Reviewed by Susa Coffey, MD

Summary

Two recent studies, the large APRICOT trial (N = 868) and the smaller ACTG A5071 study (N = 133), have examined the efficacy of peginterferon alfa-2a (PEG) plus ribavirin (RBV) for the treatment of chronic hepatitis C (HCV) in patients coinfected with HIV. The studies differed somewhat in design and in patient characteristics, as well as in treatment (significantly, the initial dose of RBV was lower in the ACTG study). Both trials compared PEG plus RBV with standard interferon (IFN) plus RBV; APRICOT included a second control group treated with PEG plus placebo. The primary endpoint of sustained virologic response (undetectable HCV RNA 24 weeks after completion of 48 weeks of therapy) is shown below for the overall patient groups, and by genotype:

Significant findings of these studies include the following:

	Rates of sustained virologic response (SVR) were significantly higher in groups treated with PEG plus RBV than in control groups.
	Response rates in these HIV/HCV coinfection studies were lower than those seen in trials of similar treatment for HCV monoinfection (>40% SVR). (1, 2)
	Patients with genotype 1 (the majority of HCV patients in the United States) had a poor response to treatment, while those with genotypes 2 and 3 achieved SVR at high rates.
	For genotype 1 patients, SVR rates were higher in APRICOT than in ACTG A5071, due largely to a lower relapse rate in the APRICOT cohort after completion of therapy. The reasons for this are not clear, but may include the higher initial dose of RBV given in APRICOT.
	Subjects who did not have an early virologic response (at 12 weeks) did not achieve a sustained virologic response (the negative predictive value was 98-100%).
	In ACTG A5071, 35% of those with no early virologic response did demonstrate histologic improvement.
	During HCV treatment, CD4 counts declined by 100-150 cells/µL but CD4 percentages rose slightly; there were no differences in clinical progression of HIV disease among treatment groups.
	In APRICOT patients who had detectable HIV RNA at baseline, the HIV viral load decreased by 0.7 log10 copies/mL in the groups treated with PEG.
	Substantial numbers of subjects in both studies experienced treatment- or dose-limiting adverse effects.

Commentary

These studies make important contributions to our understanding of the treatment of HIV/HCV coinfected patients. However, issues remain to be addressed, including investigations into clinical outcomes following HCV treatment, specific patient characteristics that may be associated with improved treatment results, and the optimal stage in the course of HCV (or HIV) infection at which to initiate HCV treatment. In particular, further research is needed to develop therapies that are more effective, especially against genotype 1 HCV, and more tolerable to patients.

References

1.	Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.

2.	Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.

Related Articles

• Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, Peters MG, Koziel MJ, Bhan AK, Alston B, Colquhoun D, Nevin T, Harb G, van der Horst C; AIDS Clinical Trials Group A5071 Study Team. N Engl J Med 2004 Jul 29;351(5):451-9.