Study of UC-781 Vaginal Microbicide

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