HCV-Specific CD4+ T-Cells Are Susceptible to HIV-1 and Contribute to Viral Persistence During Antiretroviral Therapy
Antiretroviral therapy (ART) reduces HIV-1 replication to undetectable levels but does not eliminate HIV-1 reservoirs, which persist in memory CD4+ T-cells of various antigenic specificities. Hepatitis C virus (HCV) coinfection is associated with an increase in HIV-DNA burden, but whether HCV-specific CD4+ T-cells are susceptible to HIV-1 infection and harbour replication-competent HIV reservoirs upon HCV resolution is unknown.
Methods
A cross-sectional study, published in eBioMedicine, examined the impact of HCV infection on CD4+ T-cell susceptibility to HIV-1 infection in vitro and reservoir persistence during ART in subjects with chronic HCV infection and uninfected controls (n = 20/group) and longitudinally in one ART-treated HCV+HIV+ individual who spontaneously resolved multiple episodes of HCV infection.
Findings
Memory CD4+ T-cells from subjects with chronic HCV exhibited superior permissiveness to productive HIV-1 infection in vitro (p = 0.03) compared to uninfected. This was proportional to plasma HCV-RNA levels (p = 0.046; r = 0.491). HCV-specific CD4+ T-cells distinguished from other antigenic specificities (e.g., Cytomegalovirus) by a CCR5+ (HIV-1 co-receptor), CXCR6+ (liver-homing marker) and CCR6+ (Th17 marker) phenotype and supported productive HIV-1 infection in vitro. In the HCV+ HIV+ subject, HCV-specific CD4+ T-cells carried replication-competent reservoir during acute HCV reinfection, with integrated HIV-DNA persisting in these cells upon HCV clearance.
Interpretation
The study provides evidence that HCV-specific CD4+ T-cells are targets of integrative HIV-1 infection and carry proviruses that persist during ART despite HCV resolution.