Coinfection

Can Rapid Virological Response Predict Sustained Response to Pegylated interferon plus Ribavirin in HIV-HCV Coinfected Patients?

Research has shown that HIV positive people with hepatitis C virus (HCV) coinfection tend to respond less well to interferon-based therapy, but the factors that predict favorable response are generally similar. The objective of the current study, published in the August 2008 issue of the Journal of Viral Hepatitis, was to evaluate the role of rapid virological response in predicting sustained virological response to anti-HCV therapy.

The study included 65 HIV-HCV coinfected participants who received combination treatment with pegylated interferon plus ribavirin for 24 to 48 weeks, depending on HCV genotype. A majority of the patients were men. More than half (55%) were on HAART and the mean CD4 count was 502 cells/mm3.

Rapid virological response (RVR) was assessed at week 4 (RVR), early virological response (EVR) at week 12, end-of-treatment response (ETR) at week 24 or 48, and sustained virological response (SVR) 24 weeks after completion of therapy. The primary end-point was undetectable HCV RNA at 24 weeks after treatment completion.


Results

Based of these findings, the study authors concluded, "Achievement of RVR, a negative HCV PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups."

"More significantly," they noted, "[these] data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients coinfected with genotype 2/3 disease for whom 6 months [of] full dose therapy may be sufficient to obtain a SVR."

Discussion

As has been noted by other researchers, utilizing HCV viral kinetics may play a pivotal role in successfully treating patients. In HCV monoinfected individuals, the use of virological response at week 12 (EVR) has long been accepted as a juncture point at which a decision to continue or discontinue treatment can be made. Numerous researchers have concluded that treatment of HCV monoinfected patients can be confidently discontinued at week 12 if EVR is not achieved, which has benefits in terms of reduced cost and side effects.

However, according to the authors, "Such an early discontinuation rule could not be automatically adopted when treating HCV-HIV coinfected patients. Moreover, the perceived slower virological response and the increased relapse rates observed in original studies of coinfected patients suggested the need for a longer duration of HCV therapy for HIV-HCV patients."

"In our study," wrote the authors, "failure to achieve EVR had 100% negative predictive value for SVR. This is in keeping with similar findings by the RIBAVIC and APRICOT study groups when analyzing week 12 viral response."

Historically, international guidelines have recommended 48 weeks of anti-HCV therapy for all coinfected patients, regardless of genotype. "Our findings lend further support to the recently updated consensus guidelines, which now recommend shortening duration of treatment in a sub-group of those coinfected with genotype 2/3 disease," wrote the authors.

Finally they observed, "Clearly, use of RVR in the setting of maintenance of full dose HCV therapy will identify a cohort for whom 24 weeks' treatment will successfully achieve [the] primary outcome. This finding further strengthens this groups' previously published recommendation on the need to individualize duration of HCV therapy for HIV-HCV coinfected patients."

Department of Genitourinary and Infectious Diseases, St James's Hospital, Dublin, Ireland; UCD School of Medicine and Medical Sciences, Dublin, Ireland; Department of Hepatology, St James's Hospital, Dublin, Ireland.

7/18/08

Reference 

DO Shea, H Tuite, G Farrell, and others. Role of rapid virological response in prediction of sustained virological response to Peg-IFN plus ribavirin in HCV/HIV co-infected individuals. Journal of Viral Hepatitis 15(7): 482-489. July 2008.