Safety and Acceptability of the Anti-Microbe Vaginal Gel, PMPA Gel

Inclusion Criteria All female participants may be eligible for this study if they: * Are between 18 and 45 years of age. * Have a menstrual cycle with at least 21 days between periods or have not menstruated for at least 6 months. * Agree from the time of Screening Visit until the Day 14 Follow-up Visit to: a) not use IV drugs (except for therapeutic use) and b) not participate in other microbicide or contraceptive studies. * Agree not to take part in the following activities for at least 48 hours before the study enrollment visit (Day 0) until the Day 14 Follow-up Visit: anal intercourse; douching; oral contact with the vagina; penetration of the vagina by fingers, sex toys, or any other objects; use of any vaginal product, including lubricants, drying agents, feminine hygiene products, diaphragms, and cervical caps. * Agree to insert the PMPA gel in the exact way it is specified. * Abstinent Women (Groups A1-A4, C, and V) may be eligible for this study if they: * Agree to abstain from vaginal intercourse from 48 hours before study until Day 14. * HIV-infected abstinent women (C) must be HIV infected; have a CD4 count of at least 200/mm3 at time of screening and within 6 months prior to screening, and a viral load of 10,000 copies/ml or less if on anti-HIV therapy or have a viral load of less than 55,000 if not on anti-HIV therapy; provide study staff access to HIV medical records and be under medical care for HIV management; and be on stable anti-HIV therapy (if any) for 1 month before screening and expect to stay on that therapy throughout the study. * Sexually Active Women (Groups B and D) may be eligible for this study if they: * Agree to abstain from vaginal intercourse for 48 hours before study start. * Agree to tell their mutually monogamous male sexual partner about their participation in the trial and of requirements from Day 0 until Day 14 to have vaginal intercourse at least twice weekly and to use a study-provided male latex condom for every sexual episode. * HIV-uninfected sexually active women (B) must currently have a single male HIV-uninfected sexual partner who is at low risk for HIV infection and who can be included in the study. * HIV-infected sexually active women (D) must have a CD4 count of at least 200/mm3 at time of screening and within 6 months prior to screening, and a viral load of 10,000 copies/ml or less if on anti-HIV therapy or have a viral load of less than 55,000 if not on anti-HIV therapy; provide study staff access to HIV medical records and be under medical care for HIV management; be on stable anti-HIV therapy (if any) for 1 month before screening and expect to stay on that therapy throughout the study; and currently have a single male HIV-infected sexual partner who can be included in the study. * Male sexual partners of sexually active participants (Groups B and D) must be: * At least 18 years old and in a relationship with the study participant for at least 3 months and be willing to maintain this relationship for the entire study. * At low risk for HIV infection and be HIV-uninfected if female partner is HIV-uninfected (B) or be HIV-infected if female partner is HIV-infected (D). * Able and willing to have vaginal intercourse with only the study participant at least 2 times per week, and to use study-provided lubricated male condoms each time during study. * Willing to not have vaginal intercourse for 48 hours before Day 0. * Willing to abstain from the following from 48 hours before Day 0 until the end of study product use: anal intercourse, oral contact with the vagina, and penetration of the vagina by fingers, sex toys, or any other objects. * Willing to take part in an interview after the study and undergo clinical evaluations. * (This study has been changed to expand the CD4 cell count criterion for Groups C and D.) Exclusion Criteria Female participants may not be eligible for this study if they: * Have gone through menopause. * Have had a hysterectomy. * Are breast-feeding. * Are using or have used within the past year IV drugs (except for therapeutic use). * Are pregnant. * Have serious liver, kidney, or blood problems. * Have had antibiotic therapy in the 14 days before study start. * Have taken part in other microbicide or contraceptive studies within 1 month of study start. * Have been previously enrolled in this study. * Have any genital abnormalities. * Are sensitive or allergic to any substances used in the study. * Are unwilling to use 1 of the following methods of contraception during the study unless surgically sterilized: non N-9 condoms, hormonal contraceptives, abstinence. * Have used any spermicide or condoms that have spermicide on them within 1 week before study start. * Have used a hormonal contraceptive method for less than 3 months before study start. * Have had any of the following in the 3 months before study start: vaginal bleeding during or following vaginal intercourse; breakthrough menstrual bleeding; an IUD; an abnormal Pap smear; a pregnancy; an abortion; or gynecologic surgery. * Have had, in the 6 months before study start, an STD or treatment for any STD, signs of an STD, or signs of genital tract infection. * Have any other condition that, in the opinion of the doctor, would be unsafe for the participant or would interfere with the study. * Male sexual partners may not be eligible for this study if they have: * Been treated for STDs or presumed STDs within 6 months before study start. * Symptoms of STDs that cannot be evaluated within 2 weeks of study start. * Sensitivity or allergy to any substance used in the study. * Any other condition that, in the opinion of the doctor, would be unsafe for the participant or would interfere with the study.