• The safety and toxicity of 0.1% UC-781 gel and 0.25% UC-781 gel administered intravaginally twice-daily for 14 days in sexually-active HIV-uninfected women
  
• and 0.25% UC-781 gel administered in sexually-abstinent HIV-infected women will be assessed by: macroscopic and/or microscopic evidence of vulvar and/or vaginal epithelium damage, including ulceration
  
• abrasion
  
• severe erythema
  
• and/or severe edema
  
• macroscopic and/or microscopic evidence of cervical mucosal damage including ulceration
  
• symptoms of genital irritation, including burning, itching or soreness
  
• laboratory evidence of grade 3 or higher toxicity for hematology, liver or renal function which cannot be attributed to another cause
  

• Acceptability of 0.1% and 0.25% UC-781 gel use by HIV-uninfected
  
• and 0.25% UC-781 gel use by HIV-infected women will be assessed by: proportion of participants who at Day 14 visit indicate they would be 'somewhat unlikely'
  
• or 'very unlikely' to use 0.1% and 0.25% UC-781 gel during sexual intercourse in the future compared to control gel users
  
• reported positive aspects of using 0.1% and 0.25% UC-781 gel compared to control gel users
  
• reported negative aspects of using 0.1% and 0.25% UC-781 gel compared to control gel users
  

Inclusion Criteria:

For All Females:

• Ages 18-45 years of age
• Able to provide written informed consent
• Normal Pap smear at screening or documentation of such within six months prior
• Regular monthly menses or amenorrhea due to hormonal contraceptive use
• Agree to pelvic exam, colposcopy and biopsy (if indicated) per protocol
• Able/willing to complete Study Diary
• Agree to abstain from sexual intercourse for 48 hours prior to the enrollment visit
• Agree to apply assigned study gel as required per protocol

• Agree to abstain from the following activities from at least 48 hours prior to enrollment through the Day 14 visit:

  • Insertion of fingers/objects into the vagina
  • Receiving oral sex
  • Receiving anal sex
  • Using a diaphragm, cervical cap, female condom, or vaginal contraceptive ring
  • Using vaginal products other than the study gels
  • Participating in other vaginal microbicide or contraceptive studies

Additional Inclusion Criteria for Stage 1:

• HIV-uninfected
• In a monogamous sexually active relationship with one male partner throughout the study
• Report having vaginal intercourse only with that partner at least two times per week
• Agree to use study-provided male condoms for each act of vaginal intercourse while taking part in the study
• Agree to inform male partner about participation

Additional Inclusion Criteria for Stage 2:

• HIV-infected
• Sexually abstinent or agree to abstain from sexual intercourse while taking part in the study
• Under regular medical care for HIV management
• CD4+ lymphocyte count > 200/mm3 for the last 6 months
• HIV viral load > 4.0 log10 copies/ml at screening
• Documentation of prior HIV genotype with one or more mutations conferring resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Not currently on antiretrovirals
• Willing to provide study staff with access to medical records related to their HIV infection

Inclusion Criteria for Male Partners:

• Ages 18 years or older
• Able to give written informed consent
• Male sexual partners of HIV-uninfected women taking part in Stage 1 of the study

Exclusion Criteria:

Exclusion Criteria for All Females:

• Are post-menopausal
• Have had a hysterectomy
• Clinically significant chronic medical condition (other than HIV) that is considered progressive.
• History of malignancy, with the exception of basal cell or squamous cell skin cancer
• Pregnant or planning to become pregnant in the next three months
• Currently breastfeeding
• History of sensitivity or allergy to latex or any compound used in this study
• Have received antibiotics in the 14 days prior to enrollment
• Have used a spermicide or spermicidally lubricated condom within 7 days prior to enrollment
• Have been using a hormonal contraceptive method for less than 3 months prior to enrollment
• Have participated in other microbicide or contraceptive studies in the past three months
• Grade 3 or higher liver, renal or hematology abnormality, as defined by the Table for Grading the Severity of Adult Adverse Events at screening
• Have a positive bacterial urine culture
• Currently have a clinically detectable genital abnormality (i.e. vulvar, vaginal, cervical and/or perineal ulcer or lesions or abnormal Pap smear)

• In the three months prior to enrollment have had any of the following:

  • An abnormal Pap smear
  • A pregnancy
  • An abortion
  • An intrauterine device (IUD)
  • Breakthrough menstrual bleeding
  • Vaginal bleeding during or following vaginal intercourse
  • Gynecologic surgery
  • Signs consistent with a sexually transmitted disease (STD)
  • Signs of genital trauma
  • Signs of genital tract infection other than asymptomatic bacterial vaginosis (BV)

• In the six months prior to enrollment have had any of the following:

  • History of treatment for or a diagnosis with a new STD
  • Exchanged sex for money, drugs or gifts
  • Protected (with condoms) penile-vaginal or penile-anal sexual contact with more than 4 partners
  • Unprotected (without condoms) penile-vaginal or penile-anal sexual contact with more than 1 partner
  • A male sexual partner who was diagnosed or treated for an STD (other than HIV)
  • A male sexual partner who has injected drugs
• Are currently using, or in the last year have used intravenous drugs (except for therapeutic use), crack or other recreational drugs
• Are currently abusing, or in the last year have abused alcohol.
• Any other condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives

Additional Exclusion Criteria for Stage 1:

• Unprotected (without condoms) or protected (with condoms) penile-vaginal or penile-anal sexual contact with an HIV-infected partner in the past 6 months
• Unwilling to use study-provided male condoms while on study

Additional Exclusion Criteria for Stage 2:

• NNRTI mutations in plasma and/or genital secretions at screening