The majority of HIV infected people worldwide became infected with the virus through heterosexual contact. BufferGel and PRO 2000 Gel are vaginal gels designed to prevent women from becoming infected with HIV during sexual intercourse with an HIV infected partner. This study will test the safety and effectiveness of these gels.

Condition	Treatment or Intervention	Phase
HIV Infections HIV Seronegativity	Drug: BufferGel  Drug: PRO 2000/5 Gel	Phase II

Accessible, usable, and effective vaginal microbicides could significantly decrease the spread of HIV. Vaginal microbicides could be used with condoms to prevent HIV infection; they could also be used in situations in which an individual is unable to negotiate condom use. Vaginal microbicides are potentially bi-directional, preventing both male-to-female and female-to-male HIV transmission. This study will evaluate the safety and effectiveness of two vaginal microbicides, BufferGel and PRO 2000/5, in preventing the transmission of HIV. The study will also evaluate the effectiveness of these gels in preventing other common sexually transmitted infections (STIs).

BufferGel is a buffering agent designed to maintain normal vaginal acidity in the presence of ejaculate. Studies have shown that HIV is inactivated below a pH of 4 to 5.8. Carbopol 974, the major nonaqueous component of BufferGel, is commonly used as a gelling or tableting agent and has a well-documented safety record. BufferGel has proven safe and well tolerated in Phase I studies.

PRO 2000/5 inhibits viral entry into susceptible cells. PRO 2000/5 has also been evaluated in Phase I studies and was found to be safe and well tolerated.

Participants in this study will be randomly assigned to one of four study arms: BufferGel, PRO 2000/5, placebo gel, or no gel. All participants will receive HIV risk reduction counseling, condoms, and diagnosis and treatment of sexually transmitted diseases. Participants in the three gel arms will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of the product (BufferGel, PRO 2000/5, or placebo gel) intravaginally up to 60 minutes before each vaginal intercourse while in the study.

Participants will be enrolled for approximately 12 to 30 months, depending on when they enter the study. Participants will have two screening study visits and then monthly visits. Monthly study visits may take place at a clinic, the participant’s home, or other community site. Monthly visits will include a medical interview; urine testing, including pregnancy testing; HIV and STI risk reduction counseling; and distribution of study supplies (condoms and gel-filled applicators). Blood collection will occur at selected monthly visits. Four times a year, participants will be seen in the clinic for a more structured medical interview, pelvic exam, and HIV testing. The first 800 participants will have pelvic exams and HIV testing during their first 3 monthly visits; these participants will also be invited to join a colposcopy substudy.

Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• HIV uninfected
• Have had sexual intercourse at least once in the three months prior to study entry
• Of legal age to provide independent informed consent per local regulations and guidelines
• Able to provide adequate address information to study officials for purposes of follow up

Exclusion Criteria:

• History of adverse reaction to latex
• Nonmedical injection drug use in the 12 months prior to study entry
• Vaginal intercourse more than an average of two times per day in the 2 weeks prior to study entry
• Plan to become pregnant in the next 30 months
• Plan to travel away from the study site for more than 3 consecutive months in the next 30 months
• Plan to relocate away from the study site in the next 30 months
• Participation in another clinical trial of a vaginal product
• Pregnant within 42 days of study entry
• Have an STD or other reproductive tract infection diagnosed by study staff
• Have abnormal pelvic exam by study staff, indicating deep epithelial disruption
• Condition that, in the opinion of study officials, may interfere with the study

Anne Coletti, MS      781-779-1511    acoletti@fhi.org

Study chairs or principal investigators

Salim Abdool Karim, MBChB, PhD,  Study Chair,  University of KwaZulu-Natal   

Study ID Numbers:  HPTN 035
Record last reviewed:  August 2004
Record first received:  December 11, 2003
ClinicalTrials.gov Identifier:  NCT00074425
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-20