HIV-positive individuals coinfected with the easier-to-treat genotypes of hepatitis C virus may only require 24 weeks of hepatitis C therapy in order to achieve a sustained treatment response, according to an Irish study published in the May edition of HIV Medicine. The Irish doctors treated their patients with the same doses of anti-hepatitis C drugs used in individuals who only have hepatitis C, and provided supporting therapy, such as erythropoietin (EPO) to ensure that treatment was tolerable. A disappointing response to treatment was, however, seen in patients who were coinfected with harder-to-treat hepatitis C genotypes.
Significant numbers of HIV-positive patients are coinfected with hepatitis C virus. Since effective anti-HIV therapy became available, liver disease has emerged as one of the leading causes of illness and death amongst HIV-positive individuals in the United States and Europe. Standard treatment for hepatitis C virus coinfection in HIV-positive individuals is pegylated interferon with ribavirin. A sustained response to treatment (a negative hepatitis C viral load 24 weeks after the termination of therapy) has been seen in approximately 25 - 44% of HIV-positive patients who received anti-hepatitis C therapy, far lower than the response rate seen in individuals who only have hepatitis C.
Studies looking at the efficacy of hepatitis C therapy in HIV-positive patients have often used differing treatment schedules and doses and have frequently used lower doses of anti-hepatitis C drugs than those used in hepatitis C monoinfected patients because of concerns about safety.
Doctors at St James’s Hospital in Dublin wished to see how effective, safe and tolerable it was to use the doses of pegylated interferon, 1.5ug/kg/week and ribavirin 1000 – 1200mg/day that are used in patients who are only infected with hepatitis C virus in HIV/hepatitis C coinfected patients. As with standard hepatitis C therapy, patients who had the harder-to-treat hepatitis C genotypes 1 and 4 received 48 weeks or treatment, and patients with the easier-to-treat genotypes 2 and 3 received 24 weeks therapy. Response to treatment was checked at weeks four and twelve for all patients. Patients with genotypes 1 and 4 who did not have a response to therapy at week twelve were counted as failures and discontinued at this point. Individuals with genotypes 2 and 3 had treatment response monitored when they completed therapy at week 24 and they were checked 24 weeks later to see if their response to treatment had been sustained. Patients with genotypes 1 and 4 had treatment response evaluated at week 24, again on the completion of therapy at week 48 and then 24 weeks after the completion of treatment. Data were also gathered on physical side-effects, psychiatric adverse events and laboratory abnormalities.
A total of 45 patients were included in the study, which was open label, prospective and ran between the summer of 2001 and summer 2003. The majority of patients (27, 60%) were taking potent anti-HIV therapy and the median CD4 cell count was 436 cells/mm3 and median viral load was 50 copies/ml.
The harder-to-treat genotypes 1 and 4 were present in 17 patients with the remaining 28 individuals being infected with genotypes 2 or 3.
Overall, 28 patients (62%) had an end of treatment response and 24 individuals had a sustained virological response. However, when the investigators looked at these results further, they noticed that 75% of patients with genotypes 2 or 3 had a sustained virological response compared to just 19% of individuals with genotypes 1 and 4. In multivariate analysis, hepatitis C genotype was the only factor associated with the chances of achieving a sustained response to treatment (p = 0.005).
The investigators also established that all 15 patients who had a very early virological response to treatment – an undetectable hepatitis C viral load after four weeks– had a sustained virological response.
Side-effects were widely experienced, with 90% of patients reporting flu-like symptoms. In addition, ten patients (22%) experienced psychiatric problems and 18 (40%) individuals had haemotological toxicities. Eight patients stopped treatment early. This included two patients who died – one due to liver cancer and the other due to pneumonia.
Within the cohort, statistically significant falls in haemoglobin (14.7g/dl to 11.7g/dl, p
Erythropoietin (EPO) was prescribed to seven patients and two had blood transfusions. Intravenous EPO was prescribed to one patient.
No new illnesses related to HIV were observed and although there was a significant reduction in median CD4 cell count to 243 cells/mm3 (p
“This study demonstrates that, for HIV/HCV genotype 2 and 3 coinfected patients with a very early virological response, 24 weeks of full-dose hepatitis C virus therapy may be adequate to obtain a sustained virological response”, conclude the investigators.
They stress that the use of full-dose ribavirin, comparable to that used in patients who only have hepatitis C, and the use of growth factors and blood products in individuals experiencing haemotological side-effects were key to achieving these results.
Hopkins S et al. Role of individualization of hepatitis C virus (HCV) therapy duration in HIV/HCV-coinfected individuals. HIV Med 7: 248 – 254, 2006.