Long-term modification of the HIV reservoir after HCV clearance with direct-acting antivirals (DAAs): the potential role of Ribavirin.

MARÍA LAURA POLO; YANINA GHIGLIONE; JIMENA SALIDO; AJANTHA RHODES; ALICIA SISTO; HORACIO SALOMÓN; NATALIA LAUFER; GABRIELA TURK; ALEJANDRA URIOSTE; GABRIELA POBLETE; SHARON R. LEWIN

Mexico DF

Conferencia; 10th IAS Conference on HIV Science (IAS 2019); 2019

International AIDS Societty

Background: The effect of direct acting antivirals (DAAs) and ribavirin for hepatitis C virus (HCV) treatment on the persistence of HIV in HIV/HCV-coinfected individuals on antiretroviral therapy (ART) is not completely understood. Methods: In a prospective longitudinal observational study, HIV/HCV-coinfected individuals on suppressive cART (n=19) received sofosbuvir/daclatasvir alone (n=12) or with ribavirin (n=7). All achieved sustained virological response (SVR). Blood samples were obtained before HCV treatment (baseline sample, BSL), at end-of-treatment (EOT) and at 12 month after EOT (12MPT). Cell-associated (CA)-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. Results: Out of the enrolled subjects, 79% were male (mean age=49±5.9 years old). Median (IQR) time from HIV and HCV diagnosis were 16.3 (12-19.5) and 13.5 (9.5-17.5) years, respectively. Median (IQR) CD4+ T-cell count at enrollment was 291 (231-776) cells/μL. There were no statistically significant differences in CA-HIV DNA (total, integrated or 2LTR), for the three time points evaluated. Conversely, CA-US HIV RNA and the US/MS ratio were significantly higher in CD4+ T-cells collected at 12MPT compared to BSL (p=0.02 and p=0.03, respectively). In subjects not receiving ribavirin, statistically significant increments in CA US-RNA were observed at EOT and at 12MPT (both compared to BSL; p=0.0313 and p=0.0313, respectively). No such significant increments were observed in subjects who received ribavirin. Conclusions: Administration of DAAs alters the dynamics of HIV persistence in coinfected subjects with an increase in basal HIV transcription that persisted for 12 months after HCV clearance, particularly in those subjects not receiving ribavirin within their anti-HCV regimen. These differences between groups might provide insights into the mechanism controlling HIV expression.