Antiretroviral therapy

According to updated WHO treatment guidelines, people with HIV and hepatitis B co-infection who have hepatitis B infection that requires treatment should also receive antiretroviral treatment with a regimen containing tenofovir and either 3TC or FTC, regardless of CD4 count.

US guidelines recommend that where hepatitis B treatment is indicated, co-infected individuals whould receive immediate antiretroviral treatment, regardless of CD4 count, with a combination containing tenofovir and FTC, while European AIDS Clinical Society guidelines recommend that antiretroviral treatment should begin at a CD4 count of 500 with a tenofovir-containing regimen.

An acute episode of hepatitis may occur in an individual with HIV / hepatitis B virus co-infection who is taking antiretroviral therapy. One study found that such flare-ups are very common among HIV / HBV co-infected people: over two years on HAART, 34% of co-infected people experienced acute hepatitis compared with 18% of people infected with HIV alone.¹

Liver toxicity may be caused by anti-HIV drugs. A number of antiretroviral drugs may cause elevations in liver enzymes, and people with viral hepatitis have an increased risk of liver toxicity. Full-dose ritonavir (Norvir), in particular, is associated with liver side-effects, but the lower dose commonly used to boost other protease inhibitors is less likely to cause toxicity.

The non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (Viramune) can cause a hypersensitivity reaction characterised by liver damage and skin rash. The protease inhibitor lopinavir/ritonavir (Kaletra) has also been linked to severe liver enzyme elevations, especially in people co-infected with hepatitis B or C.^{2 3} However, other drugs can also trigger liver toxicity including indinavir (Crixivan), sulphur-based antibiotics, ketoconazole (Nizoral), AZT (zidovudine, Retrovir), ddI (didanosine, Videx / VidexEC) and pentamidine (Pentacarinat).

HBV infection itself is a risk factor for the development of liver toxicity in people starting antiretroviral therapy. A major analysis of over 1840 patients enrolled in three major clinical studies found that people with hepatitis B or hepatitis C co-infection were almost five times more likely to suffer severe liver-related adverse reactions to antiretroviral therapy than those with HIV alone.⁴

An acute episode of hepatitis B may be the consequence of immune recovery. As HIV treatment improves immune function, this can lead to a form of immune reconstitution syndrome characterised by transient flares of liver inflammation and elevated liver enzymes as the immune system steps up its attack against hepatitis B virus in the liver.⁵ Some individuals who did not have them before may develop antibodies against hepatitis B virus. As a consequence, some experts believe that people with chronic hepatitis B infection who commence antiretroviral therapy should begin treatment for hepatitis B at the same time, in order to reduce the risk that antiretroviral therapy will lead to liver damage. If hepatitis flares up, antiretroviral therapy may need to be suspended temporarily while the hepatitis is addressed.

As noted above, stopping treatment with 3TC, FTC, tenofovir or entecavir can also lead to hepatitis B flare-ups. For this reason, some experts recommend that people should stay on these drugs even after their hepatitis B virus has developed resistance. In July 2004, the FDA mandated a change to the tenofovir label warning that the safety of the drug for the treatment of HIV / hepatitis B co-infection has not been established, and that severe acute exacerbations of hepatitis B had been reported in co-infected individuals who stop taking the drug. A similar warning is in place in the European Union, but tenofovir remains a recommended treatment option for co-infected patients.

Interruption of HIV treatment in people with hepatitis B carries an increased risk of death when compared to treatment interruption in those without hepatitis B. In the SMART study of HIV treatment interruption, co-infected patients had nearly a fourfold greater risk of death due to non-opportunistic disease compared with the rest of the study participants who did not have viral hepatitis. The main causes of non-opportunistic death among hepatitis B or C co-infected patients were substance abuse and non-AIDS defining cancers. Coinfected patients were also more likely to die of liver or kidney disease, although patients without hepatitis B or C were slightly more likely to die of cardiovascular disease.⁶

Despite the risk of an acute episode of hepatitis and/or elevated liver enzymes, evidence indicates that antiretroviral drugs may be safely used for people with viral hepatitis.⁷ However, dose reductions may be warranted due to poor liver function.