Rectal microbicides (currently under development) are products that could take the form of gels or lubricants – being developed to reduce a person’s risk of HIV or other sexually transmitted infections (STIs) through anal receptive sex. Rectal microbicide research is progressing ahead with a thrust presently. One of the phase-I study results presented by scientists at the International Microbicides Conference (M2012) in Sydney, Australia, is all set to enter Phase-II because of the positive study outcomes in phase I. This study called MTN-007 (phase I) evaluated the rectal safety of a reformulated version of tenofovir gel. It has found that tenofovir gel was both safe and acceptable.
The results of the study which included 65 HIV-negative men and women who used the gel rectally once a day for one week, represent an important step forward in the effort to develop a rectal microbicide to prevent HIV through anal sex.
This MTN-007 study was conducted at three US sites as a follow-up to an earlier study that had assessed the rectal use of the original vaginal formulation of tenofovir gel. Although that study found the gel had a significant antiviral effect in rectal tissue, its use was associated with gastrointestinal side effects, including diarrhoea. To make the gel more suitable for rectal use, researchers reduced the amount of glycerin – a common additive found in many types of products – so that less fluid would be drawn from cells. Indeed, the current study found rectal use of the reduced glycerin formulation was better tolerated than the vaginal formulation.
Plans are now to test this ‘rectal friendly’ version of tenofovir gel in a phase II trial that will involve 186 men who have sex with men (MSM) and transgender people at clinical sites in Peru, South Africa, Thailand and the US, said Dr Ian McGowan, Co-Chair of M2012, and Co-Principal Investigator, Microbicides Trials Network (MTN), University of Pittsburgh, USA.
“This reduced glycerin formulation of tenofovir gel was very well tolerated, people had minimal side effects and people seemed to be happy using the product. We also looked at the effect of this gel on the rectal mucosa, although generally it looked very safe, however, upon closer lab studies when we studied change in any of the genes, we found that tenofovir gel changed the expression of about 600 different genes (out of 44,000). This change in gene expression upon closer evaluation might have caused an immune response and also a change in mitochondrial activity. Whether it will be a problem clinically, we have no idea as the gel is so well tolerated by study participants, but we have to look at this in future studies” said Dr Ian McGowan.
Long way to go still as phase II is about to begin, yet it gives hope as products such as rectal microbicide, once developed in safe and effective forms, could possibly meet the unmet need of HIV prevention of millions of MSM and transgender populations across the world.