HIV prevented from entering the body
Microbicides that release antiretroviral drugs into the vagina or anus could neutralise HIV before it gets a foothold in the body.
Although oral administration of these drugs has in recent years downgraded HIV from a death sentence to a chronic medical condition, it is still described as one of the deadliest pandemics the world has ever seen.
In 2010, the Centre for the Aids Programme of Research in South Africa showed that a single antiretroviral drug delivered to the vagina or rectum during sexual intercourse could reduce HIV infection rates by close to 40 %.
Over the past five years, Professor Charles Kelly at King’s College London’s Dental Institute has coordinated the EU-funded CHAARM project to build on this and try to reduce infection rates even further with several antiretroviral drugs combined into a single, easy-to-use delivery method, such as a gel or a vaginal ring. This new form of prevention could boost the appeal and efficacy of microbidices among vulnerable communities.
Prof. Kelly explained that rectal and vaginal microbicides contain the same drugs that are used in systemic HIV treatments, but releasing them under more favourable circumstances could turn the tide in the struggle against HIV.
‘The difference is that by applying the drugs topically we can deliver higher doses of them with fewer side effects,’ he said. ‘Also, microbicides make it possible to hit the virus when it is vulnerable.’
Stopped at the gate
Tackling the process of infection erodes one of HIV’s greatest assets. In contrast to systemic treatments that have to combat generations of viruses that are already replicating inside the body, a microbicide limits to a single shot the chances of the virus getting past its defences.
‘If HIV is stopped at the gate, that’s the end of the infection,’ said Prof. Kelly.
Condoms remain the gold standard in terms of HIV prevention, but communities among which their use is inconsistent urgently need alternatives.
Discreet prevention methods such as microbicide gels and vaginal rings could offer millions of young women in lower income countries better chances to protect themselves against HIV infection.
If researchers can make microbicides that are both safe to use and accessible, these women could take charge of their own sexual health.
The work has also led to new discoveries about how drugs administered through the vagina enter the body and how to combine different drugs in a single gel.
Whereas the proteins that transport drugs inside and out of cells of the digestive and circulatory system are well documented, little was known about those in the vagina before the CHAARM project began.
‘We found, for instance, a protein that naturally pumped the drugs that we were testing out of vaginal cells,’ said Prof. Kelly.
To complicate matters further, the genetic adaptability of HIV limits the therapeutic effect of any single drug. Medical practitioners work around this challenge by administering different kinds of antiretroviral drugs at the same time.
Following the same strategy with microbicides means combining active chemical compounds while keeping their pharmaceutical effects separate. According to Prof. Kelly, this is no minor undertaking.
‘The two first antiretroviral drugs that we tested, Darunavir and Dapivirine, initially reacted in undesirable ways with each other,’ said Prof. Kelly. ‘They also responded in different ways to the medium within which we were formulating them.’
Rather than compromise on the active ingredients, CHAARM enlisted the expertise of Particle Sciences, a biotech firm in Bethlehem, Pennsylvania, in the US. The company developed a series of physicochemical tricks to combine the two drugs harmoniously.
These achievements were broadened to different kinds of antiretroviral drugs in the recently finished MOTIF project, also led by Prof. Kelly, which explored how optimised formulations and dosing could spread microbicides over all internal surfaces in the vagina and rectum, and into the human cells that need protection.
Notes to editors
“HIV prevented from entering the body” was originally published in the Horizon Magazine on May 4, 2016 and can be accessed here.
More information on the CHAARM project can be found on the European Commission website at: http://cordis.europa.eu/project/rcn/93644_en.html