Sunday Times (Johannesburg) - April 30, 2006
Claire Keeton

"We have been tinkering with normal bugs so that they secrete an anti-HIV substance," said molecular biologist Dr Dean Hamer of the US National Institutes for Health.

The novel concept attracted attention this week in Cape Town at Microbicides 2006, the world's fourth conference on microbicides.

Microbicides in the form of a gel, cream, sponge, ring or suppository are inserted prior to sex and release an active ingredient which can kill or inactivate HIV cells during intercourse, explained conference co-chairman, Professor Helen Rees from Wits University.

Hamer's experiments using a genetically modified E.coli Nissle to block HIV have worked in the lab, and shown promising results among mice and in rectal tests on four out of eight monkeys.

To be effective, the modified bacteria must be able to endure in the body after the initial dose and keep producing a protective substance.

Active ingredients in current microbicides range from seaweed extracts, which trials have proved to be safe, to high concentrations of lime juice, which have been rejected after harming the vagina.

The approach of using "live" protein-based microbicides is a leap forward in their development.

If it proves to be successful, then, in theory, sexual partners could pass on to each other genetically modified (GM) "bugs" that protect against HIV.

But, given the widespread resistance to eating GM food, the concept of introducing modified "bugs" into the gut or the rectum is likely to be controversial - and regulatory approval could be challenging.

Hamer has been manipulating E.coli Nissle, which abound in the intestines, to make a protein to stop HIV from getting into cells.

The modified E.coli are used in a rectal microbicide to block HIV infection during anal sex, which, Hamer said, was "a major route of HIV transmission for men having sex with men, and also for heterosexuals since the HIV risk is so much higher [than during vaginal sex]".

Dr Laurel Lagenaur of the US National Institute of Allergy and Infectious Diseases, and "bacterio-therapeutics" company Osel, is modifying Lactobacilli jensenii for use as a vaginal microbicide.

The Lactobacilli are a natural defence in the vagina and women are more vulnerable to HIV and sexually transmitted infections when they are deficient.

Lagenaur said: "The genetically manipulated Lactobacilli will deliver an anti-HIV protein.

"In mice experiments, these modified bacteria multiplied in the vagina, kept their important characteristics and were longlasting.

"They also succeeded in blocking Simian Immunodeficiency Virus infection in both vaginal and rectal [tests] in monkeys."

But, despite the potential of such microbicides, Hamer emphasised that they are still in the early stages and only condoms are proven to protect against HIV.

The advantage of microbicides over condoms, speakers at the conference said, is that women can control their use when they are unable to insist on condoms.

In the past two years microbicide research has increased dramatically. About 12000 women in South Africa are currently testing the effectiveness of five out of six "second generation" products in clinical trials.

The development of microbicides includes:

•The first generation, which was effectively detergents intended to kill the virus; these included nanoxynol-9, known as N9, which proved disastrous in trials since it increased the risk of getting HIV instead of offering protection;

•The second generation of products which work by stopping the virus from attaching to the cells, or preventing it from multiplying once it has entered a cell; and

•The future generation, to prevent HIV using combinations of antiretroviral drugs, currently used to treat people with Aids.

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