Early emergence of opportunistic infections after starting direct‐acting antiviral drugs in HIV/HCV‐coinfected patients

Abstract

Varicella-zoster virus and hepatitis B virus reactivations have been reported after starting interferon-free direct-acting antiviral agent (DAA) combinations. HIV/HCV-coinfected patients could be a high-risk group for the reactivation of latent infections. Because of these, we report the occurrence of severe infections after starting DAA regimens in HIV/HCV-coinfected patients. Individuals included in the HEPAVIR-DAA (NCT02057003) cohort were selected if they had received all-oral DAA combinations. A retrospective review of clinical events registered between the start of DAAs and 12 months after SVR12 was carried out. Overall, 38 (4.5%) of 848 patients presented infections. The incidence (95% confidence interval) of infections was 4.6 (3.3-6.3) cases per 100 person-years. The median (Q1-Q3) time to the infection since baseline was 23 (7.3-33) weeks. Five (13%) of the patients with infections died; four of them had cirrhosis. The frequency of previous AIDS was 21 (54%) for patients with infections and 324 (40%) for those without infections (P = 0.084). The median (Q1-Q3) nadir CD4 cell count of individuals with and without infections was 75 (53-178) and 144 (67-255) cells/μL, respectively (P = 0.047). Immunodepression-associated infections were observed in 9 (1.1%) patients. All of them had suppressed HIV replication with antiretroviral therapy. In conclusion, severe infections are relatively common among HIV/HCV-coinfected patients receiving all-oral DAA combinations. Some unusual reactivations of latent infections in patients with suppressed HIV replication seem to be temporally linked with DAA use.

Treg cells in the course of chronic hepatitis C virus infection partially normalize in longitudinal observation after successful DAA treatment regardless of hepatic fibrosis stage

“…Furthermore, there are reports of HBV and varicella-zoster reactivations following the start of DAA therapy [ 33 , 34 ]. There is also a description of increased incidence of opportunistic infections in HIV/HCV coinfected patients appearing around 23 weeks after the beginning of DAA therapy [ 35 ]. We cannot exclude that those observations may be related to the persistence of an increased number of circulating Treg cells after DAA therapy.…”

A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection

“…In summary, studies examining DAA-mediated cure of HCV, mostly in monoinfected subjects, suggest only partial reconstitution of immune functions and persistence of immune suppressive cells like Tregs and MDSC. This immune suppressive environment may contribute to reduced immune response to vaccinations, limited immune surveillance against cancer, and increased reactivation of latent or occult infections of herpesviruses and hepatitis B virus, respectively ( 240 , 241 ). Finally, this incomplete reconstitution of HCV-specific CD4 + and CD8 + T cells may increase the risk of HCV persistence upon re-exposure and reinfection in high-risk populations like PWID and MSM.…”

Long term immunological perturbations post DAA therapy in chronic HCV/HIV co-infected patients

“…In summary, studies that describe DAA-mediated clearance of HCV, suggested only limited recovery of the immune system and an immune suppressive environment with persistence of cells like Tregs and MDSC. These immune suppressive conditions might decrease immune response to vaccinations, reduce immune surveillance against cancer, and increase re-activation of latent infections of herpesviruses and hepatitis B virus, respectively (Macias et al, 2019a;Fabbri et al, 2017). Finally, an incomplete reconstitution of HCV-specific CD4+ and CD8+ T cells might increase the risk of HCV persistence upon reexposure and re-infection in high-risk populations like HCV/HIV co-infected patients.…”