Acyclovir: The Next New HIV Drug?

In two poster presentations at CROI 2009 in Montreal, Canada, acyclovir, a drug used to treat herpes, shows that it also inhibits HIV during the reverse transcription (RT) step in the virus's life cycle. Two studies looked at how acyclovir affected the RT enzyme, which may pave the way to using the drug to treat HIV infection either on its own or together with herpes therapy.

In the first study, in an attempt to find compounds with novel anti-HIV activity, a team from John Hopkins School of Medicine and Howard Hughes Medical Institute searched through nearly 3000 FDA-approved drugs or other drugs in phase II studies. Twenty were found to have moderate activity against HIV and 18 were selected for this study.

In the lab, CD4 cells were infected with HIV and then exposed to 10 mM of acyclovir. Cultures were also individually exposed to the other 17 compounds. Viral load tests were done to assess the reduction of HIV levels. Other tests were used to confirm whether the RT enzyme was the drug's target. Herpes infection and activity were also examined. Acyclovir, along with the other compounds, was shown to suppress HIV replication.

The second study looked at the activity of acyclovir on HIV in various tissues from the tonsils, lymph nodes, rectum and genital tract, all co-infected with various human herpes viruses. After treating HIV-infected cells with acyclovir, viral loads and RT activity were assessed.

If the cells had both HIV and herpes viruses in them, then acyclovir suppressed HIV reproduction in those cells. Conversely, if the cells didn't have herpes virus in them, then acyclovir didn't suppress HIV. However, when cells infected with herpes virus only were added to treated co-infected cell cultures, then acyclovir suppressed HIV again. This suppression of HIV appears to affect HIV that uses both R5 and X4 co-receptors.

More study is needed to discover how acyclovir interacts with HIV, both with and without the presence of a herpes infection. One main concern here is how acyclovir may affect HIV mutations. For example, when people with HIV are simply treating their herpes and not their HIV, they may actually be on "HIV monotherapy" which may then lead to poorer HIV therapy outcomes. This data comes in light of reported studies from CROI 2008 that showed using acyclovir in herpes-infected individuals increased the risk of HIV infection.