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Risk of Progression to Fibrosis Twice Higher in Women Than Men With HCV/HIV
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Third International Workshop on HIV and Women, January 14-15, 2013, Toronto
Mark Mascolini
Canadian women coinfected with HIV and hepatitis C virus (HCV) ran twice the risk of progression to liver fibrosis as men, according to results of a 300-person multicenter prospective study. Demographics, HCV duration, alcohol use, and other differences between women and men did not explain the difference in progression to fibrosis.
HIV-negative men with HCV infection have faster progression to liver fibrosis than women. But progression had not been explored in HCV/HIV-coinfected people until researchers began tracking this cohort of 1119 coinfected Canadians, 26% of them women. Participants made study visits every 6 months during the period 2003-2012.
The researchers used an AST-to-platelet ratio index (APRI) of 1.5 or greater to indicate significant fibrosis. That APRI corresponds to a biopsy score of F2 or greater. The investigators limited the analysis to 308 HCV PCR-positive antiretroviral-treated people with at least two visits, with an APRI below 1.5 at the initial visit, and without current anti-HCV treatment or a history of end-stage liver disease.
The study used a multivariate model adjusted for baseline age, alcohol use, cigarette smoking, HCV duration, CD4 count, APRI, and time-updated HIV viral load to assess the effect of gender on risk of developing an APRI score of 1.5 or greater.
Of the 308 participants, 87 (28%) were women. Age averaged 44.9 years overall, and women were significantly younger (average 42.0 versus 44.1, P = 0.003). Most study participants reported a history of injection drug use, and 81 were active injectors (43% of women and 38% of men, not significant). Women were more likely to be aboriginal than men (25% versus 16%, P = 0.005) but were less likely to abuse alcohol (14% versus 31%, P = 0.023). A higher proportion of women than men engaged in sex work or patronized sex workers (54% versus 44%, P = 0.027).
Median durations of HIV and HCV infection did not differ significantly between women and men (11.4 and 19.1 years overall). Median time since antiretroviral therapy began stood at 5.7 years, and about two thirds of women and men (64% and 67%) took a protease inhibitor-based combination. Median baseline CD4 count measured 373, 73% of study participants had an undetectable viral load, and these values were similar in women and men.
Total follow-up time at risk measured 544 person-years, 129 person-years among women and 415 person-years among men. APRI scores rose to 1.5 or greater in 55 people (18%), including 18 women (21%, 14.0 per 100 person-years, 95% confidence interval [CI] 7.5 to 20.4) and 37 men (17%, 8.9 per 100 person-years, 95% CI 6.0 to 11.8).
Multivariate analysis determined that being a woman more than doubled the risk of liver fibrosis progression (adjusted hazard ratio [aHR] 2.26, 95% CI 1.24 to 4.11, P = 0.008). Every 10-fold higher time-updated HIV load raised the risk 35% (aHR 1.35, 95% CI 1.00 to 1.83, P = 0.05), and baseline APRI more than quintupled the risk (aHR 5.49, 95% CI 2.75 to 10.97, P = < 0.001). Factors that did not affect progression to fibrosis in this analysis were age, HCV duration, alcohol use at baseline, or cigarette smoking at baseline.
In other statistical models, aboriginal ethnicity, injection drug use history, and time-updated CD4 count were not associated with fibrosis progression. Including those factors in the primary analysis did not alter the results.
The researchers concluded that women had a significantly greater risk of progression to fibrosis than men, when fibrosis is calculated by APRI. The higher risk in women, the researchers stressed, "was not explained by obvious differences between men and women in sociodemographics, duration of HCV infection, alcohol exposure, or virologic and immunologic responses to antiretroviral therapy as the rates of liver fibrosis remained elevated after adjusting for these factors."
The investigators suggested that "metabolic factors or antiretroviral therapy-induced liver toxicity may differ between men and women and play roles in accelerating liver fibrosis in women." Also, a recent study of the same cohort found that antiretroviral interruption was associated with fibrosis progression more often in women than men [2].
References
1. Rollet KC, Moodie EEM, Pick N, et al. Female gender is associated with liver fibrosis progression in antiretroviral treated HIV-HCV co-infected patients. Third International Workshop on HIV and Women, January 14-15, 2013, Toronto. Abstract O_09.
2. Thorpe J, Saeed S, Moodie EE, Klein MB; Canadian Co-infection Cohort Study (CTN222). Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-hepatitis C virus co-infection. AIDS. 2011;25:967-975.
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