August 14, 2015
Adults coinfected with hepatitis C (HCV) and HIV gained CD4+ cells more slowly after starting antiretroviral therapy than people infected only with HIV, according to results of a large cohort study in California. Coinfected patients also had greater all-cause mortality over the study period.
HCV coinfection is highly prevalent in certain HIV populations because the viruses share transmission routes. Research indicates that both HCV and biological sex may affect response to antiretroviral therapy, but no work has addressed treatment outcomes by both HCV status and sex. To address that research gap, investigators from Kaiser Permanente California analyzed response to antiretroviral therapy and progression to AIDS or death in HIV-positive men and women with or without HCV coinfection.
The analysis involved HIV-positive adults who started antiretroviral therapy in the Kaiser Permanente health care system at some point from 1996 through 2011 and had their CD4+ cell count and viral load measured within six months before starting treatment. Researchers recorded four outcomes: CD4+ cell count in the first five years of treatment; attainment of viral load below 500 copies/mL in the first year of treatment; clinical AIDS diagnosis through 2011; and death through 2010.
In the first year of antiretroviral therapy, CD4+ cell count rose more slowly in HIV/HCV coinfected women (75 cells/mm3) and men (70 cells/mm3) than in HIV-monoinfected women (145 cells/mm3) and men (120 cells/mm3). After the first year of antiretroviral therapy, CD4+ cell gains were greatest in HIV-monoinfected women (30 cells/mm3 per year), followed by HIV/HCV-coinfected women (27 cells/mm3 per year), HIV/HCV-coinfected men (23 cells/mm3 per year) and HIV-monoinfected men (22 cells/mm3 per year). After five years of antiretroviral therapy, women had significantly higher CD4+ cell counts than men whether HIV-monoinfected (598 versus 562 cells/mm3, P = .003) or HIV/HCV-coinfected (567 versus 509 cells/mm3, P = .003).
Cox regression analysis found no link between HIV/HCV coinfection and reaching an HIV load below 500 copies/mL or risk of AIDS through 2011. But Cox regression tied coinfection to a 40% higher risk of death (adjusted hazard ratio [aHR] 1.4, 95% confidence interval [CI] 1.2 to 1.6), regardless of sex. Liver-related death largely drove the association between coinfection and all-cause mortality (aHR 6.0, 95% CI 3.9 to 9.0), but coinfected people did not have a higher AIDS death risk.
The association between HIV/HCV coinfection and diminished CD4+ response in the first year of antiretroviral therapy, but not later, reflects results of a recent meta-analysis. The Kaiser Permanente researchers proposed that differences in behavioral factors (such as substance use), biological factors (such as pharmacokinetics) or sex hormones could explain the better CD4+-cell response in women than men regardless of HCV status. Women may also have higher CD4+ cell counts than men regardless of HIV status.
Because HIV/HCV coinfection may raise the risk of all-cause mortality, the authors suggested, "HCV infection should be aggressively treated among HIV-infected individuals as recommended, regardless of sex."
Mark Mascolini is a freelance writer focused on HIV infection.
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