SUMMARY: HIV positive gay/bisexual men with acute hepatitis C virus (HCV) coinfection responded as well to 24 weeks of interferon-based therapy as they did to 48 weeks, even though most had hard-to-treat HCV genotypes 1 or 4, researchers reported in a poster presented this week at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) in San Francisco.

By Liz Highleyman

Over the past decade, researchers have been reporting outbreaks of acute HCV infection among HIV positive men who have sex with men (MSM), first in large cities in the U.K. and Europe, and later in Australia and the U.S. The natural history of liver disease progression and response to treatment in individuals who already have HIV when they acquire HCV is not fully understood.

Femke Lambers and colleagues conducted a retrospective analysis to evaluate the efficacy of treatment of acute HCV infection and the effect of treatment length on outcomes among HIV positive MSM in Amsterdam.

The researchers looked at all HIV/HCV coinfected MSM from 2 HIV outpatient clinics in the city. Date of HCV infection was assumed to be the midpoint between the last HCV negative test (either HCV antibody or HCV RNA) and the first positive test.

For this analysis, they selected 52 individuals with an interval of less than 2 years between both tests, and less than 2 years between estimated date of infection and treatment initiation.

The median age was 41 years and the median time from estimated HCV infection to treatment was 244 days (IQ range 118 to 353). At the time of hepatitis C diagnosis, the median CD4 count was about 450 cell/mm3 and almost all had elevated ALT levels.

A majority (30 men) had HCV genotype 1, the hardest type to treat; 1 person each had genotypes 2 and 3. The second most prevalent genotype was 4 (also considered hard-to-treat), present in 10 men (genotype 4 is uncommon in Europe overall, but seen often in the MSM outbreaks). Finally, 4 men had an unknown genotype.

Standard therapy for chronic hepatitis C is pegylated interferon (Pegasys or PegIntron) plus weight adjusted ribavirin lasting 24 weeks for patients with genotypes 2 or 3, and 48 weeks for those with genotypes 1 or 4. Studies have suggested that shorter therapy, and possibly pegylated interferon monotherapy, can be highly effective if started during the acute phase of infection.

Results

	2 participants experienced spontaneous HCV clearance without treatment.
	20 patients started therapy with the intention of treating for 24 weeks, while 26 intended to treat for 48 weeks.
	44 participants completed treatment.
	6 patients prematurely discontinued treatment due to side effects or lack of response at week 12.
	34 men experienced sustained virological response (SVR), or continued undetectable HCV RNA 6 months post-treatment (4 had not yet finished post-treatment follow-up).
	In an intention-to-treat-analysis, the overall SVR rate was 74% (34 out of 46).
	Broken down by genotype, 70% of genotype 1 patients and 90% with genotype 4 achieved SVR (1 of 2 with genotypes 2 or 3 did so as well -- an unusually low response rate of 50% -- but the numbers were too small to be meaningful).
	Overall, neither time between infection and treatment initiation nor length of treatment was significantly associated with treatment outcomes.
	70% of patients treated for 24 weeks achieved SVR compared with 77% of those treated for 48 weeks, not a significant difference.
	90% of patients who experienced rapid virological response at week 4 achieved SVR, compared with only 50% of those without SVR.

Based on these findings, the researchers concluded, "A high SVR rate of 74% was reached in this group of HIV-infected MSM with acute HCV infection." This compares to a rate of about 50% for people with genotype 1 chronic hepatitis C.

"No significantly difference in treatment outcome was observed between 24 and 48 weeks treatment length," they continued, adding that, "24 weeks of peg-interferon and ribavirin might be sufficient for treatment of acute HCV infection in HIV-infected patients."

Public Health Service, Amsterdam, Netherlands; Onze Lieve Vrouwe Gasthius, Amsterdam, Netherlands; Academic Medical Center, Amsterdam, Netherlands; National Institute of Public Health and the Environment, Bilthoven, Netherlands.

2/19/10

Reference
F Lambers, G van den Berk, J van der Meer, and others. Treatment Outcome of Acute Hepatitis C Virus Infection in HIV-infected MSM: The Effect of Treatment Length. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 641.