As well as providing a potent component of anti-HIV therapy, some drugs from the protease inhibitor class of antiretrovirals could also be an effective treatment for cervical cell abnormalities caused by cancer-causing types of human papilloma virus (HPV), according to research conducted at the University of Manchester. The research will be presented to the Twenty-third Papillomavirus Conference and Clinical Workshop in Prague on September 5th and a detailed paper has been accepted for publication in the September edition of Antiviral Therapy.
Investigators found that the protease inhibitors lopinavir and, to some extent, indinavir, killed cultured HPV-infected cells from the cervix. They are now looking to develop a topical treatment that can be applied to HPV-affected areas of the cervix.
Dr Ian Hampson of St Mary’s Hospital in Manchester told aidsmap that these findings were “very exciting.” His research team was originally interested in the apparent anti-HPV activity of indinavir (Crixivan), but they found that the concentration of the drug required for effective anti-HPV therapy was so high that it could not be practically used. They then looked at the ability of six other protease inhibitors to inhibit HPV and established that lopinavir was active against HPV in a low enough concentration for it to be used as a therapy against the virus. As an HIV therapy, lopinavir is boosted by a low dose of ritonavir (Norvir) and is marketed as Kaletra.
However, oral treatment with lopinavir would not provide a sufficient blood concentration of the drug to inhibit HPV so the Manchester investigators are now trying to develop a topical gel which would be applied to lesions in the cervix.
Coinfection with HPV is extremely common in HIV-positive individuals. A study conducted in the US recently showed that HIV-positive women are often infected with multiple cancer-causing strains of HPV some of which were not covered by the HPV vaccines currently in development. What’s more, research presented to last week’s International AIDS Conference in Toronto showed a high prevalence of high-risk HPV types and cervical cell abnormalities in women taking HIV therapy in Zambia and a significant increase in the incidence of anal cancer amongst French HIV-positive patients since effective anti-HIV treatment became available.
Dr Hampson believes a lopinavir-gel therapy for HPV could be particularly useful for resource limited settings, and added that although HPV vaccines were being developed, “not all lesions will be prevented, and not all women will be vaccinated.” It is likely that a gel would also provide a therapy for HPV infection and cancerous and pre-cancerous cell changes in the anus.
This is not the first time that a drug developed for anti-HIV therapy has found a use in another disease area with several anti-HIV drugs, as well as a failed anti-HIV drug, being used for the treatment of hepatitis B virus.