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How do they work?

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How might microbicides work?

Researchers are exploring diverse and increasingly sophisticated ways to block HIV infection. These ways are called ‘mechanisms of action’. At this point, it is unknown which mechanisms of action and therefore which candidate microbicides will be able to reduce the risk of HIV transmission. Some candidate microbicides may even combine more than one mechanism. This fact sheet provides an overview of the mechanisms of action that are being explored and an overview of how microbicides are tested.

Early Clinical Research

Candidates in human trials between 2002-2009 worked by one of three main mechanisms:

  • Breaking up cell membranes (N-9, Saavy, Invisible Condom)
  • Enhancing vaginal defenses (Buffer Gel)
  • Blocking the virus from entering the genital mucosa (Carraguard, Cellulose Sulfate; PRO2000)

Current and Future Clinical Research

Most candidates currently in human trials are testing a new strategy – adapting existing ARV drugs for topical prevention. In other words, delivering highly potent antiretroviral drugs at the genital mucosa, where sexual transmission first takes place.

ARV drugs are already being used successfully to prevent mother to child transmission, and to reduce the risk of acquiring HIV after an accidental needle stick. They work in a variety of highly specific ways:

  • Targeting the virus and prevent it from attaching and entering white blood cells (the cells that HIV must infect in order to reproduce),
  • Blocking entry by targeting receptors on the outside of the white blood cell itself.
  • Preventing HIV from making more copies of itself (replicating) once it has entered a white blood cell.

ARV-based microbicides have certain advantages and certain limitations compared to candidates that work in other ways:

Advantages of ARV-based microbicides

Limitations of ARV-based microbicides

· May be highly effective against HIV

· Not contraceptive. Further study is required to see whether they could be combined with other agents to be or effective against other STIs.

· Daily or episodic use is possible; may be delivered through vaginal rings or other sustained release methods

· Not effective against other STIs

· Not contraceptive

· Further study is required to understand the potential for toxicity and dangers of HIV negative people taking ARVs

· Further study is required to understand whether users would develop resistance to ARVs if they became HIV positive whilst using the microbicide

Moving forward, it is important that research continue to find new microbicides candidates, especially those that may protect against other STIs in addition to HIV. The field must continue to innovate and broaden the pipeline of products under development.

Microbicides are scientifically achievable.

At least five international scientific meetings have concluded that microbicide development is both necessary and feasible [See timeline]. The Rockefeller Foundation convened a high level panel of scientists to evaluate the field and identify opportunities for accelerating microbicide science. The Scientific Working Group of the Rockefeller Initiative concluded:

Accelerating the development of microbicides is a realistic and important near-term opportunity. The challenges facing microbicide development are well understood and manageable. The first generation of microbicide products is now undergoing clinical testing, and, if effective, should be on the market well within this decade. Subsequent product generations will deliver improved effectiveness, a broader spectrum of activity, and enhanced acceptability for consumers.

For the entire Rockefeller report on science, click pdf

The pipeline of potential products is full and promising.

  • More than 50 product leads are under development
  • About a dozen of these products are currently in clinical trials
  • Only a few products are in phase II/IIB trials and phase III effectiveness trials (the last stage of testing)
  • The rest are in human safety testing

More on products in the pipeline...