TCE pilot study

In August 2000 the Foundation received an application from the Federation for Associations connected to the International HUMANA People to People Movement. The application asked for 200,000 Danish kroner to do research into and test the effects of already existing drugs on the HIV positive, in a trial for the purpose of proving that inexpensive medicines can advantageously be used by the majority of HIV positive in the world, who cannot afford the life prolonging triple anti-AIDS treatment.

HIV/AIDS - and Medicine for the Disease
HIV/AIDS was established as an epidemic only 20 years ago in the United States. During the subsequent years it spread to a number of other geographical locations - and during these years the World Health Organization and other experts in the field realized that the disease was not only an EPIDEMIC - a disease in a defined area - but a PANDEMIC - a worldwide disease.

Today there are few places in the world where this disease has NOT reached. It points society into a threatening direction in Africa, which is the place in the world most heavily affected by the disease. The same is true for the Caribbean, which holds a gloomy second place in this context. Furthermore, the prevalence is drastically increasing in India, in China and in South East Asian countries, as well as in Russia and eastern Europe. So far around 22 million people have died from AIDS, and 36 million are infected by the HIV.

The disease is caused by an unusually smart virus. A virus is not in itself alive, but spreads by invading and utilizing living cells, which it brings under its control and uses for its own benefit. The HIV virus is very deadly. It is practically transmitted only through sexual intercourse, direct blood contact, or vertically from pregnant mothers to their children. Once a person is infected with this virus, there seems to be no way around the consequences: The virus slowly but surely destroys one's immune system, and one dies. It does take a number of years - for example between ten and twenty years - to die from an HIV virus, depending on how good an immune system one has, how one treats it along the way, and a number of other conditions which can partly, but not in the end, be regulated.

In the US and in Europe the disease first appeared among homosexual men, whose environment came to act as a generator in the spread of the HIV virus. This beginning of HIV as a modern plague meant that for the first ten years, the virus and its subsequent weakening of the immune system and AIDS were understood as a phenomenon which exclusively hit homosexuals. This meant, that it was observed relatively late in Africa and Asia that the HIV virus spreads heterosexually, and that the dangerous virus therefore has much greater possibilities for spreading to a larger number of people. In these parts of the world, some of the generators for spreading HIV/AIDS have been war with a large number of soldiers, prostitution and a sex industry, populations on the run, smuggling and transport of goods - with a concentrated spread of the infection as a result, which thereafter is disseminated out into many homes in cities and country side.

Another delaying and outwitting factor of the HIV virus is that a long time passes while one is infected but not sick. And during this whole time one is able to infect others.

It is clear from the above, that in order to have a chance against the HIV virus, one has to know it, protect oneself from it - and if one is infected one has to take good care of oneself and ones immune system, so that one lives as long and as well as possible with HIV. This means, that with an informative effort with regard to the presence and workings of HIV, in reference to how it spreads, in reference to promoting the use of condoms which can prevent infection via intercourse, one can do a lot to avoid getting infected.

Only in the US and in Europe has the disease been brought under some kind of control. A public and health oriented effort has been made to map and to understand HIV, how the virus works and affects the immune system, and it has been researched into possible preventative and treating drugs, and into the production of a vaccine against HIV. Furthermore much work has been done to spread the knowledge about HIV/AIDS to people who are infected or in danger of becoming infected. This has been done by some of the world's most developed health systems, which have lots of resources, competent doctors and research institutions, and many other advantages.

A contributing factor of bringing the disease under control in the US and in Europe was the invention of an anti-HIV medicine in 1996, able to stop the HIV virus inside the human cell - the so-called triple combination therapy. This medicine has saved the lives of a number of HIV infected people in the last minute in these parts of the world. However, this achievement cannot at this moment be transferred to the developing countries in Africa, the Caribbean, and Asia, in that the therapy is so expensive that it cannot practically be used here: There is no one, neither individuals nor governments, who can pay for it!

Thus in relation to the world's 36 million HIV positive people there is a pressing need for:

• partly making the triple combination therapy cheaper, so that it can become accessible to the 95% of the world's HIV infected living in poor countries.
• partly researching into other possibilities, inexpensive therapies and approaches which can contribute to the delay of the virus's reproduction in the body, and which can contribute to the strengthening of the immune system under attack by HIV.

The first one - making the triple combination therapy cheaper - concerns big money and big interests. Many are involved in applying pressure to make this happen and to find each other so that solutions can be found: the UN, the pharmaceutical companies, governments, regional associations, development banks, and large donors. It has, however, been going on for some time; so far without many practical results for the people in the developing countries who are without any means to pay the price of today.

The last one - researching into other possibilities and inexpensive therapies and approaches - is the subject of the application we are concerned with in this chapter. The application received by the Foundation was called "A Pilot Study to Demonstrate that Affordable Therapies for HIV Exist."

About the Application
We here quote from the introduction of the account for the Pilot Project which was attached to the application:

"After almost twenty years of research, only two mechanisms of action are commonly used to treat HIV disease, reverse transcriptase inhibitors and protease inhibitors ('reverse transcriptase' is the process where the virus takes over the control of the cell, and 'protease' is the process which supplies the new virus particles with a protein coat which secures that it can survive). Because of the expense of these drugs, less than 10% of the people worldwide with HIV receive effective anti-retroviral combination treatment. At most, only 5% receive highly active anti-retroviral therapy (HAART), the standard of care in the US and Western Europe.

For the last decade, scientists in Europe and the United States have suggested that HIV may be inhibited by targeting mechanisms other than reverse transcriptase and protease. Several immunologic mechanisms have been suggested, including inhibition of transcription factor nuclear factor kappa binding (NF-kB) and the cytokine interleukin-6 (IL-6).

A number of laboratory studies and small clinical trials have been conducted which have demonstrated the partial effectiveness of a number of common, inexpensive drugs working via these mechanisms in inhibiting HIV replication. Drugs which have shown an ability to inhibit HIV by targeting these various mechanisms include, but are not limited to aspirin, chloroquine and the mineral supplement selenium.

This three arm randomized clinical trial is designed to test and compare the anti-retroviral effects of these drugs in two different combinations.

The purpose of this clinical trial is to determine the best possible affordable anti-retroviral combination therapies for application in developing countries and to improve HIV combination therapy in the developed world."

Thereafter the trial is thoroughly described.

It will be carried out in the context of Humana People to People's TCE programs in Zimbabwe, in the TCE Areas of Bindura and Shamva, in a rural area around the provincial capital of Bindura, and hour north of the country's capital Harare.

The directors of the research is the immunologist Dr. E. N. Sibanda, Harare. The trial will be delivered for approval by the Zimbabwean government's authority for such trials, the MTCZ.

The idea is to test two different combinations of HIV inhibiting substances, as well as a placebo (a drug without any active ingredients) on three different groups, such that none of the people in the three groups know which medicine/placebo they receive.

The plan is that the trial will last for six months, and involve thirty six people.

• Group 1 of twelve people will receive SAM - selenium, aspirin and multivitamin.
• Group 2 of twelve people will receive MACS - multivitamin, aspirin, chloroquine and selenium.
• Group 3 of twelve people will receive a placebo - which looks like the other tablets but does not contain any active ingredient.

The participants will be tested for their CD-4 count and viral load at the beginning of the trial, half way through the trial, and after the full six months. Thereafter the trial results will be examined.

How is the Trial Going?
In May 2001 the Foundation's board of directors received a progress report about how the trail was started - with the promise of a final report in August where the results from the trial are compiled, evaluated and concluded on, and possible consequences are included.

Here is a short chronological account of how the trial was started:

October 11 - December 04, 2000: The Recruitment Period
The daily leadership of the trial, doctor Marianne Thomsen and assistant Anne Marie Sørensen and ten TCE Field Officers from the Shamva and Bindura areas recruit and inform 55 people about the trial, take CD-4 and viral load tests, as well as other blood tests. 33 people were recruited for the trial. 22 people had CD-4 counts which were too low and they were instead taken into a treatment group running parallel to the trial group.

December 05, 2000
The first 33 trial participants started their tablet program, divided into the three groups. All groups received the same amount of tablets. No one knew what they received, and neither did the doctors and other personnel. All drugs and placebo were donated by two Zimbabwean medicine producers: CAPS Holding and Varichem.

December 12, 2000:
Checkup of all groups with regard to everybody taking the medicine as planned, and with regard to any possible side effects.

January 19, 2001:
One more checkup of everybody with regard to general health condition and side effects.

February 26, 2001:
Midway checkup with blood tests.

At the present moment, the following may be considered results of the project, although it is not completed:

• All participants have kept taking the drugs - no one has dropped out of the trial.
• Generally the participants feel they have benefited a lot from the project, which, apart from its concrete contribution of drugs, has provided important general information about HIV/AIDS to all the participants, and has resulted in a clear focus on each participant's condition of health. This has also meant a much greater awareness of how the participants themselves can do something about their infection and the pathological picture. Furthermore, there is a valuable social network created around the HIV positive participants, mainly in their relationship to the TCE Field Officer where they live, but also in relation to the TCE doctor and nurse.
• Every month TCE has visited the participants in both the trial and the treatment groups and distributed food donated to TCE by the Latter-day Saint Church in Harare, Zimbabwe. This was done because it became evident from the start that poor and insufficient nutrition, or downright starvation, was a considerable problem for the participants in both groups, and this would compromise the results of the trial if nothing extraordinary was done.
• The mid way tests of the viral load with regard to MACS showed a very positive result for one of the participants, and considerable improvements for the average of the rest. Improvements could also be identified with regard to SAM.

TCE and the leadership of the trial did not expect any significant results after three months, but meant that a minimum of 4-6 six months would be necessary to show any such results. Therefore the trial was set to last for six months.

The last blood tests will be taken on June 5, 2001. They will be analyzed and treated, and when the results are present, an actual statistical analysis will be carried out. After two months - in the middle of August 2001 - the project expects to forward a written final report to the Foundation's board of directors.

The Use of the Money
The amount of 200,000 Dkr applied for to this trial was based on the research director, the doctors, and most of the personnel participating on a volunteer basis, and furthermore that that the TCE as a program recruited the participants, and themselves took part in the practical, informative, and logistical questions.

The budget made in connection with the original thirty six trial participants was as follows:

In the original application the plan was to enroll 36 people who were in the early stages of HIV infection. In reality 33 people were enrolled, whereof the majority were in the early stages.

At the same time there was a group of 22 people who, as mentioned earlier, were treated when their results showed a more advanced HIV infection, and who therefore did not qualify as participants in the trial according to the research protocol.

The trial secured a donation of drugs to treat also the 22 people in this group, since the research director and the personnel did not find it ethically justified to simply send them home again. In order for the economy to anyway cater to 55 instead of 36 individuals, certain extra efforts were made: As already mentioned, food was acquired without a cost in order to generally improve the trial and allow for more accurate results. In addition, the blood tests were negotiated and reached a favorable price, so that also the 22 people could be tested. In this way creating both a trial group and a treatment group was turned into an advantage for all.

The transportation turned out to be a problem, and the actual expenses exceeded the original budget. The majority of the participants are from the rural areas - far from Bindura town, where people come for checkups and distribution of new medicine.

All in all the project has, according to its May 2001 report, used approximately 2/3 of the budget, and has sufficient funds to carry out the remaining activities.

A Look a Little Further Ahead ...
Before long it will show if the medicines which were tested in this trial are able to make a difference in the fight against HIV/AIDS. If this is the case, then we are talking about an important advance since the ingredients in both combinations tested, SAM and MACS, are cheap and therefore possible to spread widely to many people in Africa.

The Foundation's former board of directors looks forward to the result with great expectation, but will under no circumstances regret its decision to support this project should the desired result not be proven in the final analysis in a few months.

The former board of directors and the contributors of the Foundation are pleased to have been a part of effectuating a test of these conditions - for very little money, in a disregarded place in the world, with respect to a disease where even the smallest result can have huge effects because of the magnitude of the problem in Africa. And it encourages many, similar trials to be carried out in the future. For now is not the time to save on any effort in relation to HIV/AIDS!

The Foundation for the Support of Humanitarian Purposes, for Promotion
of Research and for Protection of the Natural Environment
More on: http://www.fonden.org/