinds of complex issues while gastroenterologists, busy with endoscopic procedures, and hospital-based infectious disease specialists, with limited office hours, may not be able to tackle the rocketing numbers of patients with HCV infection growing to monumental proportions. With many future agents becoming developed, much heavy lifting treating HCV-infected patients will be left to physicians who manage HIV disease. However, there is a progressive decrease of physicians wanting to specialize in HIV disease treatment.
A poster presented by the Swiss Cohort team showed staggering statistics in regards to the growing hepatitis C epidemic among those infected by HIV. Their investigation of the MSM (men who have sex with men) population excluded intravenous drug users and heterosexuals. Of 3,333 MSM patients followed, the incidence of new HCV infections in 2011 (compared to 1998) increased 18-fold. Identified risk factors were unsafe anal sex, history of syphilis, and chronic hepatitis B infection. Indeed, the take home message for clinicians is the need for increased testing for HCV and for gay men engaged in unsafe sexual practices, the message is beware and exercise prevention; one needn't be engaged in intravenous drug use to become infected.
The "Breakthroughs in HCV Treatment" session began with presentations of studies with telaprevir (Incivek) and boceprevir (Victrelis), both inhibitors of NS3/4A HCV protease. Both won FDA approval in 2011 for use with pegylated interferon and ribavirin in adults with genotype 1 chronic HCV and compensated liver disease. However, neither boceprevir nor telaprevir is licensed for use in HIV/HCV co-infection. At CROI, two co-infection studies were highlighted; both trial designs included combinations with pegylated interferon and ribavirin (P/R), and both included the conventional "futility rules" that have become standard for patients undergoing treatment. Protocols put futility rules in place so that patients who experience viral rebound or those who do not reach rapid declines in hep C RNA (viral load) or undetectability within a specified time frame are discontinued from treatment, avoiding resistance mutations or further side effects with failing treatment. Also discussed were HIV drug interactions, crucial for understanding their use with HIV treatment.
Dr. Douglas Dieterich presented a trial of treatment with telaprevir (TVR) in genotype 1 HCV co-infected patients; genotype 1 is the most common and, unfortunately, the most difficult to treat HCV strain.
Patients were administered telaprevir (750 mg every 8 hrs)+P/R for 12 weeks followed by 36 weeks of P/R alone; in the P/R control group, patients were treated for 48 weeks with P/R alone. Further, the trial was divided into parts A and B. In part A, 13 patients were treated without ART (antiretrovirals); 7 randomized to P/R+TVR and 6 on P/R alone. In part B, 24 patients were on Atripla, 16 treated with P/R+TVR and 8 on P/R alone. Also, 23 patients were on ritonavir-boosted atazanavir (Reyataz/Norvir) with either Truvada (emtricitabine/tenofovir) or Viread/Epivir and of these, 15 were treated with P/R+TVR and 8 with P/R alone.
At 12 weeks post-treatment the overall SVR (sustained virologic response -- indicates treatment success), was 74% in the P/R/TVR-treated patients vs. 45% in controls. There were no HIV treatment failures; three HCV treatment failures occurred -- at week 4 with one patient in each of the Atripla and Reyataz groups and one at week 12 in the Atripla group. Patient discontinuations due to futility rules were more common in the P/R controls (32 vs. 5%) and discontinuations due to adverse events were 8% in the TVR group vs. 0% in the P/R group. The most common side effect was fatigue in both groups (41-42%) with pruritis (itchy skin), nausea, headache, and rash being more common in the TVR treatment groups. No dosage adjustments were necessary except for a higher dose of telaprevir (1,125 mg every 8 hours) required to offset reduced exposure of it with efavirenz (Sustiva, in Atripla).
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