HCV treatment with direct-acting antivirals (DAAs) in HIV/HCV coinfected subjects affects the dynamics of the HIV-1 reservoir

RHODES, A; PATTERSON P; QUIROGA, MF; LAUFER, N; Y. GHIGLIONE ; POBLETE; PEREZ, H; TURK, G; POLO, MARÍA LAURA; ROLÓN MJ; SALOMON, H; LEWIN, S

Amsterdam

Conferencia; The 22nd International AIDS Conference (AIDS 2018); 2018

Background: The effect of direct acting antiviral (DAA) agents for hepatitis C virus (HCV) on the HIV reservoir in co-infected individuals is not completely understood. We hypothesized that cure of HCV would reduce persistent interferon (IFN) signaling and would have downstream effects on the frequency of infected cells and their basal transcriptional activity.Methods: Nineteen HIV/HCV coinfected individuals on suppressive ART were treated for HCV with sofosbuvir/daclatasvir±ribavirine (12-24 weeks). Blood samples were obtained at enrollment, immediately before HCV treatment (baseline sample, BSL) and at end-of-treatment (EOT) for HCV. HIV-monoinfected individuals on at least one year of ART were included as controls. Cell-associated HIV DNA (total, integrated, 2LTR) and unspliced (US) and multiply spliced (MS) RNA were quantified by real-time PCR. Data was analyzed using non-parametric statistics. CD4 and CD8 cell frequency was determined by flow cytometryResults: In the HIV/HCV coinfected group, 79% were male (mean age=49±5.9 years old). The mean times of HIV and HCV diagnosis were 16.2±4.8 years and 13.5±7.3years, respectively. Median CD4+ T-cell count at enrollment was 291 cells/µL (IQR 231-776). All were under cART with undetectable HIV VL. Among the control group, 82% were male, with median CD4+ T-cell count=612 cells/µL (IQR476-863). US HIV RNA was significantly higher in CD4+ T-cells collected at EOT compared to BSL (p=0.01). HIV/HCV individuals had higher US HIV RNA at BSL (p=0.09) and EOT samples (p=0.005), compared to HIV-only individuals, There were no statistically significant differences in HIV MS RNA, 2LTRs or total and integrated HIV DNA between EOT and BL or between HIV/HCV and HIV-only individuals. At EOT compared to BSL, HIV/HCV subjects had significantly higher CD4/CD8 ratios (0.42 (IQR 0.29-0.71) versus 0.50 (IQR 0.31-0.76), p=0.02). This was a result of an increase in CD4+ T-cells but minimal change in CD8+ T-cell counts.Conclusions: HCV/HIV individuals showed higher levels of HIV unspliced-RNA than HIV monoinfected individuals and this difference was even greater after HCV clearance with DAAs. Thus, HCV clearance, or related downstream effects impact HIV persistence on ART. These changes are consistent with reduced basal transcription in latently infected cells post-HCV clearance which could be secondary to reduction in chronic IFN signaling.