Intensification with pegylated interferon during treatment with tenofovir in HIV–hepatitis B virus co‐infected patients

Abstract

In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (-0.066 vs -0.027 PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.

Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

“…Some of the more recent therapeutic strategies evaluated during HBV mono-infection have included add-on with peg-IFN after exposure to NA [ 107 , 108 ] or interruption of anti-HBV therapy [ 109 ]. No beneficial effect of peg-IFN intensification after TDF initiation has been observed in HIV-HBV co-infected patients [ 110 ], while treatment interruptions are generally discouraged due to their associated risk of hepatic flares and increased morbidity [ 16 , 111 ]. Since residual ccc-HBV DNA and integrated HBV DNA remain present in the hepatocyte after loss of HBsAg, discontinuation of anti-HBV treatment, particularly under immune suppression, could reactivate HBV [ 112 ] and thus anti-HBV-containing ART might be required despite functional cure.…”

Research gaps in viral hepatitis

“…Current therapeutic strategies have been engineered to affect both innate (toll‐like receptor agonists) and adaptive (checkpoint inhibitors) arms of the immune system, but again are mostly experimental . Considering that these approaches may require a highly orchestrated immune response, as is the case with interferon‐based therapies , their efficacy could be reduced in immunocompromised HIV‐HBV co‐infected patients .…”

HIV-hepatitis B virus coinfection

“…Limited studies of interferon have been performed in HIV-HBV co-infected individuals since the widespread availability of HBV-active ART, but recent studies have shown that the addition of pegylated interferon to HBV-active ART in HBeAg positive co-infected individuals did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels during treatment [172, 173] .…”