- Category: HCV Treatment
- Published on Tuesday, 08 November 2011 00:00
- Written by Liz Highleyman
Adding the hepatitis C virus (HCV) protease inhibitor telaprevir (Incivek) to pegylated interferon plus ribavirin increased virological response rates at 24 weeks for HIV/HCV coinfected patients, researchers reported at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) this week in San Francisco.
Telaprevir -- along with another HCV protease inhibitor, boceprevir (Victrelis) -- was approved by the U.S. Food and Drug Administration in May. Pivotal studies demonstrated that telaprevir plus standard therapy with pegylated interferon/ribavirin was significantly more effective than standard therapy alone.
HIV positive people with hepatitis C tend to experienced more rapid liver disease progression and do not respond as well to interferon-based therapy. This population, therefore, has a pressing need for better HCV treatment.
In a late-breaker poster at the AASLD meeting, Kenneth Sherman from the University of Cincinnati College of Medicine and colleagues presented 24-week data from an ongoing Phase 2 trial comparing telaprevir triple therapy versus standard hepatitis C therapy in HIV/HCV coinfected patients. Prior 12-week results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2011) this past March.
The study had 2 parts. Part A enrolled antiretroviral therapy (ART)-naive people who still had CD4 cell counts high enough that they did not yet need HIV treatment (> 500 cells/mm3). Part B enrolled people with > 300 cells/mm3 on a stable ART regimen containing either efavirenz (Sustiva) or boosted atazanavir (Reyataz), both with tenofovir/emtricitabine (the drugs in Truvada).
The study enrolled 62 participants with hard-to-treat HCV genotype 1 who had not previously been treated for hepatitis C; 60 people who received at least 1 dose of study drugs were included in the analysis. Most (about 85%) were men, the average age was about 45 years, and about half in Part A and 20% in Part B were black. About half in Part A and about 75% in Part B had HCV genotype 1a.
In both parts participants were randomly assigned to receive either telaprevir triple therapy or standard therapy for 48 weeks. Studies of HCV monoinfected patients have shown that many can achieve sustained response with a shorter duration of pegylated/interferon after telaprevir. Since HIV positive people tend to respond more slowly, however, all the coinfected patients in this trial were assigned to receive the full 48-week course, but they stopped treatment if they did not experience an adequate HCV RNA reduction by week 12.
Triple therapy consisted of telaprevir every 8 hours (the usual 750 mg dose if using atazanavir or 1125 mg if using efavirenz, to compensate for a drug interaction) plus 180 mcg/week pegyalted interferon alfa-2a (Pegasys) plus daily ribavirin (800 mg/day fixed dose or 1000-1200 mg/day weight-adjusted doses, depending on study site). Standard therapy consisted of the same doses of pegyalted interferon and ribavirin alone.
Rates of rapid virological response (RVR), or undetectable HCV RNA at week 4, for telaprevir recipients were:
- No ART: 71%;
- Efavirenz regimen: 75%;
- Atazanavir regimen: 60%;
- Overall: 68%.
- In contrast, no one in any group receiving standard therapy achieved RVR.
Rates of complete early virological response (cEVR), or undetectable HCV RNA at week 12, for telaprevir recipients were:
- No ART: 86%;
- Efavirenz regimen: 88%;
- Atazanavir regimen: 67%;
- Overall: 79%.
- cEVR rates with standard therapy were 33%, 25%, 25%, and 27%, respectively.
Rates of undetectable HCV RNA at week 24 for telaprevir recipients were:
- No ART: 86%;
- Efavirenz regimen: 75%;
- Atazanavir regimen: 67%;
- Overall: 71%.
- 24-week response rates with standard therapy were 33%, 50%, 75%, and 55%, respectively.
- HIV RNA remained undetectable in all groups.
- Absolute CD4 cell counts declined from baseline in all groups, although CD4% remained unchanged.
- Overall, people receiving telaprevir triple therapy experienced more side effects than those on pegylated interferon/ribavirin alone.
Adverse events occurring at least 10% more often among telaprevir recipients compared with standard therapy recipients included:
- Pruritis or itching: 39% vs 9%;
- Headache: 37% vs 27%;
- Nausea: 34% vs 23%;
- Skin rash: 34% vs 23%;
- Fever: 21% vs 9%;
- Depression: 21% vs 9%;
- Insomnia: 13% vs 23%.
- Weight loss, however, was significantly less common among telaprevir recipients (11% vs 23%).
- Anemia rates were similar in both groups (13% vs 18%, respectively); 4 patients in total required erythropoietin.
- No cases of severe rash were observed.
- As expected, people taking atazanavir were more likely to develop elevated bilirubin.
- No participants taking no ART or the efavirenz regimen discontinued treatment due to adverse events, but 3 people receiving telaprevir with the atazanavir regimen did so.
"In this interim analysis, higher Week 24 on-treatment responses were seen in chronic genotype HIV/HCV coinfected patients treated with telaprevir/pegylated interferon/ribavirin (71%) compared to pegylated interferon/ribavirin alone (55%)," the researchers concluded.
"Overall safety and tolerability of patients treated with telaprevir combination treatment was comparable to that previously observed in chronic genotype 1 HCV monoinfected patients," they added.
Studies of telaprevir for HIV/HCV coinfected people are ongoing. Further trials will assess whether selected coinfected patients may also benefit from response-guided therapy and shorter treatment duration.
Investigator affiliations: University of Cincinnati College of Medicine, Cincinnati, OH; University of Bonn, Bonn, Germany; Mount Sinai School of Medicine, New York, NY; Hospital Carlos III, Madrid, Spain; Hôpital St Antoine, Paris, France; Vertex Pharmaceuticals Incorporated, Cambridge, MA; Johns Hopkins University School of Medicine, Baltimore, MD.
KE Sherman, JK Rockstroh, DT Dieterich, et al. Telaprevir Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Coinfected Patients: 24-Week Treatment Interim Analysis. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract LB-8.
Vertex Pharmaceuticals. Positive Interim Data From a Phase 2 Study of INCIVEK(TM) (telaprevir) Combination Therapy in People Co-Infected with Hepatitis C and HIV Presented at The Liver Meeting. Press release. November 5, 2011.