Nearly three-quarters of HIV/HCV co-infected patients in the French HEPAVIH cohort achieved end-of-treatment virological response to hepatitis C treatment with telaprevir plus pegylated interferon/ribavirin, even though one-third had potential contraindications to this type of therapy, according to a report at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) this month in Kuala Lumpur.
People with HIV experience more rapid liver disease progression, on average, than people with hepatitis C virus (HCV) alone, and generally do not respond as well to interferon-based therapy. This population has an urgent need for better treatment options, but adding the HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivo or Incivek) can increase the risk of side-effects and drug-drug interactions with antiretrovirals for HIV.
Dominique Salmon from Cochin Hospital in Paris and fellow investigators with the ANRS CO13 HEPAVIH cohort study looked at treatment access and outcomes among co-infected patients in a 'real-life' clinical practice setting. In clinical trials triple therapy with boceprevir or telaprevir improved response rates by approximately 30% over pegylated interferon/ribavirin alone, she noted, but trials often have restrictive entry criteria that exclude many people who need treatment in the real world.
The prospective HEPAVIH cohort included 1324 co-infected individuals with genotype 1 HCV who were followed at 24 clinical centres in France between January 2011 and June 2013. The researchers compared outcomes among 320 eligible patients – 114 (36%) who started triple therapy and 206 (64%) who did not – looking at contraindications, early treatment response and adverse events.
Participants, with an average age of about 48 years, had well controlled HIV: 85% had undetectable HIV RNA and the median CD4 count was 555 cells/mm3. About 70% had harder-to-treat HCV subtype 1a. Patients who were treated had more severe fibrosis. Among people who started triple therapy, 30% had liver cirrhosis and 71% were non-responders to prior hepatitis C treatment. Among those who did not start therapy, 14% had cirrhosis and only 25% had been previously treated.
Looking at potential contraindications, the most common was psychiatric conditions, reported by 23% of those who started triple therapy and 26% who did not. This is considered a barrier to treatment because interferon can cause or worsen depression and other mental health problems.
The next most common reasons for not starting treatment were current active drug use (reported by 9% of non-starters), heavy alcohol consumption (5%) and use of non-compatible antiretroviral drugs likely to interact with HCV medications. One active drug user and two people on incompatible antiretrovirals started triple therapy anyway. About 3% of both starters and non-starters had decompensated cirrhosis or liver cancer. Anaemia and low platelet counts were uncommon in both groups.
Overall, 34% of people who started triple therapy had at least one contraindication compared with 42% of non-starters – not a significant difference.
Among those who started triple therapy, 80 patients (70%) did so outside a clinical trial. Most used telaprevir (71% overall, 84% outside trials), followed by boceprevir (21% overall, 16% outside trials) and other investigational direct-acting antivirals (nine patients, all in trials). All were on combination antiretroviral therapy, with raltegravir (Isentress) and atazanavir (Reyataz) being the most commonly used drugs.
Salmon did not describe the specific hepatitis C regimens, but telaprevir triple therapy is usually taken for 12 weeks, followed by pegylated interferon/ribavirin alone for up to 36 more weeks depending on early response, with a full 48-week course recommended for people with HIV. Boceprevir triple therapy lasts for up to 48 weeks, again with a long course recommended for hard-to-treat patients including those with HIV.
After 4 weeks on treatment 69% of telaprevir recipients experienced rapid virological response, 80% still had undetectable HCV RNA at the end of the 12-week course of triple therapy and 74% remained undetectable at week 24. Boceprevir recipients responded more slowly, with only 20% having undetectable HCV at week 4, rising to 60% at both weeks 12 and 24. Salmon noted that these response rates were in on the same order as those seen in phase 3 trials.
Response rates varied based on known predictive factors. Among telaprevir recipients, 24-week virological response rates were 82% for treatment-naive patients, 80% for previous relapsers and 68% for prior non-responders. Those with HCV subtype 1b responded better than those with 1a (90% vs 69%), as did people without cirrhosis compared with cirrhotics (77% vs 67%). Patient numbers were too small to make meaningful comparisons among boceprevir recipients.
Turning to tolerability, the most common side-effect was anaemia (haemoglobin <9g/dL), seen in 35% of telaprevir recipients and 20% of boceprevir recipients. Three people used erythropoietin (EPO) and nine required blood transfusions. In the telaprevir group 16% developed skin rash and 8% reported anal pruritis or itching, neither of which was reported by boceprevir recipients.
Overall, one-quarter of participants stopped treatment prematurely, most often due to non-response (67% of telaprevir discontinuations and 80% of boceprevir discontinuations). Six patients stopped due to various adverse events, including two cases of severe anaemia in the telaprevir group.
"Triple therapy was started despite potential contraindications to treatment, mainly psychiatric disorders, present in 34% of treated patients," the researchers summarised. "On the contrary, non-treated patients did not have contraindications in 58% of the cases."
"The rate of virological responses at week 24 was high (74% for telaprevir and 60% for boceprevir), with a trend for a better virological response in genotype 1b and non-cirrhotic patients," they concluded.
Salmon added that these results must be viewed with caution until assessment of sustained virological response (SVR), as relapse can occur during the last months of therapy or after the end of treatment. (A cure is typically defined as continued undetectable HCV at 12 or 24 weeks post-treatment, known as SVR12 or SVR24).
Poizot Martin I et al (presented by D Salmon) Access to HCV triple therapy with telaprevir or boceprevir in real-life setting in HIV-HCV co-infected patients – ANRS CO13 HEPAVIH Cohort (France). 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Kuala Lumpur, abstract TUAB0102, July 2013.