The purpose of this trial is to determine whether using the diaphragm and a lubricant get can reduce women''''s risk of acquiring an HIV infection.

Condition	Intervention	Phase
HIV Infection	Device: Ortho All-Flex diaphragm and Replens lubricant gel	Phase III

Further Study Details: 

Primary Outcomes: HIV incidence
Secondary Outcomes: STI incidence (CT, NG, syphilis, trichomoniasis, HSV2); acceptability; feasibility and sustainability
Expected Total Enrollment:  5000

This multi-site randomized, controlled trial will measure the effectiveness of the diaphragm in preventing heterosexual acquisition of HIV infection among women. This Phase III study is powered to detect effectiveness (biological efficacy combined with adherence) of 33 percent. Women in South Africa and Zimbabwe (N=4,500) at risk of contracting HIV will be invited to participate and will be followed for up to 24 months, with a total study duration of 4 years. All women will receive safer-sex counseling, free male condoms and diagnosis and treatment of sexually transmitted infections (STIs). Half of the participants will be randomly selected to receive an Ortho All-Flex latex diaphragm and Replens lubricant gel. We will assess whether women using diaphragms and lubricant gel have lower rates of HIV or STI infection than do their non-diaphragm and gel counterparts. Additionally, we will investigate the long-term acceptability of the diaphragm in this study population.

Ages Eligible for Study:  18 Years   -   49 Years,  Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Age 18 to 49 years old
• Sexually active (coital frequency at least four times per month on average)
• HIV negative based on testing within two weeks prior to enrollment
• Chlamydia trachomatis and Neisseria gonorrhoeae negative based on testing within 30 days prior to enrollment or if positive, completes treatment before enrollment
• Have a healthy cervix, as assessed by naked-eye speculum exam at enrollment
• Planning to live in the study area for the next 24 months
• Willing to be randomly assigned either to use or not use a latex diaphragm with lubricant gel during participation in the study, and to follow the protocol, including being tested for HIV and STIs
• Willing and able to give informed consent

Exclusion Criteria:

• Known sensitivity or allergy to latex
• History of TSS (as suggested by current labeling for diaphragm use)
• Currently pregnant, or desiring to become pregnant in the next two years
• No cervix (total hysterectomy)
• Refuses treatment for diagnosed or suspected current STI and/or reproductive tract infection requiring treatment at enrollment
• Within six weeks of any pelvic surgery or last pregnancy outcome at the time of screening and enrollment
• Presence of clinically apparent lesion(s) with epithelial disruption at enrollment (may enroll after lesion(s) has healed, if otherwise eligible)
• Injected illicit drugs in the 12 months prior to screening and enrollment
• Blood transfusion or received blood products in 3 months prior to screening and enrollment
• Unable or unwilling to insert the diaphragm correctly
• Participation in any other clinical trial (including those of a vaginal product or barrier contraceptive). Verification by comparing participant lists to other concurrently running research studies may be conducted if necessary.
• Unable to speak English, Zulu, Shona, or Sotho
• Other conditions that, in the opinion of the investigator, would constitute contraindications to participation in the study or would compromise ability to comply with the study protocol, such as a major psychiatric disorder

Please refer to this study by ClinicalTrials.gov identifier  NCT00121459

Heidi Fancher      415-597-9193    hfancher@psg.ucsf.edu
Ann Brown      617-349-0040    abrown@ibisreproductivehealth.org

South Africa, Gauteng
      Perinatal HIV Research Unit, Soweto,  Gauteng,  South Africa; Recruiting
South Africa, KwaZulu Natal
      Medical Research Council of South Africa, Durban,  KwaZulu Natal,  South Africa; Recruiting
Zimbabwe
      UZ-UCSF, Harare,  Zimbabwe; Recruiting

Study chairs or principal investigators

Nancy Padian, PhD,  Principal Investigator,  University of California, San Francisco   
Gita Ramjee, PhD,  Principal Investigator,  Medical Research Council of South Africa   
Taazadza Nhemachena, MD,  Principal Investigator,  UZ-UCSF   
Guy de Bruyn, MD, MPH,  Principal Investigator,  Perinatal HIV Research Unit   
Kelly Blanchard, ScM,  Principal Investigator,  Ibis Reproductive Health   

Study ID Numbers:  H6070-22217-03
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 20, 2005
ClinicalTrials.gov Identifier:  NCT00121459
Health Authority: United States: Institutional Review Board; South Africa: Medicines Control Council
ClinicalTrials.gov processed this record on 2005-07-26