Objectives: 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, and to evaluate the safety, tolerability and systemic pharmacokinetics of the HPDF in abstinent and sexually active HIV-negative and HIV-infected women.
Methods: Eighty-four women, enrolled in sequential cohorts, used the study product for 14 consecutive intermenstrual days. Safety laboratory assessments and pelvic examinations were carried out 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, establishing the HPDF. 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. No significant systemic toxicity was detected.
Conclusion: 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.
From the aMiriam Hospital/Brown University, Providence, Rhode Island and Fenway Community Health, Boston, Massachusetts
bUniversity of Pennsylvania, Philadelphia, Pennsylvania
cFred Hutchinson Cancer Research Center, Seattle, Washington State
dHarlem Hospital Center and Columbia University, New York
eBronx-Lebanon Hospital Center, New York
fFamily Health International, Arlington, Virginia
gJohns Hopkins University, Baltimore, Maryland
hGilead Sciences Inc., Foster City, California
iNational Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Received 18 July, 2005
Revised 13 September, 2005
Accepted 3 October, 2005
Correspondence to Dr Kenneth H. Mayer, The Miriam Hospital, 164 Summit Avenue, Providence, Rhode Island 02906, USA. E-mail: Kenneth_Mayer@brown.edu