The Kenya Aids Vaccine that was using a similar concept as the failed Merck and Company vaccine ha s finally been suspended permanently, leaving the scientists involved to work on new strategy of moving forward.

Although the Kenya AIDS Vaccine Initiative (KAVI) researchers had registered major successes in the phase one trial of their vaccine, they say they cannot proceed to Phase II using a concept that might not work.

The Kenya Aids Vaccine that was using a similar concept as the failed Merck and Company vaccine ha s finally been suspended permanently, leaving the scientists involved to work on new strategy of moving forward. 

Although the Kenya AIDS Vaccine Initiative (KAVI) researchers had registered major successes in the phase one trial of their vaccine, they say they cannot proceed to Phase II using a concept that might not work. 

A similar sad story of interrupted progress and failures is haunting scientists involved in the development of anti-HIV microbicides and those working on drugs for HIV treatment, where distressing resistance rates are being registered. By early this year, trials on five microbicides candidates had been halted. 

In the Merck and Company vaccine, which failed to prevent HIV infection or delay progress to AIDS, the recombinant adenovirus serotype 5 (rAd5) was the main component of the vaccine construct. 

The rAd5 was being used by the Kenya Aids Vaccine Initiative (KAVI) as a booster, in a vaccine designed to elicit Cellular Immune Responses against HIV/AIDS. 

But KAVI and International Aids Vaccine Initiative (IAVI) scientists say Kenyans should not lose hope since they believe the modified vaccine they are working on is likely to produce better results. The testing of this vaccine will start after ethical approval from the government and relevant authorities. 

“Although IAVI and KAVI team have finally decided to take this painful decision, there is still light at the end of the tunnel in terms of getting an effective vaccine,” says Prof Omu Anzala, the KAVI Director, in an exclusive interview . 

Other scientists in the vaccine world are putting on a brave face, describing the current failures as part of the agonizing process they have to undergo before finding a vaccine that works.

“I think by managing to move the vaccine trials this far and establishing a world class infrastructure for vaccine testing in Kenya, is an indication that we are making some progress in our vaccine work,” says Prof Anzala. 

Hopes are high that this KAVI and other vaccines designed differently from the Merck vaccine might produce better results. While the Merck vaccine used one vaccine constructed based on the rAd5, the KAVI vaccine used two vaccines- the DNA Vaccine as priming agent and rAd5 as a booster. 

Results of phase one of the KAVI vaccine trials showed majority of the volunteers to have elicited immune responses that were above the cut-of point of 55 Elispot forming units per a million cells. Hence, the Kenyan scientists believe by reconstructing the rAd5 arm, which was the source the problem in the Merck vaccine, then they might make headway on the matter. 

At the moment, over 30 Aids vaccines, which are under different stages of trial are designed to elicit Cellular Immune Response like the Merck and Company one. Although an AIDS vaccine that educe neutralizing anti-bodies like the measles and polio vaccines, is considered more potent, scientists have been unable to decipher just how to do it. 

Nevertheless, what is keeping the hopes of many AIDS vaccine scientists alive are the new observations on how certain individuals are able to control the virus without using drugs. There are high expectations that research around these areas is likely to lead to the development of an effective vaccine soon. 

Indeed, in the coming years, research is going to shift from focusing only on Cellular Immune Response -which is proving very difficult for the scientific community-to other areas showing startling developments. 

One of this are the HIV positive people, who scientists call Elite Controllers of the virus. In this category are people who are not on any medication, but have a CD4 count of over 500 and undetectable viral load. 

This means they are infected but are not developing AIDS, leaving researchers convinced that their immune system is eliciting either Cytotoxic T cells (CTL) capable of destroying infected cells and/or have broadly neutralizing antibodies. This new information is going to help improve the existing vaccines or form the basis of developing new ones, they say. 

Locally, KAVI is partnering with IAVI in a new project focusing on HIV positive people who are not on any medication, but have CD4 count of 350 above and are able to control their viral load at low levels. Majority of the people with HIV and not on medication usually have a CD4 count of below 200. 

Another area likely to boost efforts of finding an effective vaccine is information coming from discordant couples, where despite an HIV positive partner having unprotected sex with the negative partner, the latter remains uninfected. 

Scientists are burning the midnight oil to understand what makes the uninfected partner tick, and if the information can be used to develop an AIDS vaccine. 

The third area receiving a lot of attention in the last three months is the possibility of using live attenuated AIDS vaccines in human beings the way is done with measles and polio vaccines. 

While results of such AIDS vaccines in non-human primates have shown tremendous success, the scientific community is hesitant to test them in human beings for safety purposes. 

One of the reasons is unlike measles and polio in which majority of the people recover if the live attenuated vaccines results in an infection, the case is not the same with AIDS. The disease has no cure as yet. 

The Merck vaccine that has thrown a spin in vaccine trials involved 3,000 HIV negative volunteers, who were at higher risk of HIV infection. 

Recruitment of volunteers began in 2004 in nine sites-Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States. 

Known as the STEP trial, the vaccine had moved to the critical Phase II stage of “prove-of-concept” or a test that would have established the vaccine’s ability to prevent HIV infection or reduce viral load. 

The vaccine, MRKAd5 trivalent vaccine, was designed to stimulate the production of the immune system’s T-cells that are able to kill HIV infected cells.  The researchers were also keen to find out if the vaccine would reduce the amount of the virus in the body in people already infected or those who become infected. 

It never happened. The vaccine failed to achieve the two key objectives: prevent HIV infection or reduce viral load. Also troubling was, 13 months into the trials, 24 of the 741 volunteers who received at least one dose of the vaccine were infected with HIV. Another 21 of the 762 volunteers in the placebo group getting infected as well. 

Of those who received at least two doses of the vaccine, 19 out of 672 volunteers were infected with 11 out of 691 in the placebo group being infected. Although the infections are said not be due to the vaccine but the volunteers lifestyles, researchers are still concerned. 

An independent Data Safety Monitoring Board for the STEP trial recommended “that vaccination be discontinued because the trial was not going to meet its efficacy endpoints.” 

It was later established that the volunteers who had higher amounts of what anti-Ad5 antibodies before being vaccinated had increased chances of HIV vaccine. Leaving scientists wondering if the high levels of anti-Ad5 antibodies would make people more vulnerable to HIV infection. 

As scientists grapple with developing an effective AIDS vaccine, their counterparts who are working on microbicides are not having it easy either; indicating that the virus might be getting smatter each passing day. Several microbicide candidates have been abandoned or stopped after they failed to elicit the responses required. 

One of this is the recent stoppage of trials on the Ushercell also known as Cellulose Sulphate. During the trials, the microbicide was found to increase the chances of HIV infection among women volunteers who were using it compared to those were not using it (the placebo group). 

Trials on this microbicide were being conducted by Conrad in Uganda, Benin, South Africa and India, while Family Health International (FHI) did similar trials in Nigeria. Of the 1,333 women who participated in the Conrad studies, 35 got infected with HIV. 

In the Nigerian study, 21 of the 1,644 women volunteers got infected. This numbers were too high than expected, forcing an independent Data Safety Monitoring Board to advice the termination of the studies and ordered a detailed investigation conducted to establish why women were getting infected. 

Researchers however suspected some of these women might have been sharing the gel or engaging in unprotected sexual encounters believing they were protected. 

A microbicide is a gel or cream inserted in the vagina or rectum to prevent the transmission of HIV and sexually transmitted diseases. Others also act as contraceptives by immobilizing or killing the sperms. 

In addition to the Cellulose Sulphate microbicide, trials on other microbidies have too been stopped prematurely. Among this are the Nonoxynol-9 or N9 and Savvy microbicide trials. 

The N9 was stopped after it was found to be ineffective in protecting women from HIV infections. It irritated the vaginal lining and caused lesions when used in higher doses; factors that facilitated HIV entry. 

In one of the studies, 15 percent of HIV negative female sex-workers who received the N-9 gel became infected with HIV compared to 10 percent of those who did not receive it during the study. 

Likewise, FHI studies on SAVVY microbicide in Ghana were stopped after a review of interim data indicated that the study was not likely to provide convincing evidence on the efficacy of the gel. 

Other two microbicides, Carraguard and MIRA, which were promising, returned disappointing results after going through the efficacy trials. 

Another difficulty for microbicide studies has been the high numbers of women volunteers who get pregnant while on trials. When this happens, the women are taken off the study to protect the foetus; but the action makes it difficult for researchers to move on or come up with conclusive results. 

And as if the AIDS vaccine and microbicide troubles are not enough, scientists are being forced to deal with the increasing number of people developing resistance to the antiretroviral drugs. 

What HIV experts now fear is the circulation of these resistance strains in the population at time when it costs 10 times more to manage a patient with such strains compared to a patient the normal one. 

For now, the HIV seems to be mutating at rate faster than what the scientists can handle and adopting different survival mechanisms that are leaving on total awe.