SUMMARY: Rapid virological response (RVR), or undetectable HCV viral load at 4 weeks, was confirmed to be a strong predictor of sustained response among HIV/HCV coinfected patients, as it is in people with hepatitis C alone, according to findings presented at the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) in Boston. However, a substantial proportion of people who did not show rapid response still went on to achieve sustained response, emphasizing the importance of not stopping treatment too soon in this population.

By Liz Highleyman

Standard therapy for genotype 1 chronic hepatitis C virus (HCV) infection -- for both HCV monoinfected and HIV/HCV coinfected patients -- consists of pegylated interferon plus ribavirin for 48 weeks.

Interferon-based therapy can cause difficult side effects, however, and only about half of people with this hard-to-treat genotype achieve a cure. People who do not show evidence of response during earlier stages of treatment, therefore, are typically advised to stop therapy ahead of schedule, since they are unlikely to go on to achieve sustained response.

Prior research has shown that both HCV monoinfected and HIV/HCV confected patients with rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of therapy, are highly likely to achieve sustained virological response (SVR), or continued undetectable HCV viral load 24 weeks after completion of therapy. Some studies suggest HIV/HCV coinfected individuals may respond more slowly, however, so stopping rules for monoinfected patients might lead to premature discontinuation for coinfected patients who could benefit from longer treatment.

Mark Sulkowski from Johns Hopkins University School of Medicine and fellow investigators with the PARADIGM study looked at 410 HIV/HCV coinfected patients with HCV genotype 1; 388 with complete data were included in the analysis.

Most participants (81%) were men, the mean age was 45 years, 34% were black, and 27% were Hispanic. Participants had generally well-controlled HIV disease; 74% had undetectable viral load and the mean CD4 cell count was about 500 cells/mm3. The average baseline HCV RNA level was 6.46 log IU/mL and 11% had liver cirrhosis.

Participants were randomly assigned to 48 weeks of treatment with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus ribavirin at either a fixed dose of 800 mg/day or a weight-adjusted dose of 1000-1200 mg/day.

In this analysis, patients were grouped according to RVR status at week 4; those without RVR (defined as HCV RNA still >20 IU/mL) were further subdivided according to the magnitude of HCV RNA reduction at week 4 (>3 log; 2-3 log; 1-2 log; < 1 log).

The researchers then determined the proportion of patients in each category with complete early virological response (cEVR) -- or undetectable HCV RNA (< 20 IU/mL) at week 12 -- and SVR at week 72 (48 weeks of treatment plus 24 weeks of follow-up).

Results

	RVR, cEVR, and SVR rates were similar for both ribavirin dose regimens, so these data were combined.
	As expected, there was a large difference in SVR rate between patients with and without RVR: 71% vs 17%, respectively.
	Among non-RVR patients, the probability of cEVR rose according to the magnitude of HCV RNA decrease at week 4:
	>3 log drop: 91%; >2 log: 45%; >1 log drop: 14%; < 1 log drop: 1%.
	A similar pattern was seen for SVR:
	>3 log drop: 56%; >2 log: 40%; >1 log drop: 13%; < 1 log drop: 3%.
	Among the patients who did not have RVR but did have cEVR, 64% went on to achieve SVR.

"RVR is a strong predictor of achieving a SVR," the researchers concluded. "However, among non-RVR patients, those that achieved at least a 2-log decrease in HCV RNA by week 4 of treatment had good rates of SVR when treated with [pegylated interferon alfa-2a] plus ribavirin."

"Non-RVR patients achieving a cEVR had high rates of SVR," they continued. "A decrease in HCV RNA of more than 2-log by week 4 or clearance of HCV RNA by week 12 should be considered a strong incentive to complete the planned treatment duration in [HIV/HCV] coinfected genotype 1 patients."

Investigator affiliations: Johns Hopkins University School of Medicine, Baltimore, MD; St. Michael's Medical Center, Newark, NJ; Virginia Commonwealth University, Richmond, VA; University of California San Diego, San Diego, CA; Hospital del Mar, Barcelona, Spain; Hospital Sao Joao, Porto, Portugal; The Research Institute, Springfield, MA; Roche, Nutley, NJ, United States; Fundacion de Investigacion De Diego, Santurce, Puerto Rico.

11/23/10

Reference
MS Sulkowski, J Slim, RK Sterling, and others. Sustained virologic response (SVR) rates in HIV-HCV G1 co-infected patients according to the magnitude of HCV RNA decrease at week 4 of treatment with peginterferon (PegIFN) alfa-2a (40KD) plus ribavirin (RBV) in the PARADIGM study. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 920.