A new study conducted at nine US medical centers has concluded that the FDA-approved oral anti-HIV drug tenofovir (Viread) is also safe when applied as a vaginal microbicide gel. Microbicides are designed to prevent the sexual transmission of HIV and other sexually transmitted diseases and are formulated as vaginal gels, foams, creams, or suppositories.

Currently, there is no microbicide available that has been approved for widespread use. The aim of the current study, published in the February 28, 2006 issue of AIDS, was to establish the highest practical dose and frequency (HPDF) of 0.3% or 1% tenofovir vaginal gel applied once or twice daily by sexually abstinent, HIV-uninfected women. In addition the study sought to assess the safety, tolerability and systemic pharmacokinetics of the HPDF in abstinent and sexually active HIV-negative and HIV-infected women.

Eighty-four women used the study product for 14 consecutive intermenstrual days. Safety laboratory assessments and pelvic examinations were performed during five study visits, with colposcopy at enrollment and on day 14. Samples for pharmacokinetics were collected before and after the initial tenofovir gel use and at day 13.

Results

·         The 1% tenofovir gel used twice daily was as well tolerated as other regimens used by the 48 HIV-negative sexually abstinent women.

·         Although 92% of the women reported at least one adverse event, the majority were mild (87%) and involved the genitourinary tract (70%).

·         One possibly product-related severe adverse event involving lower abdominal cramping was reported by a sexually abstinent woman who used 0.3% gel twice daily.

·         Serum tenofovir levels were low but detectable in 14 of the 25 women.

·         No new HIV RNA resistance mutations were detected after 2 weeks of tenofovir gel in the 24 HIV-infected participants.

In conclusion, the authors write, “A 2-week course of 1% tenofovir vaginal gel used twice daily was well tolerated in sexually abstinent and sexually active HIV-negative and HIV-positive women. Systemic tenofovir absorption occurred. Expanded safety and effectiveness testing is warranted.

“A safe and effective topical microbicide would offer women an HIV prevention method that they could control,” said lead author Kenneth Mayer, director of the Brown University AIDS Program.

“The data will pave the way for further studies that will ultimately evaluate whether the gel protects women from HIV infection,” says co-author Lisa Maslankowski, MD, medical director of the HIV prevention research division at the University of Pennsylvania School of Medicine. “As the first investigational microbicide to contain an antiretroviral agent, tenofovir gel can prevent HIV from replicating, unlike other microbicides which have been designed to block HIV entry into cells, or have other mechanisms of action.”

02/23/06

Reference
K H Mayer and others (for the HPTN 050 Protocol Team). Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 20(4): 543-551, February 28, 2006.