1st International Workshop on HIV and Women, January 10-11, 2011, Washington, DC
Mark Mascolini
Canadian women coinfected with HIV and hepatitis C virus (HCV) did not differ from coinfected men in liver disease progression through 1 to 1.5 years of follow-up, though women and men did differ sociodemograpically and in risk behavior. The investigators noted that longer follow-up may be needed to identify potential gender-based progression differences in this cohort.
As people coinfected with HIV and a hepatitis virus live longer on antiretroviral therapy, liver disease progression poses a growing threat. Researchers established the Canadian Coinfection Cohort (CCC) to assess the impact of antiretroviral therapy and anti-HCV therapy on progression to end-stage liver disease. This analysis sought to determine whether gender affects progression of liver fibrosis in coinfected people.
The study involved coinfected people enrolled in the cohort from 2003 through 2009 at 16 centers across Canada. Study participants complete questionnaires on sociodemographics, drug use, and clinical care and give samples for biochemical, virologic, and immunologic studies every 6 months. CCC investigators determined the aspartate aminotransferase-to-platelet ratio index (APRI) as a fibrosis surrogate for all cohort members. An APRI at or above 1.5 has been validated as a marker of significant fibrosis and end-stage liver disease; that score corresponds to a biopsy score of F2 or higher. The investigators defined liver disease progression as reaching a score of 1.5 or higher during follow-up.
Of the 934 people enrolled, CCC researchers excluded 354 (38%) from this analysis because they already had an APRI of 1.5 or higher, already had end-stage liver disease, were transgendered, or had missing data. Of the remaining 580 cohort members, 422 (73%) were men and 158 (27%) women.
The study group had a median initial CD4 count of 396 (the same in women and men), 79% were taking antiretrovirals, and 54% had an HIV load below 50 copies. These measures, as well as distribution of HCV genotypes and initial APRI scores, were similar in women and men. However, women were younger (41 versus 45 years, P < 0.001) and more likely to be aboriginal (30% versus 10%, P < 0.001), to be heterosexual (87% versus 74%, P < 0.01), and to have a history of sex work (60% versus 40%, P < 0.001). A significantly lower proportion of women used alcohol (41% versus 52%, P < 0.05). A higher proportion of women than men had a history of injection drug use (88% versus 82%), but the difference was not statistically significant (P = 0.101).
Women had median HCV and HIV durations of 10.5 and 17.8 years, versus 11.8 and 18.8 in men. Median follow-up time was 1.0 years for women (interquartile range [IQR] 0.3 to 6.5) and 1.4 years (IQR 0.3 to 7.0) for men (P < 0.05). During follow-up the APRI score rose to 1.5 or higher in 71 people (12%) for an incidence of 9.7 per 100 person-years (95% confidence interval [CI] 7.4 to 11.9).
Among the 71 people whose APRI rose to 1.5 or higher, 23 were women and 48 were men. In an unadjusted analysis, liver disease progression by this measure appeared to be more frequent in women (11.5 per 100 person-years, 95% CI 8.0 to 19.1) than in men (8.5 per 100 person-years, 95% CI 6.1 to 10.9). But after statistical adjustment for age, duration of HIV and HCV, baseline APRI, HBV coinfection, active injection drug use, active alcohol use, nadir CD4 count, highest HIV viral load, prior treatment for HCV, and time-updated CD4 and HIV RNA, women did not have a significantly higher risk of progression (adjusted hazard ratio 1.53, 95% CI 0.90 to 2.67). Nineteen people died during follow-up, including 14 men and 5 women (difference not significant).
Two factors emerged as independent predictors of reaching an APRI at or above 1.5: An initial APRI below 0.5 more than quadrupled the risk (hazard ratio 4.6, 95% CI 2.5 to 8.4, P < 0.001). And every 100 cell higher time-updated CD4 count lowered the risk about 15% (hazard ratio 0.858, 95% CI 0.748 to 0.984, P < 0.05).
The CCO team concluded that sociodemographic and risk behavior patterns differ between HIV/HCV-coinfected women and men in Canada. But over the short term, there appeared to be no association between gender and liver disease progression. In HCV-monoinfected people, the investigators noted, liver disease has been reported to be milder in women than men. They stressed that the long gap between HCV infection and HIV infection--about 7 years in both women and men--point to a failure of HIV prevention in HCV-positive people. The link between higher CD4 count and slower liver disease progression indicates that improved immune function has liver-related benefits in coinfected women and men.
Reference
1. Pick N, Castillo E, Rollet K, et al. Gender and liver disease progression in HIV-hepatitis C co-infection. 1st International Workshop on HIV and Women. January 10-11, 2011. Washington, DC. Abstract O_21.
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