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

The purpose of this study is to evaluate the PMPA gel, which kills microbes, in HIV-infected and HIV-uninfected women. The majority of new HIV infections occur through heterosexual contact. A product that stops or slows the replication of HIV during sexual contact is needed. At present, there are no products that are completely effective. PMPA gel, also known as tenofovir, is an anti-microbe agent that may fight against sexual transmission of HIV and other sexually transmitted diseases (STDs). It is applied to the vagina and gives women the ability to control their disease-prevention activity.

The majority of new HIV infections are transmitted through heterosexual contact. Currently, there is no single product that is completely efficacious in preventing initial HIV infection through vaginal transmission. Thus, the development of a topical product which could block local virus replication once infection has occurred is needed. Topical microbicides are designed to prevent the sexual transmission of HIV and other disease pathogens. Potentially, they can be applied vaginally to prevent both male-to-female and female-to-male transmission. They also offer a female-controlled option. PMPA gel has shown some activity against HIV and STD pathogens in in vitro and in vivo laboratory studies. Participants undergo eligibility screening tests which include: a general physical exam; a pelvic exam; a urine pregnancy test; urinalysis; HIV and STD testing and counseling; and hematology, liver, and renal function tests. For HIV-infected participants, a CD4 cell count is performed and specimens are collected for quantitation of HIV viral load in plasma and cervico-vaginal fluids. \[AS PER AMENDMENT 05/29/02: and for HIV resistance genotyping.\] PMPA gel is evaluated among 4 types of women distributed into 7 cohorts. All participants apply PMPA gel intravaginally for 14 consecutive intramenstrual days. The dose and frequency of application is escalated across "cohorts." Cohorts A1 through A4 consist of HIV-uninfected, abstinent women who use different doses of PMPA gel once or twice daily. Cohort B includes HIV-uninfected women who are sexually active. Cohorts C and D consist of HIV-infected women who are abstinent or sexually active, respectively. Cohorts B, C, and D use the highest practical dose frequency. The male partners of sexually active participants undergo HIV and STD testing and counseling as well as an optional genital exam and a post-regimen interview. Participants keep a daily record of when doses are taken and of any adverse effects. Pelvic exams, and hematology, liver, and renal function tests (and CD4 cell counts \[AS PER AMENDMENT 05/29/02: and resistance genotyping\] in HIV-infected participants) are performed at follow-up visits. After the regimen is complete, participants participate in group interviews to discuss adverse effects, adherence to, and general perception of PMPA gel. The first 6 participants in Cohorts A2, B, and C take part in a pharmacokinetic (PK) study of PMPA gel. Serum collection and PK analysis are performed at different time intervals during 2 study visits.