19-Oct-2011 - HIV infection is commonly associated with other sexual infections, such as herpes simplex virus (HSV). Infection with HSV facilitates the risk of HIV infection and negatively impacts the clinical course of HIV disease. Therefore, it would be highly beneficial to identify multi-faceted microbicide compounds that are efficient against HIV-1 and other sexually transmitted infections.
Now, a new study published by Cell Press in the October 20th issue of the
journal Cell Host and Microbe explains why a change in the delivery method
of an established anti-HIV drug results in dual protection against both HIV and HSV.
The research is the result of an international collaboration between Belgian,
Italian and American laboratories; senior authors Prof. Jan Balzarini from
the Rega Institute for Medical Research in Belgium, Prof. Carlo-Federico
Perno from the University of Rome "Tor Vergata" in Italy and Dr. Leonid
Margolis from the National Institute of Child Health and Human
Development, Bethesda, MD, USA.
There has not been much success in generating new clinically useful microbicide
compounds, so, recently, a substance called "tenofovir", which has been widely used in
HIV therapy as an oral tablet, was formulated as a topical vaginal gel and tested in a
large study of nearly 900 South African women. Tenofovir works by inhibiting an enzyme
that HIV needs to make copies of itself. Surprisingly, not only did the microbicide
significantly reduce HIV-1 transmission, it also caused a dramatic reduction in the
risk for infection with HSV.
The effect of tenofovir gel on HSV was unanticipated because the drug had previously
shown very minimal activity against HSV. "We hypothesized that the discrepancy between the
earlier reported lack of significant anti-HSV activity and the new data might be
explained by the striking differences in drug concentrations between the oral
tenofovir delivery system and topical application of the gel," explains
Prof. Balzarini and colleagues demonstrated in a variety of experimental models
that when tenofovir was applied at concentrations similar to those obtained in the gel,
the drug had a potent and direct anti-HSV activity. The researchers went on to unravel
the molecular mechanism of the anti-HSV activity and found that, like the effect on
HIV, tenofovir efficiently inhibits an enzyme needed for herpes viral replication.
Taken together, the results demonstrate that topical administration of tenofovir
achieves drug concentrations that exert both anti-HIV and anti-HSV activity. "Our data
and the therapeutic principles emerging from our study are important for the design
of new drug formulations and administration protocols to develop and/or optimize
future microbicide trials," concludes Dr. Margolis.
Elisabeth (Lisa) Lyons