Longitudinal evaluation of viral interactions in treated HIV-hepatitis B co-infected patients with additional hepatitis C and D virus

Abstract

Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV-HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV-HCV (39.7, 4.1); 12 HBV-HDV (35.2, 9.9); 12 HBV-HCV-HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95%CI 1.13-13.10, P = 0.03) and HCV tri-infection (aOR = 2.65, 95%CI 1.03-6.81, P = 0.04), but marginally associated with HIV-HBV-HCV-HDV (aOR = 2.32, 95%CI 0.94-5.74, P = 0.07). In quad-infection, lower HDV-undetectability (vs HIV-HBV-HDV, P = 0.2) and higher HCV-undetectability (vs HIV-HBV-HCV, P = 0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up (vs HIV-HBV co-infection): HIV-HBV-HCV = 2.23-5.67, HIV-HBV-HDV = 1.53-15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.

Hepatitis delta-associated mortality in HIV/HBV-coinfected patients

“…The prevalence of HDV infection in our cohort was similar to the findings from the EuroSIDA collaboration but slightly higher than the estimate reported in cohort studies from France and North America 17,18 . As false-positive HDV screening results seem to be frequent in the setting of HIV-infection 19 , we performed a confirmatory serology in all patients with a negative HDV RNA in order to strengthen our HDV prevalence estimate.…”

“…Injection drug use being the most probable route of HDV transmission for the majority of patients included in our study, HCV infection was also present in many of them. The complex interplay between HBV, HCV and HDV has been described in several previous reports which generally showed HDV to be the dominant virus, often leading to the suppression of HBV as well as HCV 17,22,23 . In line with these findings, only 20% of HIV/HBV/HDV-coinfected patients and 10% of HIV/HBV/HDV-coinfected patients with replicating HDV in our cohort had a replicating HCV infection compared to 60% of HDV-negative individuals.…”

Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda

“…This data may suggest that ART may not affect HDV antibodies however a larger study is required to assess the impact of ART on HDV infection 8 . However, HIV may increase the risk of HDV acquisition since immunosuppressive states increase the likelihood of chronic hepatitis B which serves as a buffer to hepatitis D acquisition.…”

“…Triple infection with HDV/ HBV and human immune deficiency virus (HIV) is common due to shared modes of transmission; mainly through unprotected sexual intercourse and exposure to contaminated blood products 6,7 . Current treatment options for HIV/HBV have a limited effect on HDV infection therefore not be adequate if there is HDV coinfection as response to HDV will not be achieved and liver disease progression continues to occur [8][9][10][11][12] . There is scarcity of data on HDV in Uganda.…”

Diagnosis, management and treatment of hepatitis delta virus infection: Turkey 2017 Clinical Practice Guidelines

“…The last acquiring virus has not been reported to suppress the previous virus or viruses (62). Dominant virus can also change its place in time (63,64). In general, the prognosis of triple virus infection is worse than a mono-infection.…”