Box 1 | The HIV/HBV overlap dilemma

Although it is estimated that about 5% of patients infected with HIV in the United States and Europe are co-infected with hepatitis B virus (HBV), the prevalence of co-infection is higher in the developing world, reaching 10% or higher in China and Southeast Asia. The RNA-dependent DNA polymerase (reverse transcriptase) of HIV and the DNA polymerase of HBV have functional similarity, and several antiviral nucleosides inhibit both enzymes and have clinical activity against both viruses. The list of drugs with overlapping specificity includes tenofovir, adefovir, lamivudine and emtricitabine.

One recent case series found that the anti-HBV nucleoside entecavir exerted anti-HIV activity in three co-infected patients being treated with entecavir alone, and promoted emergence of the M184V nucleoside resistance mutation in the HIV reverse transcriptase gene⁴⁵. These patients had a >1 log drop in plasma HIV RNA while taking no other anti-HIV drugs. This example raises concerns about using antiviral drugs with broad-spectrum activity in patients harbouring two or more chronic viral infections, which could promote drug resistance. An intriguing solution would be to require that anti-HIV regimens contain effective anti-HBV drugs, especially in areas where the prevalence of co-infection is high. Conversely, all patients being treated for chronic HBV might also need to receive drugs that will effectively block HIV replication. This strategy may be more attractive in the future if safe, effective and inexpensive overlap regimens can be developed. One possible outcome is that nucleoside and nucleotide reverse-transcriptase inhibitors could be avoided in regions with a high prevalence of HIV/HBV co-infection.

The RNA polymerase of hepatitis C virus bears little similarity to the HIV reverse transcriptase, and, aside from interferon- (IFN), there are, as yet, no approved drugs with overlapping clinical activity against these two viruses.