Rectal microbicides - lubes with anti-HIV properties now in development

[IRMA]

Hello

Wanted to share a little info on rectal microbicides with guys on this site. Rectal microbicides are lubricants or gels that have anti-HIV properties - they are in the research and development phase now and do not actually exist outside the context of clinical trials.

IRMA stands for International Rectal Microbicide Advocates - we are a global network of more than 1200 advocates, scientists, policy makers and funders pushing for the development of safe, effective, acceptable and accessible rectal microbicides for human beings who have anal sex. Acknowledging that many people can't use condoms, or don't want to use condoms, rectal microbicides could provide protection against HIV (and hopefully other STDs) in the absence of condoms.

Quick facts:

• Many rectal microbicides currently being tested contain some of the same drugs, called antiretrovirals (ARVs), used to treat HIV.

• Microbicide development began over 20 years ago and originally focused on anti-HIV products for vaginal use. The field is now also testing rectal products for use during anal sex. The goal is to develop products that have activity against HIV and other STDs as well - though the current batch of products are primarily anti-HIV focused.

• Rectal microbicides are currently being tested in a gel/lubricant form. Other formulations being considered are douches/enemas.

• No microbicide – vaginal or rectal – has been proven effective against HIV to date; therefore, microbicides currently being tested are only available to volunteers taking part in clinical trials . No microbicide is on the market.

For more background on rectal microbicides visit the Microbicide Trials Network at: www.mtnstopshiv.org/node/2864 and IRMA at www.rectalmicrobicides.org.

IRMA co-produced a video called "The Rectal Revolution is Here: An introduction to rectal microbicide clinical trials" and can be viewed here: http://tinyurl.com/RectalRevEnglish. It is a good intro to the field and the clinical trial process.

A new Phase II rectal microbicide trial, testing safety and acceptability, is starting soon - mid 2013. Sites for the trial are in Thailand (Bangkok and Chiang Mai), Peru (Lima), South Africa (Cape Town) and the United States (Boston, Pittsburgh, San Francisco - as well as Puerto Rico.) The trial is called MTN 017 and will be testing a gel with the drug tenofovir in it. The study won't prove whether the gel works, but is the precursor to moving into a larger scale, Phase III efficacy trial designed to show whether the microbicide actually works to prevent HIV or not. More info on MTN 017 can be found here: http://www.mtnstopshiv.org/news/studies/mtn017/backgrounder

This is a lot of info - so will stop here. Am happy to answer any questions anyone may have.

Thanks

Jim Pickett

IRMA chair

[rawTOP]

Thanks so much for posting this. I've been curious about microbicides as a form of HIV prevention...

A few questions...

• Many rectal microbicides currently being tested contain some of the same drugs, called antiretrovirals (ARVs), used to treat HIV.

That's a bit of a bummer since I was hoping microbicides would be an alternative to ARVs.

How much of the ARV gets absorbed into the body? Do you know or is there a theory on it? To what degree are microbicides like taking ARVs? Or is the idea to put ARVs at the point of infection only and not have them circulating in the body generally?

Is there a risk the person will become resistant to the ARV? Irregular use of ARVs has led to meds-resistance in the past - just wondering if this is a concern - or is this one of the questions they're looking at with the current trials?

• No microbicide – vaginal or rectal – has been proven effective against HIV to date

Can you qualify that statement a bit? Is it a matter that there have been few if any Phase 3 trials? Or have there been trials that have failed? I think I heard of one vaginal trial that failed. Have there been any Phase 3 trials for anal microbicides? I guess what I'm getting at is there's a big difference between not proving efficacy yet and trying and having failed. Which of those better describes where thing stand?

A new Phase II rectal microbicide trial, testing safety and acceptability, is starting soon - mid 2013. Sites for the trial are in Thailand (Bangkok and Chiang Mai), Peru (Lima), South Africa (Cape Town) and the United States (Boston, Pittsburgh, San Francisco - as well as Puerto Rico.) The trial is called MTN 017 and will be testing a gel with the drug tenofovir in it.

If you would like banner ad space on this site to recruit volunteers when the trial starts, just let me know. I'll be happy to provide it free of charge.

[IRMA]

That's a bit of a bummer since I was hoping microbicides would be an alternative to ARVs.

How much of the ARV gets absorbed into the body? Do you know or is there a theory on it? To what degree are microbicides like taking ARVs? Or is the idea to put ARVs at the point of infection only and not have them circulating in the body generally?

Is there a risk the person will become resistant to the ARV? Irregular use of ARVs has led to meds-resistance in the past - just wondering if this is a concern - or is this one of the questions they're looking at with the current trials?

Can you qualify that statement a bit? Is it a matter that there have been few if any Phase 3 trials? Or have there been trials that have failed? I think I heard of one vaginal trial that failed. Have there been any Phase 3 trials for anal microbicides? I guess what I'm getting at is there's a big difference between not proving efficacy yet and trying and having failed. Which of those better describes where thing stand?

Going to try an and answer all the above.

At the moment, the microbicide field is heavily into ARVs, and yes, that is a bummer - but not the end of the story.

The reason the field is so focused on ARV-based microbicides is due to the fact that a number of other, non-ARV agents were tested in vaginal microbicide trials (including an agent based on seaweed called Carraguard) - up to an including Phase III efficacy trials - and they all were shown not to work. The field has been existence for more than 2 decades. The very first vaginal microbicide trial to show efficacy was a trial called CAPRISA 004. It took place among women in South Africa, and reported modest efficacy - around 39% - of a tenofovir-based gel that was applied before and after sex. The trial announced results in 2010. Another trial in South Africa, called FACTS, is now underway to attempt to confirm the CAPRISA results, using the same dosing regimen of applying the gel before and after sex. A complicating factor here is that another trial, called VOICE, was testing the DAILY use of tenofovir gel among women in several African countries in one arm of a huge multi-pronged trial. The gel arm had to be stopped due to "futility" - regular checks of the data by an outside group called the Data Safety Monitoring Board determined that the trial could never show whether the gel worked or not. So, essentially, the arm was halted because daily use of tenofovir gel among women in the trial was shown to have no protective benefit.

Another reason the field of new prevention technologies is so interested in ARVs is that Truvada as PrEP (oral pill taking) has been shown to work in a number of populations.

There have been no Phase III efficacy trials of rectal microbicides. The Phase II trial - MTN 017 - I mentioned is the very first Phase II trial (safety and acceptability) for rectal microbicides ever. It is hoped that this trial will be successful, and set the stage for a Phase III, or Phase IIb (both can show efficacy) trial.

Regarding trials "failing." We tend not to see a trial every "failing." If it is ethically and scientifically sound, any trial always answers a question. It may not be the answer you wanted, but it answers the question nonetheless. Products do fail - and as I said, there have been several failed products.

In terms of absorption - ARV microbicides tend to stay where you put them. So there is not very much systemic absorption going on - tends to stay in the vaginal tissues, or the rectal tissues. This is a good thing, because that is where infection happens. And low systemic absorption reduces the chances of resistance or toxicities. This isn't theoretical, there is science to back this up. Microbicides with ARVs in them also contain very little drug - nothing like the amount you would take as part of a triple combination therapy for HIV treatment. Still, people who are positive should not take ARV-based microbicides for two reasons. One, if they are on treatment, the drug in the microbicide could interfere. Two, if they are not on treatment, the presence of essentially sub-optimal therapy could create problems of resistance (this issue is being studied.) When ARV-based microbicides have been shown to work and are in the "real" world - ppl will need to test for HIV three to four times a year, to ensure they remain negative. And if they should test positive, stop taking the ARV microbicide right away - to reduce chances of potential resistance.

One thing to point out, if you take an ARV-based microbicide "irregularly" - whatever that may mean - and you remain HIV negative, you cannot become resistant to the drug. Resistance is only a concern when the person is HIV+ and using the ARV microbicide.

While ARVs are dominating the microbicide landscape right now - there is a desire among scientists and advocates to look at other agents that are not ARV. That is happening. There is a strong desire to develop microbicides that are multi-purpose - that protect against HIV and other STDs, and for women, that are contraceptive. Microbicides with just ARVs in them won't be "broad spectrum." HIV poz people should have microbicides as an option to protect their partners too. And, lots of folks just won't want to use an ARV microbicide.

Regarding your offer to place banner advertising for the MTN 017 trial. I will let the sites and investigators know of your offer - all of whom I will be seeing in the next week. Very nice of you to offer. IRMA is an advocacy org - we don't actually conduct trials.

Okay, hope I answered your questions. Let me know if I missed something, or if you have follow-ups.

In the meantime, I am going to give you a couple more links, since you are so interested in rectal microbicides.

The first is to an IRMA report published in 2010 called "From Promise to Product: Advancing Rectal Microbicide Research and Advocacy." It provides a great overview of the science and advocacy as of 2010 - and still remains relevant.

And last year, I wrote an article for USAID caleld "Ready, Set, Rectal Microbicides" which is a much more concise, and briefer overivew of the science.

Jim

[rawTOP]

Jim - Thanks so much for those clarifications. The fact that the ARVs are low-dose and not really absorbed too much sounds great. I'm not a big fan of "better living through chemistry", but microbicides sound like a form of PrEP I could support.

As far as banner ads for recruitment, whatever people may think of this site, we have some of the highest risk people as members. Our members will therefore be some of the best test subjects since they take (willingly) on far more risk than the average guy.

[IRMA]

As far as banner ads for recruitment, whatever people may think of this site, we have some of the highest risk people as members. Our members will therefore be some of the best test subjects since they take (willingly) on far more risk than the average guy.

I totally agree with you. New prevention technologies like PrEP and microbicides are not being developed for people who consistently use condoms after all. If human beings loved condoms so much and were willing and able to use them all the time - we'd have no HIV epidemic. And we wouldn't have spent decades and BILLIONS of dollars to find alternatives methods of protection.