The lemon gel debate

As researchers around the world dismiss claims lemon juice offers a practical solution to preventing HIV-infection, a Kenyan researcher has developed a microbicide from it. Is this line of research a waste of time? Wandera Ojanji finds out.

Dr Kizito Lubano, a researcher

The development of antiretrovirals (ARVs) has had a remarkable contribution in the management of HIV/Aids. Of higher significance has been the adoption of antiretrovival therapy (ART), which has improved the health and wellbeing of people living with HIV/Aids.

With major strides being recorded in post-infection management of HIV/Aids, preventing transmission altogether has remained one of the biggest challenges in the war against HIV/Aids. Many admit that abstinence is a difficult concept to sell successfully. Many argue that for adults, and especially those in marriage, sex is part of life and must be enjoyed.

Prevention measures against HIV transmission will have to revolve around development of a vaccine or target the main mode of transmission — the sexual act. However, experts estimate that it will take 15 to 20 years to have an effective vaccine in the market. The most practical medical onslaught against HIV infection is therefore to find ways to prevent transmission during sex.

So far, the condom remains the most effective weapon against HIV transmission during sex. The male condom, if used correctly and consistently, is 98 per cent effective against HIV infection according to Dr Kizito Lubano, Technical Advisor, Global Aids Programme, Centres for Disease Control and Prevention, Kenya.

Empowering women

But women, who are the most vulnerable, have limited control over the use of the male condom. A safe and easy to use substance that would reliably protect the vagina from HIV infection and prevent pregnancy would therefore be a great empowerment to women. It is out of this realisation that researchers worldwide turned their attention to developing a product — a microbicide — that women can use without necessarily seeking the permission of the man or one that will not turn off the man.

One line of investigation, a vaginal gel that incorporates neat lemon juice and can prevent HIV infection during sex and also prevent pregnancy. Scientists around the world have considered and rejected the idea. But now, a Kenyan researcher is trying to revive it by developing a product called UniPron. The microbicide has been developed by Dr Gichuhi Mwethera, a senior reproductive health scientist at the Institute of Primate Research (IPR), a World Health Organisation collaborative biomedical research centre. IPR is also a member of the European Union Primate Vaccine Evaluation Network, which sets the standards and guidelines for working with non-human primates.

Dr Mwethera, who developed the product in collaboration with a local drug manufacturing company, Universal Pharmaceutical Corporation, has patented the product with the Kenya Industrial Property Institute. He intends to patent it in the West and India to protect it against piracy.

Acidic environment

Dr Mwethera says preliminary research findings in animals confirm that lemon juice can be effective against HIV infection and pregnancy. He observes that when they administered neat lemon juice into a baboon’s vagina, it "killed the HIV virus" and sperms deposited by the male baboon.

Dr Gichuhi Mwethera, who has patented UniPron, a microbicide.

Dr Mwethera explains that the science behind lemon juice is simple. Lemon juice is very acidic, with a pH level of about 2. The HIV virus and sperms cannot survive within an acidic environment. The optimum pH for survival of HIV virus and sperms is between 7.2 and 7.4. Lemon juice simply makes the vagina too acidic.

What is novel about it is the way it has been formulated and packaged.

"We have increased the pH to about 4. This is to ensure that the product remains potent but does not damage the vaginal wall," explains Mwethera.

However, HIV/Aids and reproductive health experts are divided on the efficacy and safety of Dr Mwethera’s innovation. There are those who strongly feel it has great potential in prevention of HIV and pregnancy. Others feel it stands little chance for it is likely to be counterproductive.

Dr John Skibiak of Population Council, Kenya, is sceptical of use of lemon juice as a microbicide in preventing HIV infection during sexual intercourse. He dismisses it as lacking any scientific merit, has no basis for assuming effectiveness and may even spiral HIV infection.

"Lemon juice is very acidic and therefore very caustic. Using it will cause damage and lesions to the sexual organs. The broken wall or the lesions open up routes for HIV infection."

Risks of lemon juice

He further argues that gels are no longer widely used even as contraceptives since studies discovered that users risked developing lesions, especially if used in high doses.

Scientists from the US-based CONRAD programme at the Eastern Virginia Medical School warn women against using lemon or lime juice for purpose of preventing HIV infection or pregnancy. They base their warning on a six-day study of 47 women who were asked to apply one of three concentrations of lime juice — 25 per cent, 50 per cent and pure or water to their vaginas. The results showed that anything more concentrated than 50 per cent can cause serious damage to the cells that line the vagina. This could make it easier for the virus to get in.

According to an article published in SciDev, Christine Mauck who led the study, feels no further money should be spent on safety and efficacy trials for lime juice, a conclusion that others at the Microbicides 2006 conference in Cape Town, South Africa agreed with.

But Dr Lubano believes the product has great potential to turn around the war on preventing HIV infection and pregnancy for it is tailored around the natural systems in the vagina to prevent infection. By nature, the vagina is acidic. The acidity is produced by beneficial bacteria in the vagina and this helps to naturally prevent infection, he explains.

"During sexual intercourse, the vaginal discharges reduce the acidity of the vagina to levels where a sperm can survive. Unfortunately, the favourable pH for sperm survival is also favourable for the survival of HIV virus. The lemon juice will help maintain or enhance the acidity of the vagina, killing the HIV virus and also the sperm," he says.

Preclinical studies

But he is quick to add a word of caution.

"Normal acid produced by the vagina is OK. Introducing unnatural acid, added to friction during sex is likely to weaken the protective surface of the vagina or break the vaginal wall. And this may likely increase the chances for HIV infection and other diseases."

Dr Mwethera and fellow researchers are now moving on to the next stage — preclinical studies — to test the safety and efficacy of lemon juice in baboons before starting clinical studies in humans. In addition to safety and effectiveness, the researchers will also be looking for acceptability of the gel among the targeted users.

And preclinical testing of UniPron has been made easy for Mwethera. Dr Moses Otsyula, a virologist at IPR and one of the leading HIV/Aids researchers in the region, has already developed an animal model for testing UniPron.

"This model can be used to test microbicides, vaccines and drugs that need to be applied through the vagina."

The model uses baboons which, according to Dr Otsyula, are closer to humans both physiologically and immunologically and even from a reproductive stand point.

Effect on the body

Dr Lubano states that the success of the product will be governed by a number of factors, which the researchers must address. There is need to test for safety, allergy and feeling of the gel even before they think of incorporating the active ingredient.

An issue they have to address is the acceptability of the product by the end-users, especially whether it creates a too watery or too dry environment to cause discomfort during sex or otherwise. Women will shun it if it has the tendency to leak, contaminate or stain garments, observes Dr Lubano.

"People want to be as natural as possible during sex. The product should not be so obvious as to deviate people’s minds away from the business at hand. The idea is to empower women with a product they have control over but one, which is not so obvious to the man like the female condom."

According to Dr Mwethera, the gel should be able to be applied 12 hours before or even just before sex and not be noticed by the man. The other concern that needs to be addressed is the effect of the microbicide on the physiological activities of the body. For instance, should the woman want to get pregnant, she should be able conceive without complication. Is there a chance that the spermicide can mess up with the sperm, resulting in a deformed baby?

Unwarranted criticism

He says these are the same concerns that have made other contraceptives either fail or succeed. Foaming tablets were not acceptable because they made the vagina too watery. They were, however, 60 to 70 per cent effective contraceptives. The female condom, which is 95 per cent effective in preventing pregnancy, is not widely used because it is believed to be too cumbersome to insert and too noisy during sex.

Dr Lubano believes the criticisms against the product are unwarranted for now.

"It may not be perfect, but a good starting point for there is always room for improvement. Like any other microbicide being developed, it may not be 100 per cent effective, but will be used in conjunction with other HIV/Aids management regimes."

He argues that UniPron is one of the promising microbicides being researched under the coordination of the International Partnership for Microbicides (IPM). There are first, second and third generation microbicides, whose active ingredients are based on synthetic chemical compounds. The fourth generation and the most promising microbicides are being developed with the active ingredient being similar to antiretroviral drugs.

The successful development of a microbicide will go along way in reducing infections, especially among women who are the most vulnerable. In Kenya, 70 per cent of people infected with HIV/Aids are women, a proportion that is rising, according to Dr Lubano. In 1998, women only accounted for 55 per cent of those infected with HIV. This is due to their biological vulnerability where women are three to four times at risk of being infected than a man.

Funding and pricing

Dr Mwethera, whose main research interests have revolved around strategies to prevent HIV infection and development of a vaccine to prevent HIV infection, acknowledges that for UniPron to be accessible to majority of Kenyans, it must be well priced.

This is not the first time Dr Mwethera is working on microbicides. In 1995, he identified two proteins — Fertilin and EPPIN — from human sperms whose initial studies clearly showed that they could be developed as contraceptive vaccines. This was part of his PhD work. "Unfortunately, the two proteins have since been patented in the West with very little acknowledgement of my contribution," he laments.

Funding may be the biggest hurdle in the development of UniPron and making it available to Kenyans. Dr Mwethera, who has been researching on UniPron for over two years, says he requires about Sh20 million for the remaining phases of research and development. But as researchers worldwide focus on developing a microbicide, they have to grapple with the fact that for now, there are no set standards for the efficacy of the microbicides.

"This is the scientific challenge we face. There is need to develop criteria that defines the acceptable standard for microbicides," he adds.

With Kenya allocating a mere 0.3 per cent of its Gross Domestic Production to research and technology, the private sector may be the only hope for researchers and especially when it comes to key innovations that have potential for high financial returns, says Mwethera.