Liver decompensation in HIV/Hepatitis B coinfection in the combination antiretroviral therapy era does not seem increased compared to hepatitis B mono‐infection

Abstract

Background & Aims HIV/hepatitis B virus (HBV) coinfected subjects are thought to have faster progression to end‐stage liver disease (ESLD) than HBV mono‐infected subjects. We assessed whether this remains in the current cART‐era. Methods Data from subjects with follow‐up completion post‐2003 were compared between HIV/HBV coinfected subjects in the Dutch HIV Monitoring database and HBV mono‐infected subjects from two centres. The primary outcomes of composite ESLD included portal hypertension, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation and liver‐related mortality. Outcomes were analysed using time‐dependent cause‐specific Cox regression models adjusted for follow‐up time and relevant covariates. Subset‐analyses were done in subjects with follow‐up pre‐2003. Results In the 1336 co‐ vs 742 mono‐infected subjects, coinfected subjects had no increased probability for ESLD compared to mono‐infected subjects (cHR 0.7 (95% CI 0.4‐1.1), but had increased probabilities for all‐cause (cHR 7.4 [4.9‐11.1]) and liver‐related mortality (cHR 3.4 [1.6‐7.5]). In the current combined cohort, treatment with tenofovir or entecavir was inversely associated with ESLD, all‐cause and liver‐related mortality (cHR 0.4 [95% CI 0.3‐0.7], cHR 0.003 [0.001‐0.01]), cHR 0.007 [0.001‐0.05]). Other predictors for ESLD were older age, being of Sub‐Sahara African descent, increased alanine aminotransferase levels and hepatitis C virus coinfection. While the probability for all‐cause mortality was increased in coinfected subjects, this rate decreased compared to pre‐2003 (HR 40.2 (95% CI: 8.7‐186.2). Conclusions HIV/HBV coinfected patients no longer seem to be at increased risk for progression to ESLD compared to HBV mono‐infected patients, likely due to widespread use of highly effective cART with dual HBV and HIV activity.

Impact of antiretroviral therapy containing tenofovir disoproxil fumarate on the survival of patients with HBV and HIV coinfection

“…The negative impact of HBV on the survival of HIV‐infected patients has been well demonstrated in previous studies, especially among those with higher HBV DNA load . HIV/HBV‐coinfected patients have 17 times higher risk for liver‐related mortality than those with HBV monoinfection despite effective HBV treatment . HIV coinfection worsens the natural history of HBV by accelerating the progression of HBV‐related liver diseases .…”

“…TDF‐containing cART has been recommended for HIV/HBV‐coinfected patients because TDF can achieve sustained viral suppression of both lamivudine‐susceptible and lamivudine‐resistant HBV, which subsequently improves liver fibrosis . Moreover, TDF‐containing cART has superior HIV virological response and better tolerability than other regimens containing zidovudine and abacavir .…”

Chronic Hepatitis B and HIV Coinfection: a Continuing Challenge in the Era of Antiretroviral Therapy

“…The authors postulated that the more widespread use of HBV treatment among PLWH on ART likely accounted for this protective effect but antiviral therapy was not captured in this study. A Dutch study however did capture antiviral therapy and found no significant difference in time to ESLD or all-cause death when comparing HIV-HBV-coinfected to HBV monoinfected individuals from 2003 to 2015 [39]. The findings from this study need to be interpreted with caution due to the substantial difference in follow-up between monoinfected and coinfected cohorts (median 3.8 vs 10.3 years with attrition of 40% vs 12% respectively).…”

Investigational drugs with dual activity against HBV and HIV (Review)

“…Numerous studies have proven the importance of dual activity drugs for coinfection treatment. Using highly effective cART with dual activity is able to significantly reduce the risk of developing end-stage liver disease in HIV/HBV coinfected patients (12). Interruption of HIV medications with anti-HBV activity in HIV/HBV coinfected individuals may result in HBV reactivation and/or hepatitis (13).…”