Viral Hepatitis Co-Infection

HIV patients who are co-infected with hepatitis B (HBV) or hepatitis C virus (HCV) are at higher risk of adverse effects or antiretroviral therapy (ART)

Since most antiretroviral drugs are metabolized in the liver (mainly
through the cytochrome P450 system), any liver disease might
impair this metabolism of antiretroviral drugs (ARVs) and increase the
risk of hepatotoxicity and other adverse effects of ART.

Facts about ART and hepatitis co-infection

  • HBV and HCV co-infected patients have a higher risk of ART-related hepatotoxicity compared to HIV mono-infected patients
  • ARVs associated with hepatotoxicity are stavudine, didanosine, nevirapine, ritonavir boosted tipranavir and daruanvir
  • The risk of hepatotoxicity correlates wth the stage of liver fibrosis
  • Sustained HCV clearance after interferon-based therapy reduces the risk of subsequent ART-related hepatotoxicity
  • HCV co-infected patients are more likely to discontinue ART due to a broad range of toxicities

The risk of ART-related adverse effects are often not well studied in hepatitis co-infected patients since they are typically underrepresented in randomized clinical trials.

Hepatitis flares in HBV patients on ART
Immune reconstitution inflammatory syndrome (IRIS) is sometimes described in HBV co-infected patients who initiate ART with a low CD4+ cell count. Patients can experience increased liver enzymes and sometimes symptomatic hepatitis.

Clearance of HBV and normalization of liver enzymes can sometimes be seen.

HBV patients who interrupt ART with anti-HBV activity (lamivudine, emtricitabine or tenofovir) are at risk of liver enzyme flares and clinical hepatitis which occasionally can be life-threatening.

Patients who use lamivudine as a single active anti-HBV drug are at high risk of selection of resistance mutations and development of hepatic flares. This is of particular concern in low- and middle-income countries where the access to more potent tenofovir-based ART is limited.

Beneficial effects of ART on the liver of coinfected patients
Despite the increased risk of hepatotoxicity and other adverse effects of ART, ARVs are usually safe for co-infected patients.

Observational trials have found an inverse relationship between low CD4+ cell counts and risk of advanced liver fibrosis and/or liver-related complications and death.

In some studies of HIV/HCV co-infected patients, protease inhibitor based combination antiretroviral therapy (cART) has been associated with slower fibrosis progression compared with those who received no therapy or other ART regimens.

Other studies have found that HCV co-infected patients with undetectable HIV viral load had slower fibrosis progression compared with patients who had any detectable viral load.

Regression of advanced fibrosis has been described in HIV/HBV coinfected patients on long-term HBV suppressive therapy.