Microbicides and Prevention

posted: 01/03/2011

There’s been much more progress in developing gels that help prevent HIV infection. The first trial of rectal use of a tenofovir microbicidal gel has produced useful results and boosted hopes.

Last year we heard of the first successful trial of a vaginal HIV prevention gel. Using this gel in the rectum for HIV prevention caused some side effects and may not be safe, the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, USA, has just heard. However the problems found are already being solved and new microbicides are under exploration.
 

80% preventive but few liked it
Although the gel was 80% effective in inhibiting HIV from infecting rectal cells, it caused stomach side effects as cramps and discomfort among some, and was unpopular, with only 25% of users liking it.
 

Next: 2nd attempt at anal gel
They are now working out a new version designed just for rectal use, and they are seeing if tenofovir can be given as a HIV prevention douche or enema.
 

Complex rectal microbicide study

• The study was complex and needed a lot of commitment from the 18 people who took part – all HIV-negative, 14 men and four women. First they had a single dose of oral tenofovir and then waited two weeks. During this time they had five rectal examinations and biopsies.
   
• Then they were either given one dose of either the CAPRISA tenofovir gel, or a placebo (fake) gel and again waited two weeks and had five more biopsies taken.
   
• Then, at last they were offered either the tenofovir or placebo (fake) gel once a day for seven days and had some final biopsies done.

Altogether 2000 biopsies were taken (they were very dedicated patients in this trial - on average each person had 111 biopsies!)
 

Why were there so many biopsies?
Somehow we need to test the gel against HIV in real life. The biopsies allowed the microbicide-treated cells to be kept alive in the laboratory to see how they respond to large doses of HIV. This is the closest we can get to doing the normal drug safety and safe doses tests.
 

Blood and rectal response
The researchers compared how much tenofovir was in the blood and rectal tissues after taking the pills and using the gel. Take the tablet and there was 30 times more tenofovir in the blood than after using the rectal gel, while using the gel meant there was 100 times more tenofovir in rectal tissues after just one rectal dose and after using it for 7 days it was 500 times higher. After seven days of rectal use HIV had 80% less viral infectivity.
 

Works, but side effects and unloved
So the gel shows signs of working well, but there were significant side effects and, perhaps most importantly, it was disliked by most.
 

Two volunteers reported grade three adverse events, meaning diarrhoea, cramps and discomfort. These were bad enough for the two to stop before completing the seven-day course. There were also some signs of cell damage being caused.
 

Only 25% of users said they liked the tenofovir gel, although 75% of people said they would be prepared to use it again if it proved protective against HIV.
 

Enemas and new versions, new microbicides
The tenofovir gel is now being reworked to be less toxic to cells.
The first trials of an enema delivering the anti-HIV drug involved nine gay men trying two different enema formulations and distilled water as the base for the enemas. Men preferred the enema which was designed to be in balance with the body (so it doesn’t draw out moisture from the tissues), and they found it went much further up the colon so would protect more, and found it was also the least toxic to cells.
 

Other experimental microbicides
Results for other experimental microbicides were also presented at the conference, including hi-tech ones containing broadly neutralising antibodies, which would act like a short-lived ‘mucosal vaccine’.
So there is more work to be done but microbicides are looking much more hopeful now than even 2 or 3 years ago.
 

Source with abstracts and references

Permalink

---