African Woman and Child Feature Service

Scientists are following with keen interest an HIV positive pregnant woman who has managed to control the amount of the virus in her body at undetectable levels for the past nine years without being on drugs.

Now four months pregnant, doctors want to see if she can deliver an HIV negative baby without using ARVs or caesarean section, the key interventions used to significantly cut-down the chances of the mother transmitting the virus to her unborn baby.

“Since she conceived, we are doing CD4 and viral load tests in close frequencies to establish how they are performing before we decide how she will deliver,” says Dr Surendra Patel, an expert in infectious diseases at MP Shah Hospital.

“If the viral load remains undetectable as it is now, then there will be no justification to intervene with antiretroviral or caesarean section during birth.”

Her CD4 count- immune cells used to fight infections- is 1,200 and the viral load is below 40 copies/mL, the level at which the virus is defined as undetectable. CD4 count for an HIV negative healthy individual is over 410.

The woman is one of the seven other HIV positive persons who have managed to keep the virus at undetectable levels many years after being infected.

A similar phenomenon is being studied by scientists at the Kenya Aids Vaccine Initiative (Kavi), where out of the more than 200 people that have been followed for several years, three of them may hold key to the development of a broadly neutralising antibody vaccine.

“So far we have managed to isolate few individuals who have very promising results and now they are being studied to understand how their immune system is able to neutralise the virus,” says Prof Omu Anzala, a virologist and Kavi Director.

This new phenomenon is being seen in both men and women who have been screened by Kavi in Nairobi.

Dr Patel has been following his patients for over five years to establish what makes them tick.

“These individuals have neither used any antiretroviral drugs nor been attacked by opportunistic infections despite living with the virus,” he says.

Of the eight people, one has CD4 count of 1,800, with the viral load below 40 copies or undetectable level.

“In the next 18 months, we hope to complete the follow-up and issue a statement on our findings,” says Dr Patel.

These cases are what have come to be known as the Elite Controllers-people whose immune system is able to control the HIV viral load to less than 40 copies/mL compared to over 30,000 copies/mL of HIV in a person without such antibodies.

Only five percent of all the HIV infected persons globally, are categorised as elite controllers. Kenya is one of the countries with some. They are of two types.

One is the Aviramic Elite Controllers, whose viral load is always undetectable. The other is the Viramic Elite Controllers, whose viral load has stabilised at about 1,000 copies.

Because of the undetectable viral load, those infected are unable to transmit the virus to their partners.

Scientists strongly believe with such an ability to stop the virus from infecting new cells, these people could hold the key to developing an effective AIDS vaccine.

Studies in the primates have already shown that broadly neutralising anti-bodies to possess the ability to prevent infection.

The Director of the National Aids and STD Control Program (Nascop), Dr Ibrahim Mohamed, said the government is aware of a cohort of HIV positive persons with stable CD4 count and a low viral load who may not need any intervention for now.

“There are long-term non-progressors who are able to manage the virus without our intervention with antiretroviral drugs.”

The reasons as to why these people are able to manage the virus without medications are varied, he adds.

He thinks besides producing neutralising antibodies, the virus these people have might have mutated to develop into a weaker virus that is unable to replicate, or their CD4’s do to have receptors.

The latter are specific sites on the CD4 cell which HIV uses to bond and infect the cells. Without them, the virus is disabled. In fact, some of the ARVs are known to interfere with this process making it difficult for the virus to enter the cell.

These are areas Prof Anzala says the University of Nairobi is currently studying to better understand the virus.

In 2008, his team at Kavi announced that it had identified 10 Elite Controller with powerful antibodies that neutralise the virus. On being screened, the individuals were found to possess high CD4 count and very low viral loads-amount of HIV in the body, which were uncharacteristic of an infected person.

They also had very low possibilities of transmitting the virus to another individual and progressing to AIDS, the last stage of the disease where opportunistic infections reign, killing the individual if not well managed.

Those screened at Kavi have been found to possess an immune system able to elicit antibodies – CD4 and CD8- with a unique protein that target specific sites of HIV stopping it from infecting new cells.

In the African region, of the 1,700 HIV positive people who have been screened in Kenya, Uganda, Rwanda, South Africa, and Zambia, 170 have HIV neutralising antibodies.

“What we are experiencing now is phenomenal and provides critical information of how we move forward and the massive work we need to undertake in this direction,” says Dr Wayne Koff, of International Aids Vaccine Initiative (IAVI).

Scientists at IAVI, which has invested millions of shillings in research around this new phenomenon, say they have managed to identify four antibodies with the ability to neutralise the virus.

Now they are studying them to see which ones are broadly neutralising-those with ability to neutralise different types of HIV strains such as A, B, C and D, which are also circulating in Kenya.

IAVI has set aside between 30 and 50 per cent of its budget on vaccine discovery on the identification and development of a vaccine with the ability to elicit these antibodies. They have also developed what they call Protocol G, whose sole objective is to help scientists identify elite controllers across Africa and other parts of the world.

Identifying and understanding the broadly neutralising antibodies as the most effective way of preventing HIV infection remain the most difficult thing for the scientific community.

Scientists admit that HIV is tricky to contain because of its HIV immune evasion mechanisms, is sexually transmitted, and has high capacity of recombination, among other factors.

Addressing scientists in one of the forums held in recent times in Nairobi, Dr Koff admitted that “as a field we have not understood as yet how to elicit broadly neutralising antibodies to tackle HIV.”

The closet the scientists came to generating neutralising antibodies was during the Vaxgen vaccine trials. It never worked. The vaccine failed to elicit such antibodies in amounts necessary to control HIV infection.

But even with recent encouraging findings about elite controllers, much needs to be done to develop an effective vaccine. Whereas neutralising antibodies are required to work on various sites of the virus to disable it completely, the ones discovered so far work only on one site of HIV.

Unlike the cellular immune response-where the immune system cells identify and kill the already infected CD4 cells; the neutralising antibodies maybe superior as they are able to prevent the virus from infecting the cell in the first place.

Still, scientists believe a vaccine that produces both broadly neutralising antibodies and cellular immune response would be the most effective way to control the virus.

This encouraging information has lead IAVI to establish Neutralising Antibody Consortium, whose sole responsibility is pick-up more antibodies with ability to prevent HIV infection. Established in 2002, the Consortium has grown from four academic institutions to 18.

In its AIDS Vaccine BluePrint 2008: A Challenge to the Field, A Road Map for Progress, IAVI says to accelerate the development and testing of a viable vaccine, several things need to happen.

Companies working in this research field needs to be given incentives as a way of enhancing innovation in Aids vaccine discovery and development as well as sustaining and enhancing funding towards vaccine research.

There is need to trim the product development pipeline of less promising vaccines candidates and those with low probability of success, with the resources being redirected towards more promising approaches or in solving key scientific challenges, according to the Blue Print.