Baseline Predictors of High Adherence to a Coitally Dependent Microbicide Gel Based on an Objective Marker of Use: Findings from the Carraguard Phase 3 Trial.

A randomized, placebo-controlled, efficacy trial of Carraguard was unable to demonstrate a reduction in women's risk of HIV infection, which may have been due, in part, to low adherence (gel used in 42 % of vaginal sex acts, on average). A secondary analysis was undertaken to understand baseline factors associated with high adherence (gel used in ≥85 % of sex acts). Women who reported ≥1 vaginal sex act, returned ≥1 opened applicator, and had ≥1 conclusive post-enrollment HIV test (N = 5990) were included.

Microbicide product development.

Purpose Of Review: The purpose of this overview is to summarize the essential parameters needed to establish a sound microbicide development strategy.

Recent Findings: In recent years more comprehensive regulatory guidelines that are applicable to microbicides have been developed. Additionally, the US Food and Drug Administration have begun providing specific guidance for microbicide development.

Effect of sexual intercourse on the absorption of levonorgestrel after vaginal administration of 0.75 mg in Carraguard gel: a randomized, cross-over, pharmacokinetic study.

Background: The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner.

Study Design: This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application.

Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial.

Background: Female-initiated HIV-prevention options, such as microbicides, are urgently needed. We assessed Carraguard, a carrageenan-based compound developed by the Population Council, for its efficacy and long-term safety in prevention of HIV infection in women.

Methods: We undertook a randomised, placebo-controlled, double-blind trial in three South African sites in sexually-active, HIV-negative women, aged 16 years and older.

Effect of a single vaginal administration of levonorgestrel in Carraguard gel on the ovulatory process: a potential candidate for "dual protection" emergency contraception.

Objective: The study was conducted to evaluate the effect of Carraguard vaginal gel containing 0.75 mg of levonorgestrel (CARRA/LNG gel) administered in a single dose at different stages of follicle development over subsequent follicle rupture and hormonal levels.

Method: Randomized, blinded, cross-over study comparing the effects of a single administration of CARRA/LNG gel or Carraguard (CARRA) gel.

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.

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard gel: a new formulation for "dual protection" contraception.

Objective: The study was conducted to assess levonorgestrel (LNG) serum levels achieved after a single administration of two different doses of Carraguard vaginal gel containing LNG (CARRA/LNG), designed for use as microbicide and contraceptive for potential dual protection.

Materials And Methods: This was a randomized double-blind pharmacokinetic study conducted in 12 subjects enrolled at two centers. Each subject received a single vaginal administration of CARRA/LNG containing either 0.

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.