Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women.
OBJECTIVE
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.


CONCLUSIONS
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.
Mayer
Kenneth H
KH
Miriam Hospital/Brown University, Providence, Rhode Island 02906, USA. Kenneth_Mayer@brown.edu
Maslankowski
Lisa A
LA
Gai
Fang
F
El-Sadr
Wafaa M
WM
Justman
Jessica
J
Kwiecien
Antonia
A
Mâsse
Benoît
B
Eshleman
Susan H
SH
Hendrix
Craig
C
Morrow
Kathleen
K
Rooney
James F
JF
Soto-Torres
Lydia
L
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010349:Patient Compliance; D012746:Sexual Abstinence; D000068698:Tenofovir; D014622:Vaginal Creams, Foams, and Jellies
D019380:Anti-HIV Agents; D063065:Organophosphonates; D014622:Vaginal Creams, Foams, and Jellies; D000068698:Tenofovir; D000225:Adenine