The effects of hepatitis C infection, treatment, and population interventions on all-cause mortality among people living with HIV Public Deposited

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  • March 22, 2019
Creator
  • Breskin, Alexander
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Approximately 25% of people living with HIV (PLWH) in the United States are co-infected with hepatitis C virus (HCV), which, if left untreated, causes mortality through decompensated cirrhosis and hepatocellular carcinoma. Direct-acting antiviral (DAA) treatment for HCV can produce sustained HCV virologic response in nearly all PLWH and HCV (PLWH+HCV). However, in the era of effective antiretroviral therapy (ART), the effects of HCV infection, treatment, and population interventions on mortality are not clear for PLWH. Using data from 3,056 PLWH in the Women’s Interagency HIV Study and Multicenter AIDS Cohort Study from 1994 to 2015, we used the parametric g-formula to estimate the effects of HCV infection and DAA treatment on 10-year all-cause mortality. We also estimated the effects of DAA treatment policies in which different groups are treated with DAAs: all PLWH+HCV, PLWH+HCV who met two existing Medicaid treatment criteria – achieving HIV suppression and having severe fibrosis or cirrhosis, and PLWH+HCV chosen at random with proportions treated equal to those under the Medicaid criteria. All estimates occurred after a hypothetical intervention to have all PLWH initiate ART at baseline, as modern guidelines suggest ART for all PLWH regardless of CD4 cell count. The estimated 10-year mortality risk difference (RD) for HCV infection was 4.3% (95% CI: 0.4%, 8.9%). The RD for DAA treatment was -3.7% (95%CI: -9.1%, 0.6%). The RD for treating those with HIV suppression and severe fibrosis or cirrhosis was -1.1% (95% CI: -2.8%, 0.6%). Under this policy, 51% (95% CI: 38%, 59%) of PLWH+HCV would be treated with DAAs. The RD for treating the same proportion of PLWH+HCV chosen at random was -1.9% (95% CI: -4.7%, 0.3%). The population attributable risk difference for treating all PLWH+HCV with direct acting antivirals (DAA) was -0.7% (95% CI: -1.8%, 0.1%). These results show that HCV is a major cause of mortality among PLWH, and that DAA treatment is effective at reducing mortality in this population. They also suggest that common DAA access criteria may be suboptimal and expanding access to these medications could lead to a substantial survival benefit among PLWH.
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Advisor
  • Adimora, Adaora
  • Westreich, Daniel
  • Cole, Stephen
  • Hudgens, Michael
  • Hurt, Christopher
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2018
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