Microbicide Effects on Efficacy, Safety, Innate Immunity

Project: Research project

Project Details

Description

Heterosexual transmission of HIV is the primary route in women, who now account for 50% of those infected.
In the absence of an effective vaccine, other modes of prevention are needed. A safe and effective topical
microbicide will allow women and men to play a more direct role in their own protection. As with therapeutic
approaches to HIV, a topical microbicide that combines compounds with differing modes of action will have
an advantage in blocking the complex interactions that occur in the mucosa at the time of transmission.
Many women at risk who will use the compounds will not know their HIV status. Therefore, a microbicide
approach must consider the impact of exposure of infected women to the compound and therefore topicals
that do not represent major therapeutic antiretrovirals might be an advantage. Given the evidence that HSV
enhances HIV transmission, agents that also impact on other STI will have an added benefit. This approach
must be safe and not interfere with natural barriers to infection. The approach to the advancement of
candidate microbicides proposed in this program takes into account each of these issues. We are proposing
to advance the development of the novel compound SAMMA to formulated product that will include an acid
buffer to combine the entry inhibitory activity of SAMMA with the direct effects of an acid pH on the virus.
We will also explore the potential of other compounds such as novel persulfated molecular umbrellas (pmu)
as well as cdk inhibitors. Both classes of compounds have activity against HIV and HSV. Each of these
approaches will be carefully studied focusing not only on advancing candidate compounds but broadening
our understanding of the interaction between critical host defenses and topical microbicides. Carefully
planned pilot clinical evaluation of compounds already in clinical trials (cellulose sulfate, acidform and
tenofovir) as well as the proposed formulated SAMMA will focus on the effects of these compounds on
innate immunity as well as the development of surrogate markers for efficacy.
StatusFinished
Effective start/end date9/3/102/29/12

Funding

  • National Institute of Allergy and Infectious Diseases: $410,188.00

ASJC

  • Drug Discovery
  • Infectious Diseases
  • Molecular Medicine
  • Virology
  • Pharmacology

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