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.

Narrowing the Gap in Life Expectancy Between HIV-Infected and HIV-Uninfected Individuals With Access to Care

“…Hepatitis C virus (HCV) status was determined by HCV-antibody tests or HCV RNA levels, or, for KPNC, by inclusion in the KPNC viral hepatitis registry, as previously described. 22 …”

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…Numerous studies have found that hepatitis B virus (HBV), hepatitis C virus (HCV), and CMV coinfections were associated with poor CD4 + T‐cell immune recovery in HIV‐1‐infected individuals on ART. The precise mechanism by which HBV, HCV, and CMV coinfections may have deleterious effects on CD4 + T‐cell count recovery is unclear.…”

Modelling CD4 T Cell Recovery in Hepatitis C and HIV Co-infected Children Receiving Antiretroviral Therapy

“…In a recent paper by Marcus et al, 39 it was shown that HIV/HCV coinfected adults have delayed CD4 + T cell reconstitution on ART, relative to their monoinfected counterparts. Similarly, a meta-analysis conducted by Tsiara et al 40 in 2013 of 21 studies involving 22,533 adult patients reported that even though HCV had a demonstrable adverse effect on immune reconstitution in the first 2 years of ART, this trend was not sustained in the long term.…”