Council Commentary

Griffithsin: A promising non-ARV microbicide

Much-anticipated results from the first in-human clinical trials of griffithsin, a naturally occurring anti-HIV protein, were presented at the HIV Research for Prevention (HIV R4P) conference in Madrid this October.  These results, and research to date, suggest that it may be possible to formulate an on-demand user-controlled technology to prevent HIV and other STIs with limited risk of cross resistance.

We asked Tom Zydowsky, director of biomedical research and pharmaceutical development in the HIV and AIDS program at the Population Council’s Center for Biomedical Research (CBR) a few questions about griffithsin and its potential as a non-antiretroviral microbicide.

Q: Can you tell us more about Griffithsin—what is it and what is its origin?

A: Griffithsin (GRFT) is a pharmaceutical that we are looking at as a potential microbicide to prevent HIV and other sexually transmitted infections. Specifically, it is a safe, potent, and broad-spectrum protein that binds to sugars on the outside of cells thereby preventing HIV from entering target cells and replicating. Griffithsin, which comes from a red algae found off the coast of New Zealand, is now being manufactured in rice and tobacco plants through a cost-effective engineering process that allows us to study its potential for microbicide development and commercialization.

 

Q: Tell us - why you are so excited about Griffithsin?

A: Griffithsin has great potential as a multipurpose technology – or MPT. It has the potential to prevent HIV and other STIs – in both men and women – without the worry of cross-resistance seen with antiretrovirals. Research has shown that in cell-based assays, human tissues and animal tests, GRFT can prevent HIV, herpes simplex virus type-2 (HSV-2), human papillomavirus (HPV), and hepatitis C.

Unlike most HIV prevention drugs in development, GRFT is a non-ARV inhibitor of HIV, which means that it does not inhibit steps in the HIV lifecycle within cells. 

 

Q: Why do you think Griffithsin has potential as a multipurpose prevention technology?

A: When combined with carrageenan, a natural product derived from seaweed with potent activity against HPV, cell-based tests revealed that the combination has better antiviral activity against HSV-2 and HPV than either compound alone. We also found that a griffithsin/carrageenan (GRFT/CG) combination gel product could prevent HSV-2 infection in mice better than either compound alone.

Recently, our research has shown that, when formulated as a fast-dissolving insert and applied vaginally, GRFT/CG has the potential to prevent HIV, HSV-2, and HPV infection in animals. We are working now to test the addition of a contraceptive to the GRFT/CG combination so that we could potentially develop a contraceptive multipurpose technology that targets both STIs and pregnancy.

 

Q: Why did the Council choose to investigate this compound?

A: Much of the microbicide/multipurpose technology field has been and is currently focused on ARV products. We decided to buck that trend and enter the less crowded non-ARV space to potentially offer safer, more convenient, and more cost-effective HIV/STI prevention options to men and women. The Council had not worked on protein-based inhibitors previously, so our scientists were eager to explore this new class of inhibitors and expand the tools in our chemistry toolbox. We chose to explore griffithsin because it’s a safe, broad spectrum, non-ARV inhibitor that has potent activity against ARV-resistant HIV strains.

 

Q: Why would a non-antiretroviral be an important compound to add to the HIV prevention toolbox?

A: HIV prevention products containing a non-ARV inhibitor like griffithsin would complement the ARV-based product offerings and provide advantages that might make the non-ARV griffithsin product more accessible and acceptable to users. Use of ARVs for HIV prevention requires HIV screening before and during use, which may pose a barrier to access in low-resource/high-demand settings and lead to HIV-resistant infections if ARV products are used by HIV positive individuals. A non-ARV microbicide could eliminate the need for HIV screening, help to reduce the emergence of drug-resistant HIV types, and be provided over-the-counter once safety in HIV-infected individuals is demonstrated.

 

Q: Why should the sexual and reproductive health community be excited about the potential of a griffithsin-based multipurpose technology?

A: In only five years of studying griffithsin, we were able to complete the first-in-human clinical trial of the compound, and we found that a gel containing griffithsin/carrageenan (GRFT/CG) gel is safe for vaginal use for up to 14 days.

There were no safety signals, and no GRFT was detected in plasma. This valuable clinical experience with a GRFT microbicide sets the stage for our next proposed clinical study: a Phase 1 study to test the safety, pharmacokinetics/dynamics, and acceptability of a GRFT/CG fast dissolving insert for use at or around the time of sex. We are also developing a sustained-release product for women who want continuous protection from HIV and other viral pathogens.

 

Dr. Zydowsky oversees four laboratories dedicated to understanding the biological mechanisms by which HIV and other sexually transmitted infections are acquired and progress to develop multipurpose prevention technologies (MPTs) that deliver both microbicides and contraceptives.  His lab has been studying GRFT since 2013 and multipurpose prevention technologies generally for more than 11 years.

To learn more about the Council’s biomedical research, visit www.popcouncil.org/cbr.