Determining the feasibility of utilizing the microbicide applicator compliance assay for use in clinical trials.

Introduction: Participant's adherence to use of study product is a major concern in microbicide clinical trials, which can impact on proving product efficacy. In a previously described assay, single-use microbicide applicators exposed to the vagina were tested by spraying the applicator with trypan blue dye, resulting in vaginal mucus staining on inserted applicators. As subjects in our Phase 3 trials return applicators only at quarterly visits, often mixing inserted and not-inserted applicators together in the same bag, cross-contamination could confound results.

Carrageenan/MIV-150 (PC-815), a combination microbicide.

Objective: The objective of this article is to study the effect of PC-815, a novel combination microbicide containing carrageenan and the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150, in blocking HIV-1 and HIV-2 infections in vitro as compared with Carraguard alone.

Goal: The goal of this study was to develop a combination microbicide that is more efficacious than Carraguard against HIV-1 and HIV-2.

Study Design: The microtiter syncytial assay was used to evaluate: 1) the antiviral and virucidal activity of MIV-150 against HIV-1MN; 2) the additive effect of MIV-150 when combined with carrageenan; and 3) a possible interference of seminal fluid in the antiviral activity of these compounds.

Lubricants containing N-9 may enhance rectal transmission of HIV and other STIs.

It has been shown that men who have sex with men actively seek lubricants that contain nonoxynol-9 (N-9) because they believe that N-9 may help to prevent infection by HIV. However, indirect evidence suggests that N-9 may actually enhance infection. Microscopic examination of rectal lavage and biopsy specimens collected at different time points following rectal application of a lubricant containing 2% N-9 showed rapid exfoliation of the rectal epithelium.

Assay for establishing whether microbicide applicators have been exposed to the vagina.

Objectives: To develop an accurate, rapid, and inexpensive method for verifying vaginal applicator use.

Goal: To develop a method for assessing compliance in microbicide clinical trials.

Study Design: Single use Microlax applicators containing a placebo formulation either were or were not exposed to the vagina.

The Development of Microbicides for Clinical Use to Prevent Sexually Transmitted Diseases.

Approximately 60 vaginal microbicides are under development for the prevention of HIV/AIDS and other sexually transmitted pathogens. The history and current status of the field are discussed with emphasis on the lessons learned from recent clinical trials, along with an emphasis on the mechanisms involved in the sexual transmission of HIV and how this information influences microbicide development. Additionally, the current status of in vitro and animal systems used for evaluating microbicide efficacy, as well as the challenges involved in developing more appropriate and practical assays, are discussed.