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

GHIGLIONE, YANINA; POLO, MARÍA LAURA; SALOMON H; POBLETE, GABRIELA; PEREZ H; SALOMÓN, HORACIO; FLORENCIA QUIROGA; TURK, GABRIELA; LEWIN, SHARON R; LAUFER, NATALIA

Amsterdam

Congreso; 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 notcompletely understood. We hypothesized that cure of HCV would reduce persistent interferon (IFN) signaling and would have downstreameffects on the frequency of infected cells and their basal transcriptionalactivity.Methods: Nineteen HIV/HCV coinfected individuals on suppressiveART were treated for HCV with sofosbuvir/daclatasvir±ribavirine (12-24weeks). 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 ARTwere included as controls. Cell-associated HIV DNA (total, integrated,2LTR) and unspliced (US) and multiply spliced (MS) RNA were quantifiedby real-time PCR. Data was analyzed using non-parametric statistics.CD4 and CD8 cell frequency was determined by flow cytometry.Results: In the HIV/HCV coinfected group, 79% were male (meanage=49±5.9 years old). The mean times of HIV and HCV diagnosis were16.2±4.8 years and 13.5±7.3years, respectively. Median CD4+ T-cell countat enrollment was 291 cells/µL (IQR 231-776). All were under cART withundetectable HIV VL. Among the control group, 82% were male, withmedian CD4+ T-cell count=612 cells/µL (IQR476-863). US HIV RNA wassignificantly 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, Therewere no statistically significant differences in HIV MS RNA, 2LTRs or totaland integrated HIV DNA between EOT and BL or between HIV/HCV andHIV-only individuals. At EOT compared to BSL, HIV/HCV subjects hadsignificantly higher CD4/CD8 ratios (0.42 (IQR 0.29-0.71) versus 0.50 (IQR0.31-0.76), p=0.02). This was a result of an increase in CD4+ T-cells butminimal change in CD8+ T-cell counts.Conclusions: HCV/HIV individuals showed higher levels of HIV unspliced-RNA than HIV monoinfected individuals and this differencewas even greater after HCV clearance with DAAs. Thus, HCV clearance,or related downstream effects impact HIV persistence on ART. Thesechanges are consistent with reduced basal transcription in latently infected cells post-HCV clearance which could be secondary to reductionin chronic IFN signaling.