HIV/HCV Coinfected Women More Likely than Men to Modify or Discontinue Hepatitis C Treatment

		SUMMARY: HIV positive women with chronic hepatitis C virus (HCV) coinfection experienced side effects of interferon-based therapy that were similar to those of coinfected men, but women developed these side effects sooner and were more likely to discontinue anti-HCV therapy or lower their doses for this reason, according to a study described in the October 1, 2010 Journal of Acquired Immune Deficiency Syndromes. Researchers also found that use of specific antiretroviral drugs can help predict adverse events during hepatitis C treatment.

By Liz Highleyman

People with HIV/HCV coinfection tend to experience more rapid liver disease progression and respond less well to interferon-based hepatitis C treatment compared to patients with HCV alone.

Some research also suggests that coinfected individuals may experience worse side effects, due to drug interactions or other reasons. In various studies adverse events accounted for approximately 10% to 40% of hepatitis C treatment discontinuations. But the influence of sex on these side effects has not been extensively studied.

Debika Bhattacharya from the University of California at Los Angeles and colleagues performed a meta-analysis of prior clinical trials to assess the effects of sex and other predictors of adverse events during hepatitis C treatment in coinfected patients.

The meta-analysis included data from 3 key randomized trials of conventional or pegylated interferon (Pegasys or PegIntron), with or without ribavirin: APRICOT, ACTG 5071, and ANRSHCO2-RIBAVIC. The primary endpoints assessed were adverse events requiring treatment discontinuation or interferon or ribavirin dose modification.

Together, the analysis included 1376 study participants, 21% of whom were women. Nearly two-thirds (61%) were on antiretroviral therapy (ART) and had undetectable HIV viral load, while 14% were antiretroviral treatment-naive. The combined median CD4 cell count was 485 cells/mm3.

Results

	17% of participants in the 3 trials discontinued hepatitis C treatment due to adverse events.
	50% of patients modified their interferon or ribavirin doses due to adverse events.
	Women in these studies experienced more adverse events requiring treatment discontinuation compared with men (24% vs 16%; P = 0.003).
	Women also experienced more adverse events leading to dose modification (61% vs 48%, respectively; P < 0.0001).
	Types of adverse events leading to treatment discontinuation or dose modification were similar in women and men.
	However, these types of adverse events occurred earlier in women.
	74% of adverse events requiring treatment discontinuation and 49% of events leading to dose modification involved constitutional symptoms.
	Depression accounted for 18% of adverse events requiring treatment discontinuation.
	Neutropenia (low white blood cell count) accounted for 26% of adverse events leading to dose modification.
	Looking at events requiring treatment discontinuation, there were significant interactions between sex and body mass index (BMI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) use:
	More adverse events among men with lower BMI; More events among women taking NNRTIs.
	The following factors were significantly associated with adverse events leading to dose modification:
	Use of pegylated interferon: odds ratio (OR) 2.07, or about double the risk; Older age: OR 1.48 per 10 years; Advanced liver fibrosis or cirrhosis (Ishak score F5-F6): OR 1.42; HCV genotypes 1 or 4: OR 1.31; Lower hemoglobin level (an indicator of anemia): OR 1.23 per g/dL; Lower BMI: OR 1.04 per kg/m; Lower absolute neutrophil count (an indicator of neutropenia): OR 1.04 per 500 cells/mm.
	For adverse events requiring dose modification, there were significant interactions between sex and being antiretroviral-naive and use of zidovudine (AZT; Retrovir):
	More events among antiretroviral-naive women; More events among antiretroviral-experienced men; More events among women who took zidovudine, which can cause anemia.

Based on these findings, the study authors concluded, "Although there was no difference in type of adverse events, adverse events requiring treatment discontinuation and adverse events requiring first dose modification were more frequent and occurred earlier in women."

"In women, antiretroviral regimen may be an important predictor of adverse events requiring treatment discontinuation during HCV therapy and should be explored as a predictor of adverse events in HIV/HCV coinfection trials," they recommended.

Investigator affiliations: University of California, Los Angeles, CA; Harvard School of Public Health, Boston, MA; UMR-S 707, UPMC-Paris 6 and INSERM, Paris, France; Saint-Antoine Hospital, APHP, Paris, France; Massachusetts General Hospital, Harvard University School of Medicine, Boston, MA; University of California, San Francisco, CA; University of California, San Diego, CA.

10/22/10

Reference
D Bhattacharya, T Umbleja, F Carrat, and others. Women experience higher rates of adverse events during hepatitis C virus therapy in HIV infection: a meta-analysis. Journal of Acquired Immune Deficiency Syndromes 55(2): 170-175 (Abstract). October 1, 2010.