Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

Abstract

Hepatitis C virus (HCV) co-infection and biological sex may each affect response to antiretroviral therapy (ART), yet no studies have examined HIV-associated outcomes by both HCV status and sex. We conducted a cohort study of HIV-infected adults initiating ART in Kaiser Permanente California during 1996-2011. We used piecewise linear regression to assess CD4 changes by sex and HCV status over 5 years. We used Cox regression to estimate hazard ratios (HR) by sex and HCV status for HIV RNA <500 copies/mL over 1 year, and for AIDS and death over the follow-up period. Among 12,865 subjects, there were 154 HIV/HCV-co-infected women, 1000 HIV/HCV-co-infected men, 1088 HIV-mono-infected women, and 10,623 HIV-mono-infected men. CD4 increases were slower in the first year for HIV/HCV-co-infected women (75 cells/μL) and men (70 cells/μL) compared with HIV-mono-infected women (145 cells/μL) and men (120 cells/μL; p<0.001). After 5 years, women had higher CD4 than men in both HIV-mono-infected (598 vs. 562 cells/μL, p=0.003) and HIV/HCV-co-infected individuals (567 vs. 509 cells/μL, p=0.003). Regardless of sex, HIV/HCV co-infection was associated with 40% higher mortality [95% confidence interval (CI): 1.2-1.6] compared with HIV mono-infection, but was not associated with AIDS (HR 1.1, 95% CI: 0.9-1.3) or achieving HIV RNA <500 copies/mL (HR 1.0, 95% CI: 0.9-1.1). HIV/HCV-co-infected men and women have slower CD4 recovery after starting ART and have increased mortality compared with HIV-mono-infected men and women. HCV should be aggressively treated in HIV/HCV-co-infected adults, regardless of sex.

FIG. 1.

Change in CD4 count over 5 years after ART initiation by sex and HCV status, Kaiser Permanente California, 1996–2011. ART, antiretroviral therapy; HCV, hepatitis C virus; HIV, human immunodeficiency virus. Mean CD4 counts were derived from a linear regression model including variables for HCV status, sex, time, and corresponding interaction terms. Generalized estimating equations accounted for within-individual correlation and piecewise linear curves allowed for a change in slope at 1 year. p Values test for differences in mean CD4 counts at baseline and 1, 3, and 5 years.

FIG. 2.

Virologic and clinical outcomes after ART initiation by sex and HCV status, Kaiser Permanente California, 1996–2011. ART, antiretroviral therapy; HCV, hepatitis C virus. Kaplan-Meier curves show the cumulative proportion without (a) attainment of HIV RNA <500 copies/mL within 1 year (n=8839), (b) clinical AIDS diagnosis (n=11,559), and (c) all-cause mortality (n=12,865) after ART initiation, by sex and HCV status. p Values are from log-rank tests.