HIV research hits a dead end
By Arthur Okwemba (HORIZONS, The Daily Nation - Kenya) 24 April 2008: It is bad news all around as HIV defy all scientific efforts to create an effective vaccine or microbicide while managing to resist most antiretrovirals.
It is bad news all around as HIV defy all scientific efforts to create an effective vaccine or microbicide while managing to resist most antiretrovirals. Local researchers, like most others in the world, have stopped work on HIV vaccines after the failure of what was thought to be the most promising candidate - at least until they can come up with new science.
The Kenyan trials, and several others around the world, were based
on a similar concept as the failed candidate which was stopped late
last year by its sponsor, Merck & Co after some volunteers became
infected with HIV. The experiment, called STEP, began in December 2004
and had enrolled 3,000 volunteers in Australia, Brazil, Canada, the
Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United
States.
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 its management where distressing resistance
rates are being registered. By early this year, trials on five
microbicide candidates had been halted.
The Merck & Co., vaccine, which failed to prevent HIV infection or
delay progression to Aids was using a concept called, the recombinant
adenovirus serotype 5 (rAd5), same as the one being used by KAVI.
But refusing to give up, the Kenyan researchers have set their eyes on
another vaccine candidate which could go for trials as soon as the
necessary ethical protocols are worked out .
"Although we have finally taken the painful decision of discontinuing
the study, there are plans to have new candidates in future," says Prof
Omu Anzala, the KAVI director, in an interview with Horizons.
While the Merck candidate used one construct, KAVI's had two- possibly
explaining why the phase one trials had made a good showing.. At the
moment, over 30 HIV vaccines, which are under different stages of trial
are designed to work in a similar way with the one from Merck & Co.
Ideally, researchers would wish to develop a vaccine that works on the
same lines like the one for polio or measles but so far have not been
able to decipher just how to do it.
Nevertheless, what is keeping the hopes of many vaccine scientists
alive are 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.
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 (These "helper" cells initiate the
body's response to invading micro-organisms such as viruses) count of
over 500 and undetectable viral load.
This means they are infected but are not progressing to Aids, leaving
researchers convinced that their immune system is 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 International Aids Vaccine Initiative
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
a vaccine.
The third area receiving a lot of attention in the last three months is
the possibility of using live vaccines in human beings the way it has
been done with measles and polio.
While results of such HIV 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 HIV which has no cure.. The disease has
no cure as yet.
As scientists grapple with developing an effective HIV 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.
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 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 per cent of HIV negative female sex-workers
who received the N-9 gel became infected with HIV compared to 10 per
cent of those who did not receive it during the study.
Likewise, studies on another microbicide, SAVVY, 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 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 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. For now, the HIV seems to be mutating at
rate faster than what the scientists can handle and adopting different
survival mechanisms.

