Shorter Treatment Effective for HIV+ Men with Acute HCV

SUMMARY Acute hepatitis C treatment with pegylated interferon plus ribavirin was highly effective for HIV positive gay and bisexual men, even with a shorter 24-week duration of therapy.

By Liz Highleyman

Beginning around 2000 clinicians in large European cities began to report outbreaks of apparently sexually transmitted acute hepatitis C virus (HCV) among HIV positive men who have sex with men (MSM). Similar cases have since been seen in Australia and the U.S.

Studies of HCV monoinfected people have shown that treatment during the acute stage of infection is very effective, resulting in higher sustained virological response (SVR) rates than later treatment during chronic infection.

Acute HCV infection is often asymptomatic, however, and is usually not detected during this early period in HIV negative individuals. But HIV positive people taking antiretroviral therapy (ART) typically receive regular liver function monitoring, which can reveal liver enzyme elevations indicative of new HCV infection.

As described in the June 19, 2011, issue of AIDS, Femke Lambers and fellow investigators with the Dutch MOSAIC (MSM Observational Study of Acute Infection with Hepatitis C) study group evaluated the efficacy of treatment and the effect of duration of therapy in HIV positive men with acute hepatitis C.

For HCV monoinfected people, the standard duration of therapy for chronic hepatitis C is 24 weeks for those with genotypes 2 or 3, and 48 weeks for those with difficult-to-treat genotypes 1 or 4; 24 weeks is usually considered sufficient for acute infection regardless of genotype. For HIV positive people, however, many experts recommend the longer 48-week course for all genotypes, for both acute and chronic infection.

The present analysis included 50 HIV positive MSM at 2 hospitals in Amsterdam. All had acute HCV infection, defined as less than 2 years between the last negative HCV antibody or RNA test and the first positive test, and less than 2 years between the estimated time of infection (midpoint between the last negative and first positive test) and the start of treatment; 2 additional men met the inclusion criteria but spontaneously cleared HCV and were excluded from further analysis.

The participants' median age was 42 years. Most (68%) had HCV genotype 1, 26% had genotype 4, and just 6% had genotypes 2 or 3. About two-thirds were on antiretroviral therapy for HIV and the average CD4 cell count was high (about one-third each with < 380, 380-550, and > 550 cells/mm3).

All participants were treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus daily weight-adjusted ribavirin. The 21 patients (42%) at one hospital were to be treated for 24 weeks, while the 29 patients (58%) at the other were to be treated for 48 weeks. In actuality, not everyone was treated for the planned duration, with the shorter-duration group ranging from 22 to 36 weeks (median 24) and the longer-duration group ranging from 47 to 58 weeks (median 48).

Results

	3 patients (6%) stopped treatment around week 12 due to non-response.
	Another 3 (6%) stopped prematurely due to side effects.
	Among patients with available data at 4 weeks, 54% achieved rapid virological response (RVR).
	Among those with available data at 12 weeks, 87% achieved early virological response (EVR).
	44 patients (88%) had undetectable HCV RNA at the end of treatment.
	Overall, 38 people (76%) achieved SVR, or continued undetectable HCV RNA after completion of treatment.
	RVR and EVR were both highly predictive of SVR:
	Positive predictive values were 95% and 85%, respectively; Negative predictive values were 44% and 100%, respectively.
	The likelihood of SVR was higher with longer duration of therapy, but the difference did not reach statistical significance:
	In a univariate analysis, SVR was not significantly associated with treatment duration overall (odds ratio 1.53 for 48 vs 24 weeks). In a multivariate analysis adjusting for genotype and other factors, the effect of treatment duration was larger but still not significant (adjusted odds ratio 2.23). Among patients without RVR, 40% of those treated for 24 weeks and 64% treated for 48 weeks achieved SVR, but the numbers were small and the difference again did not reach statistical significance.

"The high SVR rate of 76% in this study confirms that treatment of HCV infection can be successful in HIV-infected patients when started in the acute phase and should encourage clinicians to treat this complicated patient group," the study authors concluded.

"Although the adjusted odds of attaining SVR was 2.2 times higher for 48 weeks of treatment compared with 24 weeks, this difference was not statistically significant," they continued. "This suggests that 24 weeks of treatment might be sufficient. This result strengthens the evidence for recommendations in current treatment guidelines for acute HCV infection in HIV coinfected patients. The shorter regimen would be of great advantage for patients, as both peginterferon and ribavirin can cause serious side effects."

Since this study was done, the advent of direct-acting antiviral agents has increased treatment response rates for people with chronic hepatitis C, when used in combination with pegyalted interferon/ribavirin. These new drugs have not yet been extensively studied for acute infection, but could potentially lead to higher response rates than current standard therapy alone.

Investigator affiliations: Department of Research, Public Health Service of Amsterdam, Cluster of Infectious Diseases, Netherlands; Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands; Section of Clinical Virology, Department of Medical Microbiology, Academic Medical Center, Amsterdam, Netherlands; Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands; National Institute of Public Health and the Environment, Bilthoven, Netherlands; Division of Infectious Diseases, Tropical Medicine and AIDS (CINIMA), Department of Internal Medicine, Academic Medical Center, Amsterdam, Netherlands.

6/17/11

Reference
FA Lambers, K Brinkman, J Schinkel, et al. for MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study group. Treatment of acute hepatitis C virus infection in HIV-infected MSM: the effect of treatment duration. AIDS 25(10):1333-1336 (abstract). June 19, 2011.