A Phase III, Multi-Centre, Randomized Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Immunodeficiency Virus Type 1 Infection in Women, and to Examine Effects of the Microbicide on the Incidence of Herpes Simplex Virus Type 2 Infection
A Phase III, Multi-Centre, Randomized Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Immunodeficiency Virus Type 1 Infection in Women, and to Examine Effects of the Microbicide on the Incidence of Herpes Simplex Virus Type 2 Infection
The purpose of the study is to assess the safety and effectiveness of intravaginal 1% tenofovir gel in preventing Human Immunodeficiency Virus (HIV-1) infection and Herpes Simplex Virus (HSV-2) infection in sexually active women.
This is a phase III, multicenter trial to assess the safety and effectiveness of 1% tenofovir gel, administered vaginally by approximately 2900 sexually active women at high risk for sexually transmitted HIV. Approximately 2600 women aged 18-30 years old will be enrolled to achieve the required number of endpoints to show an effect on HIV-1 infection, while up to 300 additional women aged 31-40 years old will be enrolled to collect more safety information in this age group.
This is an event driven study that plans to randomize seronegative women. Participants will be randomized to a 1:1 ratio to receive 1% tenofovir gel or placebo gel. Each will be asked to insert a dose of the assigned study product within 12 hours prior to a coital event and another dose as soon as possible within 12 hours after a coital event. Participants will be advised to use only two doses of gel in a 24 hour period.
All women will be evaluated for the rates of adverse events and the rate of HIV seroconversion. In addition, the study will evaluate several secondary endpoints that bear directly on potential risks and benefits of vaginal tenofovir gel use.
Inclusion Criteria:
Confirmed age 18-40 years (inclusive)
Able and willing to provide written informed consent
Able and willing to provide adequate locator information for study retention and safety purposes
Sexually active, defined as having had vaginal intercourse at least twice in the past 30 days prior to screening
HIV negative on two rapid tests performed by study staff within 30 days of enrolment (see algorithm in Appendix 3).
No evidence of glycosuria
No evidence of proteinuria greater than trace*
No history of pathological bone fractures
Have a negative pregnancy test
Women currently breastfeeding may be enrolled in the study
Agree to use a study-approved effective non-barrier form of contraception
Agree to adhere to study visits and procedures
Willing to use study gel as advised
Not using or taking any of the following groups of medications:
Exclusion Criteria:
History of adverse reaction to latex.
Plans any of the following during the study period
If in the opinion of the examining clinician, is not sexually active
Inadequate renal function (serum creatinine greater than 1.5mg/dl and creatinine clearance less than 50ml/min, as estimated using the method of Cockcroft and Gault96 )
Grade 3 and above ALT and AST at screening or any clinical sign of liver disease ( e.g. ascites, hepatomegaly, jaundice)
Abnormal serum phosphate levels (Grade 3 and above)
Has a clinically apparent finding on speculum pelvic examination (observed by study staff) involving deep epithelial disruption. Otherwise eligible participants with speculum pelvic examination findings involving deep epithelial disruption may proceed with enrolment after the findings have resolved and the inclusion/exclusion are met.
Received previously or receiving an experimental HIV vaccine
Currently participating in another HIV prevention intervention study or participation in any other clinical trial with a biomedical intervention in the last six months
Has current STI symptoms and/or other reproductive tract infection requiring treatment, as assessed by study staff. Otherwise eligible participants diagnosed during screening with infection(s) requiring treatment may be enrolled provided that treatment has been completed.
Any clinical evidence of untreated cervical abnormalities
Has any other condition that, based on the opinion of the Investigator or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.