HIV/HCV co-infected individuals who achieve a complete early response to interferon-based therapy for chronic hepatitis C have a 51% chance of achieving a sustained virological response using an extended 72-week course of treatment, researchers reported on Tuesday at the Sixteenth Conference on Retroviruses and Opportunistic Infections in Montreal, Canada.
Raymond Chung from Massachusetts General Hospital in Boston reported the latest results from the American SLAM-C (Sustained Long-term Antiviral Maintenance with Pegylated Interferon in HCV/HIV Co-infected Patients) trial, also known as ACTG A5178.
Co-infected individuals tend to respond less well to interferon-based therapy than people with hepatitis C virus (HCV) alone, and this study was designed to look at extended treatment and long-term pegylated interferon maintenance in non-responders.
SLAM-C consisted of three steps. First, 329 HIV/HCV co-infected patients were treated with 180 mcg/week pegylated interferon alfa plus weight-based ribavirin (1200mg/day for those weighing more than 75kg and 1000mg/day for those 75kg or less) for 12 weeks. At this point, participants were tested to see if they had achieved early virological response (EVR), that is, at least a two log10 decrease or undetectable (less than 600 IU/ml) HCV viral load.
In step 2, early responders continued to receive pegylated interferon plus ribavirin for a total duration of 72 weeks, while non-responders dropped ribavirin and continued on the same dose of pegylated interferon monotherapy. (The standard duration of hepatitis C treatment for co-infected people is 48 weeks regardless of HCV genotype.) Results from non-responders in step 2 were reported at last year's Retrovirus conference.
This year's report focused on step 3, looking at the 183 patients (56%) who achieved a partial or complete early virological response. Of these, 169 opted to continue on combination therapy through 72 weeks. Information about sustained virological response (SVR) - continued undetectable HCV viral load 24 weeks after the end of treatment - was available for 146 participants.
In the continuing group, most (89%) were men, the median age was 48 years, 52% were white, 29% were African-American, and 15% were Hispanic. This represented a shift from 43% white and 37% African-American in the original full study population, reflecting the fact that more blacks were non-responders.
Participants generally had well-controlled HIV disease, with 89% on antiretroviral therapy, 86% with HIV viral load below 50 copies/ml, and the median CD4 count was 316 cells/mm3 (lower than the median of nearly 500 cells/mm3 in the original population). Finally, just over three-quarters had hard-to-treat HCV genotypes 1 or 4, nearly one-third had prior interferon treatment experience, and 9% had cirrhosis.
About three-quarters of early responders were classified as having achieved complete EVR, defined as HCV viral load below 600 IU/ml, while the remainder were classified as having achieved partial EVR, with at least a two log10 drop, but 600 IU/ml or higher.
Overall, 51% of patients who achieved early virological response went on to achieve sustained virological response. The SVR rate was about twice as high amongst patients with HCV genotypes 2 or 3 compared with genotypes 1 or 4 (82% vs 42%, respectively). Participants with previous unsuccessful treatment attempts were half as likely to achieve sustained response as treatment-naive patients (30% vs 60%, respectively).
Furthermore, participants who had achieved complete EVR were nearly four times more likely to achieve sustained virological response than those with partial EVR (62% vs 17%, respectively).
As expected, the overall SVR rate was lower amongst African-Americans (38%) than amongst "non-black" patients (57%). This disparity was also seen in the partial responder group, but amongst patients who achieved complete EVR, the difference in SVR rates between blacks and whites was not statistically significant (54% vs 65%, respectively).
Many patients found extended duration therapy difficult to tolerate, and just over one-third (35%) stopped treatment before 72 weeks. The most common adverse events were known interferon or ribavirin side-effects such as muscle aches, depression, and blood-cell deficiencies. Fatigue and poor quality of life were the most frequently reported reasons for stopping therapy. A majority of early discontinuations and drug dose reductions due to side-effects occurred during the final 24 weeks of treatment.
Given the large disparity in sustained virological response rates between complete and partial early responders, Dr Chung noted that failure to achieve complete HCV clearance by week 12 identifies most patients who will not go on to achieve sustained response, thereby allowing likely non-responders to avoid further futile therapy.