Ellen 't Hoen: Thank you Kris, and welcome all to today's call. I will give a very brief introduction outlining our concerns, which are mainly related to the meeting that will take place next week on March 29 and 30th in Gaborone, Botswana. There will be a conference on fixed-dose combination drug products. Fixed-dose combinations are drug combinations that are often taken as single doses in one pill. The reason why these three-in-one pills -- for example in the case of AIDS treatment -- are very important is because it really helps in increasing the number of people who can be put on treatment. There are tremendous advantages from a medical point of view in the use of these types of medications. I will stick particularly with my example of HIV/AIDS, because I think that is the best way to illustrate what is going on at the moment.

Several reasons why we like to use this type of medication wherever possible are because first of all, it really changes the lives of our patients. It helps with the appearance that it is easier to take. If patients are more likely to take their medication, you decrease the risk of the development of resistance. In general, it helps ease the management of a project. For example, the drug purchase, the supply and distribution of medicines, is much easier when you deal with one or two fixed-dose combinations then if you have to stock all the single components of the treatment and provide all the single components of the treatment to the patients. Also in the case of HIV/AIDS medicines, the fixed-dose combinations or so-called three-in-one pills are, at the moment, the most affordable versions. Now there is an international consensus on this and, in fact, anyone who applies a bit of common sense would say, yes, of course, if I have a choice between taking six pills twice a day or one pill twice a day, why would I choose taking six pills a day, right? So that's the common sense, but particularly for the medical arguments, we're very heavy on the side of the fixed dose combinations.

In December, there was a large meeting on fixed-dose combinations organized by the World Health Organization where the consensus was very clear that the fixed-dose combinations remained the first choice when they are available. So the question then is, why is there so much debate over these fixed-dose combinations versus the use of the single components of the treatment? One of the important reasons is that those fixed-dose combination medications which we are using now are developed and produced mainly by companies in developing countries by the so-called generic producers. The first line recommended fixed-dose combinations are not produced or provided by the European or US-based companies. The reason for that is fairly simple: these are the different components and the intellectual property of the different components of those medications are held by different companies or by different package holders, so they have intellectual property barriers to putting the drugs together. Where those barriers do not exist, companies do produce the fixed-dose combination. A company such as GlaxoSmithKline, for example, holds the rights to several of the components and has been able to produce a double fixed-dose combination and a triple fixed-dose combination, although the triple fixed-dose combinations are not part of the recommended first-line treatment.

Of course, we share the concern of everybody who expresses the need to assure quality. The drugs, of course, need to be effective, need to be safe, and need to be of quality. There is another very strong international consensus on that particular pool. That is why it is very important to look at the role of the World Health Organization in this. The WHO (the World Health Organization) started a project a couple of years ago, which is often referred to as the pre-qualification project. And what it does is look at the dossiers of the medicines. Companies can apply for WHO pre-qualification, and the WHO will go to the companies, visit the companies, look at the dossiers, and assure that those drugs that are submitted for the WHO pre-qualification are indeed of the same quality as the originator drugs. A number of the fixed-dose combinations produced by the generic companies in the developing country that have been pre-qualified by the WHO are also the products that we use. The WHO pre-qualification process is an ongoing process, a different case than if the WHO just gives a stamp. It regularly revisits the dossier and also regularly visits the companies where those drugs are produced.

So why do we worry about the Botswana meeting, because isn't it good that more people talk about these fixed-dose combinations? We believe that would be good if that indeed was done from the basis of support. But we hear from one of the initiators of this conference a very clear signal that the US government is not prepared to support the use and procurement of generic medicines or the fixed-dose combinations produced by generic producers with, for example, the funding the US government plans to provide for AIDS treatment. And we are very worried that these arguments of quality and safety of the medicines and the constant questioning of quality and of the safety of the medicines, where it is not appropriate to do, will lead to the loss of confidence in these products. It's actually mainly used as a smokescreen to stop the procurement and use of these drugs. We have quite a bit of information on those drugs and others will talk about that. We have, at the moment, 11,000 people on antiretroviral treatment, of which 50 percent are on fixed-dose combinations, and you can imagine that we are following this development with a lot of concern.

Kris Torgeson: Thank you Ellen. We will move next to Dr. Saleban from Homa Bay in Kenya.

Dr.Omar Saleban: Thank you Kris, and good morning and good evening ladies and gentlemen. I am working for MSF in the Homa Bay HIV and Antiretroviral Project, and I would like to share with you some of our field experience. In November 2001, Médecins Sans Frontières started this ARV therapy program in Homa Bay District Hospital in the Nyanza province in Kenya. HIV prevalence estimated in this region was between 30 and 35 percent among the sexually active age group. Our first-line treatment is fixed-dose combinations generics. Currently, more than 1,100 patients are receiving antiretroviral therapy in the Homa Bay project and almost 800 of these patients are on fixed-dose combinations of antiretroviral drugs. Triple fixed-dose combinations have clear advantages for Médecins Sans Frontières and the other institutions or agencies, such as ease of use -- patients need to take only one tablet twice a day. This helps adherence and leads to better clinical results. For example, in the Homa Bay project, we are happy to report that our adherence rate of those patients on fixed-dose combinations is 97 percent. The mean increase of body weight is three kilograms since the initiation of the antiretroviral therapy project. Also, the mean increase in CD-4 tests after six months and after 12 months of antiretroviral therapy is 125 and 148 respectively. CD-4, to explain a bit more, is a measure of the defense cells that resist against infections. Only five patients on fixed-dose combinations of antiretroviral therapy have been hospitalized since the beginning of the project.

In addition, I would like to also talk about the side-effects that we have observed in our patients. Only 30 patients out of 1170 have stopped stavudine due to side-effects. And less than one percent of the patients have had liver toxicity due to nevirapine. However, permanent side-effects of nevirapine in our programs is a skin reaction which accounts for almost two percent of nevirapine side-effects.

For Médecins Sans Frontières, fixed-dose combinations have enabled us to scale up our ARV programs due to interviews, for example from good adherence to minimum side-effects and low costs. From November 2001 to April 2003, we have been able to treat 400 patients with fixed-dose combinations at an approximate cost of US $350 per patient per year. The introduction of triple fixed-dose combinations in our program in April 2003 facilitated the treatment of more than 1,300 patient at costs of US $270 per patient per year. Several reductions in generic antiretroviral costs will enable the treatment of even greater than double the number of patients. Last but not least, contrary to US claims, our clinical observations demonstrate that patient receiving fixed-dose combination generics have parallel if not improved clinical outcomes. Generics and fixed-dose combination antiretroviral drugs enable us to treat at least twice as many clients in a cost-effective, safe manner. Bear in mind that millions of people are unable to access this antiretroviral treatment in Africa today. In meeting MSF humanitarian goals of providing access to health and essential medicines for the greatest number of people, fixed-dose combinations are our fundamental tool. Thank you Kris.

Kris Torgeson: Thank you so much Dr. Saleban. Dr. Eric Goemaere from South Africa will speak next.

Dr. Goemaere: Good evening everybody. I'm calling from Khayelitsha in South Africa, one of the treatment sites of MSF. To wrap up what the previous speakers have said on why are we so upset with fixed-dose combinationÉ I think everybody knows that South Africa is a good example. The key motivation nowadays is scaling up. We will soon see the end of the era for the pilot project where they are treating a few hundreds of people. We will soon be speaking of thousands of people. And as a matter of fact, the South African government has launched a program that might be that great -- the biggest program in the world, treating between half-a-million and one million people. You cannot scale up if you don't simplify. You need to simplify wherever possible because you need to multiply your treatment size by hundreds. Every single clinic in this country at the end of the day will be able to deal with those prices.

It appears more and more in South Africa to be the case that the main constraint is staff. No single country in Africa, and certainly not South Africa, has the amount of doctors to manage this. So we are pushed into a situation where we will be forced to use nurses to deliver treatment, nurses based in the most remote areas. As a matter of fact we have started two treatment sites in South Africa, here in Khayelitsha and another one in one of the most rural remote areas of South Africa. For those places, there is no alternative because there is no doctor over there except the one we temporarily provide. There is no alternative in terms of sustainability other than to use nurses in remote distant clinics. And for them, as well as for the patients, the only possibility for antiretroviral treatment is a triple therapy. They need to understand that antiretroviral therapy is about taking one pill a day in the morning and one day in the evening. That's all they can understand. There is no way we can go into the pharmacology of each of the different drugs. It's not their problem, it's our problem. And only if we can solve these problems technically with all the constraints that we know in technical terms then will they be able to be adhere. So fixed-dose combinations are the key to success for the kind of program we are speaking about, if we don't have them we will never be able to reach our goal. Although they are not all recognized by the MCP, the local regulatory authority, we have some double combinations, we are still eager to use the triple combinations, like Dr. Saleban in Kenya, because they have been registered to it. As a matter of fact we ask for special exemption, at least in our rural sites, to be able to use them because we believe that, that's the only way. But we need much more than what exists, we need two lines of treatment and to be able to cover the one with TB co-infection. When it comes to children it's a literal nightmare. A typical example is child who would be sick and the triple therapy where you have to advise and teach usually the grandmother because the mother passed away.

How can you tell the grandmother that she needs to give -- for example a very specific dosage of nevirapine, a very specific amount of another drug and do exactly we ask with them? She now has three different syrups in three different bottles with three different labels and she is supposed play the nurse and administer three different amounts from each. Fixed combinations would definitely percent easier and it allow us to extend treatment to rural areas as well. So just to finish and put it in the South African perspective, we have always pushed to have the capacity of local projection in South Africa because, we believe strongly that there is no one country in the world that could seriously look at treatment of between 500,000 and one million people when buying those drugs abroad and paying in foreign currency. So local projection is the key. We know that the local producers have the pipelines, the fixed combination. We are concerned that local projection efforts might dramatically be swept away, and potentially even killed by the new message we are hearing. And this would probably mean the end of the national treatment program in South Africa. Thank you.

Kris Torgeson: Thank you Eric. Okay. We will close the opening remarks now with Sharonann Lynch from Health GAP and after that we will take questions and answers.

Sharonann Lynch: Thank you, Kris. Hello everyone, my name is Sharonann Lynch. I am the Director of International Policy for the US-based NGO Health GAP. I think certainly the most urgent question is: is Bush's priority getting medicines of assured quality to poor Africans dying with untreated AIDS? And the answer is, clearly not. Bush's priority right now is to ensure dominance for big pharma, and not for countries scaling up treatment access. As you have heard from our colleagues on the phone, despite international support for the standards by the WHO on quality AIDS drugs, the Bush administration intends to block countries from using US money to buy the fixed-dose generic medicines. Although these drugs are quality assured and at least four to five times cheaper than the brand name products, if the administration is successful, desperately needed money would be wasted on over expensively priced products, and fewer people would get the treatments they need to live. In addition to wasting money, through the tremendous efforts of administration to discredit WHO projects and to discredit the use of generic FDCs (fixed-dose combinations), we will waste time. We already had a 13 month delay from the time the Bush administration first announced the goal of putting two million people on treatment by 2008, to just last month when, finally, the five year strategy plan was delivered.

Now more time will be wasted in setting up -- expanded parallel burdens from regulatory agencies or (indiscernible) Federal Drug Authorities if you will. This is about wasting money, wasting time and wasting lives. I agree wholly with Ellen, who said that Bush is using quality here as the smokescreen. Now the President's Emergency Plan for AIDS Relief officials recently suggested that AIDS activists should be jumping up and down, celebrating the great shift in policy where the administration is willing to consider generics. However, we see that the only shift that has occurred here is that the US is going from an unapologetic stand to using quality as a smokescreen, thereby maintaining the monopoly of branding companies and the consequences be damned. So this is business as usual, and this is industry protection and politics masquerading as science. Looking at Bush policies within the context of US politics, we see the administration protecting these policies as one of the most important issues of the presidential campaign, which is why Health GAP is comparing candidates' positions on global AIDS and also their positions on the use of affordable generic medicines. So within the current political context this election year, the Bush administration is using similar concerns of quality against re-importation of medicines from Canada. The cost of health care is booming here in the US and voters will soon realize the US government has tied up its own hand, unable, because of the Medicare legislations, to negotiate with big pharma for lower prices of medicine. Now the Bush administration talks of plans to block the use of generics in their global AIDS programs. This provides ample fodder for this to be a critical issue between the candidates and all of this will play out in the campaign trail. There is now more evidence because of the Botswana meeting and because of the larger context against the onslaught of these generics of the unilateralist Bush. He is rejecting internationally recognized WHO standards on present drugs. We will certainly hear accusations of 'industry puppet Bush." The Bush administration is ensuring the monopoly for favorite companies through this AIDS plan or has -- as some have already been referring to it -- the big pharma slush fund. Tax payers will say to Bush and have been saying to Bush, rather than squandering tax payer money to please the big pharmaceutical companies, keep four times the number of people alive with the same amount of money. As you have heard, many programs in resource poor settings in Kenya and some of the other recipient countries are procuring fixed-dose combinations of generic medicines with positive effects. And as hard as Tommy Thompson tried, branding companies are refusing to come together and formulate powerful combinations together in one pill. By disregarding the existing generic FDCs that are WHO-recommended for first-line treatment and using the weak and hypocritical arguments about quality, the White House is showing yet again the scientific facts are just disregarded when they don't advance the political goals of the administration.

Another name that we will hear on the campaign trail, is 'the global bully Bush." Again, President Bush is undermining international institutions by under-funding the Global Fund to Fight AIDS, TB and Malaria; by discrediting the WHO's pre-qualification projects; and by chipping away at national governments' sovereignty and their ability to shape their own procurement policies with the technical guidance provided by WHO. I think people have already mentioned this, but it's important to reinforce the fact that if parallel systems are created, this will cause new problems in poor countries that are confronting the AIDS crisis. Because instead of reinforcing the efforts of national AIDS programs -- most of which endorse WHO's HIV medicines and rely upon WHO technical guidance -- Bush's nonsense policies will create an entirely parallel system of project implementation that will waste time, may waste money and will undermine national standard setting efforts. Because while African ministers of health are trying to implement new national AIDS treatment plans that include in some cases generic procurement, the US will implement drug plans in the same places that contradict and therefore even undermine the efforts of national governments. Multiple, complicated, competing systems in the same place will create confusion, chaos, and stretch even thinner already overburdened and fragile health care systems. On the campaign trail we will hear Bush's lies. The US-initiated meeting in Botswana is politics masquerading as science. And again it's clear that the White House is willing and able to go to any length to misrepresent science and use the claims of quality in order to achieve its political gain. Unfortunately, in this case it will cost the lives of the very people Bush claims he wants to help. I would like to announce that Health GAP plans on submitting an analysis of Bush and Kerry's plans and their positions on the procurement of generic medicines. It includes responses from the Canada to a questionnaire that Health GAP devised and its early indication. It's clear that while Bush's position will scandalously waste money on overpriced medicines, resulting in fewer people treated and a schizophrenic lack of program co-ordination in an already over burdened clinical care setting, Senator Kerry pledges to 'adopt a policy consistent with international trade rules that purchases lower cost, quality medicines including those presented in fixed-dose combinations whether brand name or generic through transparent open competitive business." He also writes, 'as president I intend to ensure that all relevant agreements negotiated under my tenure will increase access by developing countries to generic affordable drugs." Thank you very much.

Kris Torgeson: Thank you Sharonann. Now we will take some questions.

Barbara Borst: Hello, this Barbara Borst from AP, my question is to Ellen 't Hoen first. I have been in touch with US officials on this subject, and they say that they are not using the issue as a smokescreen, etc, etc. So what I'm looking for is -- you mentioned signs from the US government that this issue of safety is going to be misused. And I wonder if you could be more specific about some of the signs that you see. And the second question (I'm not sure if it should go to Ellen or to the two people in Africa) is, what are your means for determining the effectiveness of the combination drugs you are using in the field? Are you able to do some of the same kind of testing that would be done in the US? I'm not a doctor, but whether it's blood testing or whatever else, you need to be sure that these drugs are being effective. Are you able to produce those kinds of clinical verifications of how effective they are?

Ellen 't Hoen: The best source to look at US government policy on this question is to examine the US government themselves. There have been a number of statements in the last few weeks, for example, from Ambassador Tobias, the head of PEPFAR, about the medicines we are talking about. For example I have quotes from my hearing before the House committee and we can get those quotes to you, I believe after the call if you would like. But statements like this, 'We have been reading stories lately about some problems with some drugs around the world where people with the best of intentions have made acquisitions of drugs that have turned out to not have the consistency and the safety and the effectiveness that people had hoped." Another quote: 'unfortunately when people today say we ought to buy generic, they are not describing, in many cases, what we imagine when we think about generic drugs here in the United States."

Another important source are the requirements for grantees of US money where the US government requires that the pharmaceuticals procured with their money are approved by the US Food and Drug Administration. Now we know that the US Food and Drug Administration has not and cannot approve dossiers of the fixed-dose combinations. The companies will not apply for the approval because the companies cannot market them in the US for patent reasons. There might be medical reasons why people in US would like to use them -- I could imagine there are also US-based patients who would like to use fixed-dose combinations -- but for those reasons I just mentioned, those drugs are not available. Should a grantee wish to use other drugs, they have to submit a waiver in which they cannot rely on the WHO pre-qualification. And I think that the Bush administration's complete rejection of WHO's work on pre-qualification assuring the quality of these medicines is the most important and the most serious signal and evidence of their attitude towards these drugs. As I said earlier, we share the concern that these drugs need to be effective and that they need to be of quality, but that is why everybody who shares such concern should also share the view that the WHO, which is the single most important institution that can do this, needs to be supported and strengthened in this work and not further weakened.

Kris Torgeson: Dr. Saleban would you like to respond to the second part of that question?

Dr. Omar Saleban: The question on our clinical efficacies are based on our clinical divisions, and every day we see hundreds of patients in our clinics. For example, in Homa Bay Treatment Center, when they start antiretroviral therapy, more than 70 percent of our patients have defining illness, and after three months to six months they are stable, which means they don't have opportunistic diseases and they are back to life and resume their jobs. I mentioned it previously in my talk that we have observed a dramatic reduction in the number of hospitalizations after the patients start antiretroviral treatment. I also mentioned the increase in the number of defense cells after the patient starts antiretroviral drugs. In addition to that, I mentioned the rate of adherence because of the simplicity of using this fixed-dose combination. Of course, maybe there is a need to compare the other studies and experience in the developed countries, but what you are talking about, we, our clinical division, see everyday in front of us. Thank you.

Joe Decapua: Thanks, Joe Decapua, Voice Of America. I spoke with the office of the US AIDS global coordinator this morning and just some preliminary commentsÉ One person was quoted as saying they have no predisposition not to buy generics, but they are concerned that these generics have no FDA approval, that they are looking for an international consensus on these drugs and that MSF, while it uses the drugs, it uses them on a much smaller scale than the US plants do. The US says it hopes to treat millions of people whereas MSF currently treats thousands, and perhaps we are not getting an accurate reading on the safety of the drugs. Possibly Ellen and maybe Sharonann may comment on this.

Kris Torgeson: Ellen, go ahead?

Ellen 't Hoen: Yes, with pleasure. There is an international consensus on these medicines and there is an international institution that has the mandate to look at the quality and help countries, and help national regulatory agencies to deal with these questions, and that is the WHO pre-qualification. In the WHO pre-qualification project, it might be interesting to know, there is a collaboration of a number of national drug regulators including those from Canada, from the UK, from Australia and a number of other countries. Repeatedly, the WHO has asked the Food and Drug Administration to be part of the process and the FDA has not been able to respond positively to that request. So if the people you were talking to are serious, then there are a number of things they can do: they can acknowledge and help strengthen the WHO system; they can take note of the international consensus that exists; and they can allow the FDA technical people to participate in the process.

Kris Torgeson: Eric did you want to add anything about the question of the number of patients that MSF has on antiretroviral now?

Dr. Eric Goemaere: Well, as mentioned, MSF has 11,000 people already on antiretrovirals. We hope to expand the treatment to 25,000 people by the end of the 2004. If there was good faith, I think it would start by studying the results we have with those people using FDCs instead of putting everybody back to square one by saying we need to re-discuss the quality requirements. There is a empirical method and a possibility to use that method. We have made all the data available to them, but they have not been able to analyze it.

Kris Torgeson: Thank you. Sharonann do you want to follow-up on that question?

Sharonann Lynch: Yes, I would. A couple of comments. One, the US does say that they hope to reach an international consensus but really what they are seeking is a rubber-stamp of principles that have already been drafted and of a policy that's already been shaped. There already has been international consensus. There was a meeting in Geneva where it was basically decided upon that these fixed-dose combination drugs are critical if WHO's goal of three million people on antiretrovirals by 2005 will be reached. And that's a larger goal than what the US is thinking. I think it's also important to point out that the US is being hypocritical on its stand because right now the FDA doesn't currently require manufactures of brand name, fixed-dose combination medicines the kind of clinical data they are suggesting generic companies must now provide. We had a case here in the US, where GlaxoSmithKline, the manufacturer of fixed-dose combination Trizivir (a brand named product that it's not strong enough to be used on its own) got US approval without doing the special clinical trials of its drug. It just did studies to establish formal equivalency which is something that WHO already requires the drug companies to do.

Operator: Our next question comes from Christy Feig of CNN. Your question please?

Christy Feig: I think we are all kind of going after the same thing here. I understand the anecdotal evidence, I guess I'm wondering if anyone can give us some specific details about the science behind the WHO pre-qualification? I mean has somebody actually sat down and tested these fixed-dose combinations for 48 weeks up against a brand proving that they are both suppressing in the same way? Anyone know about that?

Kris Torgeson: Who would like to address that question?

Ellen 't Hoen: I can address that. We should be clear about the pre-qualification and how regulatory decisions are made. Sharonann just referred to the GlaxoSmithKline (indiscernible) European medicines evaluations agency also approved the use of the fixed-dose combination by comparing the bioequivalency of the fixed-dose combination with the bioequivalency of the single component drugs. That is the international standard, that is also how the FDA would do it, that is how the WHO looks at it. It's not that the WHO has made up new standards to look at the quality of these drugs. Then in addition to that there is of course growing clinical information because of the large number of patients on these drugs. We are treating about 5,000 people with fixed-dose combinations and we have very good results with those drugs. There are smaller trials being carried out that confirm that these drugs are of the right quality and that they have, clinically, exactly the kind of effect you would expect the single dosage to have.

Christy Feig: So those trials are underway basically right now?

Ellen 't Hoen: There are trials being completed and some of those results will be presented later this year at the Bangkok conference. We have been in a position to share the preliminary information with the people in the Bush administration, including with the scientist at NIH who acknowledged that this was encouraging data.

Christy Feig: Okay, (pardon my ignorance) if I can ask a follow-up on one thing, bioequivalency -- how is that tested?

Ellen 't Hoen: That is tested in humans. You have to do the clinical tests with patients and look at whether the drug you are testing has the same bioequivalency. You compare that with the single dosage, for example.

Christy Feig: Great, and for the one that you are talking about in Europe -- how many weeks did that trial last?

Ellen 't Hoen: I do not know, I imagine that might be different. I am not a pharmacist nor a regulatory expert. But I could get that information to you.

Operator: Our next question is a follow-up question from Barbara Borst of Associated Press.

Barbara Borst: Hi, thanks, I do have a couple of follow-ups. I want to be sure that I understand correctly, Dr. Saleban -- the clinical observations that you spoke about, in contrast with actually doing the blood tests and the other chemical tests, that's not something that you were able to do in that setting. So you are talking about clinical observations rather than in fact doing the chemistry of testing the effectiveness. So that's one question and another, I would like to know, Ellen, about the requirements to use FDA approved drugs. Can you tell me where to get out that information so that I can see what the requirements are for those seeking grants from the US government? And finally, just to raise one of the issues that the US government people raise repeatedly. If you put this money out there, it buys a lot of drugs, it goes to people and if they are not at the highest possible standard, then who gets blamed if they are not effective and resistant strains are developed as the consequence? And what comes to mind when one thinks about that is the current uproar in Nigeria over polio vaccines. There have been cases where western medicines have been brought in to deal with medical problems in African countries and if there are imperfections in them it becomes an uproar of another kind. So my question about that is how do you see that argument from the US government? Do they have something to stand on, or is that another thing that you view as a smokescreen for protecting pharmaceutical companies?

Ellen 't Hoen: For your first question, we can send you the text of the [--] which was included in the Q&A on PEPFAR funding on the FDA so that you will have all the data.

Barbara Borst: Thank you.

Ellen 't Hoen: And that was what was published at the time when PEPFAR was presented. The second, as I said, we need effective medicines, we need safe medicines (relatively safe medicines, don't forget that every effective medicine almost always has side-effects), and we need medicines of quality. We do not need the highest possible quality standards that is achievable in the world. We need medicines that are of quality according to what the international standards are. Now that is true for the fixed-dose combinations, but that is also true for every other drug. There is nothing special about the fixed-dose combination. In that sense many of the questions that will be raised in Botswana are not those specific to the fixed-dose combinations. To assure the quality of drugs is important also for the single drug components. Quite often at a country level in developing countries, national regulatory agencies do not have the capacity to judge and deal with a registration dossier of a new pharmaceutical, particularly if there aren't so called reference dossiers available. That is exactly where I come back to the role of the World Health Organization. It is so important to this because the World Health Organization can look at the dossiers of, for example, the fixed-dose combination, or can look at the dossier and assess the safety and the quality of generic versions of medicines. In some cases, fixed-dose combinations cannot be used. We don't mean to say that always and in every case we always should use the fixed-dose combinations (and the doctors on this call can talk about that much better than I do) but for certain patients you will need other components into triple therapy that presently do not exist yet in a fixed-dose combination. The WHO can look at that regardless of the status contrary to, for example, the FDA, who will only look at a dossier when it is submitted by a company. A company only has the interest to submit the dossier when it wants to enter the US markets. There is no interest in submitting the dossier to the US Food and Drug Administration when you cannot enter the market, which at the moment, is the case with the fixed-dose combinations and a number of other generic versions of the antiretroviral.

Kris Torgeson: Thank you, Ellen. Dr. Saleban, would you like to add anything to that?

Dr. Saleban: I would like to ask Barbara if she can repeat her follow-up comments?

Barbara Borst: Yes, Dr. Saleban, I want to be sure I understood you correctly that the demonstration that you see of the effectiveness of the medicines currently being used in your program is clinical observation rather than, you know, a more concretely scientific testing to see whether blood counts and other measures show an improvement in the patient.

Dr. Saleban: Okay, and thank you Barbara. First of all, on the clinical observations, as a participant of this conference I have elaborated the process of pre-qualification of the WHO list at my level in the field. In Homa Bay, which is a rural remote area, I have the only CD-4 machine where I can test the immunological evolution of the patients, before we start and after six months or after 24 months of the viral drugs. So, what I tried to share with you was an immunological evolution of the patients who are receiving antiretroviral drugs. We have observed the mean increase of the defense cells after (indiscernible) six months, and they gained more than 120 cells, and after 24 months of the treatment the patients have gained more than 140 cells. This is what I can share with you -- I don't have a biochemistry laboratory in Homa Bay, because most of the health facilities there have no electricity or drinking water. Thank you.

Kris Torgeson: Thanks. Eric did you want to add anything to that at all?

Dr. Eric Goemaere: We have a bit more resources in South Africa. There is a possibility to use what is considered the global standard for the efficacy, to choose the level of (indiscernible), and we make sure of the viral replication in the blood. We can show whomever is requesting that they have made difference (indiscernible). As far as fixed-dose combination and generic drugs compared to the brand names, we haven't seen any difference in business (indiscernible), again what's considered the global standard.

The comments I wanted to make on what Ellen said is that one has to be aware that fixed-dose combinations are not a new subject -- it's a very old subject. I think it was introduced, (indiscernible) fixed-dose combinations, for more than 10 years. It's a subject that was debated about 20 years ago, and all the technical issues and constraints about making fixed-dose combinations, and the regulatory issues have been debated and agreed upon for a very long time. So I don't know why we should come back to that, (indiscernible) especially since there are already fixed-dose combinations that have been approved by the FDA, as was said before. There is no need to define the technical criteria any more. There is a need of enforcement to make sure that you will (indiscernible) coming into the market, and to make sure that we avoid the catastrophe like you heard about in Nigeria. I think they need to face one to (indiscernible), but this is not a regulatory issue, it's an enforcement issue, and not an issue of (indiscernible) the technical characteristics.

Kris Torgeson: Thank you. Next question please.

Operator: Our next question comes from Joanna Buchan of BBC World Service. Your question please.

Joanna Buchan: Yes, my question is about which companies worldwide, which of the generic companies are manufacturing the fixed-dose combination pills, and which countries they are in? Is there yet a generic company in Africa making these pills?

Kris Torgeson: Ellen, would you like to take that first?

Ellen 't Hoen: Yeah. The companies that are presently producing the generic versions of the triple fixed-dose combination, the three-in-one pill, are Ranbaxy in India and Cipla in India, and they make different versions in different dosages. And for the double fixed-dose combination, in addition to Ranbaxy and Cipla, there is also an Indian company called Hetero, and there is of course also the GSK double fixed-dose combination. I am referring now to the recommended first-line regimen drugs as recommended by the WHO guidelines. Because, as I said earlier, there is also a triple combination by GlaxoSmithKline -- the brand name of that is Trizivir -- but that is not a first-line recommended treatment.

Joanna Buchan: So all the first-line recommended treatments currently come from India?

Ellen 't Hoen: At the moment they do, but as Eric Goemaere explained earlier on the call, there are activities underway in South Africa to start local production or national production of fixed-dose combinations. I don't know exactly what the time schedule for that is. But maybe Eric has information about that.

Dr. Eric Goemaere: Yeah, they are already in the pipeline and waiting for approval from the regulatory authority, and making sure that, as I said before, there is a market developing for them. Because they are not a commercial company, I think that I would do a slight direction in what you said in the (indiscernible) lowest treatment plan they have (indiscernible) to produce fixed-dose combinations. Anyway, it's a good example besides India, which is Brazil and Thailand.

Ellen 't Hoen: And Thailand, yes.

Eric Goemaere: And they have set up an enormous company that is producing fixed-dose combinations mainly for the national market. We are not using them internationally because they have not been WHO pre-qualified and they have not submitted the drugs to the pre-qualification process. As I said, they are (indiscernible) company or biochemical company, but they are just interested in covering the needs for their national market. They are not interested in exporting, so they will not submit to WHO.

Ellen 't Hoen: Yeah. Thank you Eric, that was a very good addition, because I only listed the companies that have been pre-qualified by the WHO and that would want to export the drugs.

Kris Torgeson: Thank you.

Joanna Buchan: Thank you.

Kris Torgeson: Next question please.

Operator: Our next question comes from Ed Susman of UPI. Your question please.

Ed Susman: Yes. At the recent Retrovirus Meeting in San Francisco, there were several studies that indicated successful use of generic drugs in resource poor setting such as Mozambique and Zimbabwe. Have you looked at examining the results of those studies to use as responses to the US objections?

Kris Torgeson: Does anyone feel they have the background of those studies to answer this? Otherwise maybe we can follow-up later on that with more information.

Ellen 't Hoen: I do not, but one of our AIDS doctors was at that conference, so maybe we can follow that up separately.

Kris Torgeson: Yeah, I will follow that up with you Ed, because we do have someone who was at that conference and can answer your question on that.

Ed Susman: Well, thank you.

Sharonann Lynch: Kris, I would like to respond to another earlier question.

Kris Torgeson: Please go ahead.

Sharonann Lynch: It was in terms of where these fixed-dose combinations are --.

Kris Torgeson: Just so everybody knows -- this is Sharonann Lynch from Health GAP.

Sharonann Lynch: Thank you - -not only where the fixed-dose combinations are being produced, but also where they are being utilized. This is not just about the MSF projects. Fixed-dose combination drugs are registered and either in use now, or purchases have been placed -- just taking a glance at some of the recipient countries from the Bush Global AIDS Plan -- in Cote d'Ivoire, Ethiopia, Kenya, Mozambique, Nigeria, Rwanda and Zambia. And you have already heard from Dr. Goemaere regarding the use of other fixed-dose combinations in Brazil and Thailand, where they are basically the mainstay of their national treatment programs. As far the use of fixed-dose combinations and the support for WHO pre-qualification, this is what the World Bank recommends, and it's what the Global Fund to Fight AIDS, TB and Malaria uses. Columbia MTCT-Plus has been using fixed-dose combination drugs. UNICEF procures fixed-dose combinations, UNFPA as well, and the Clinton Foundation, as we all know, negotiated the lowest price available today. It's not only MSF saving lives with these drugs. These are national governments and other organizations, and this has a momentum that should not be stopped by the false science that the US is using.

Kris Torgeson: Thanks so much Sharonann. Any other questions?

Operator: Yes, we do have one more question from Joanna Buchanan of BBC World Service. Your question please.

Joanna Buchan: Thank you. Just one more -- it's Joanna Buchan by the way, but never mind.

Kris Torgeson: Thanks Joanna.

Joanna Buchan: Thanks -- actually I didn't understand why MSF stresses the importance of getting FDC's out there. Here in Britain at the end of the last year, a patient currently being treated in England but originally from Zimbabwe presented drug resistance to all known combinations (indiscernible). And this patient had been buying generic drugs in a private clinic in Zimbabwe, and was going on and off drugs. When he felt better he stopped taking them, and when he felt worse he started taking them again. Drugs procured in all good faith for various programs in various parts of Africa are turning up on the black-market in large quantities. Are there any programs in place or any ways that you can think of that this can be stopped?

Kris Torgeson: Ellen, would you like to address that first? I believe Dr. Eric Goemaere had to leave, so he is --.

Ellen 't Hoen: Yes. I think precisely to avoid these kinds of situations, we need to look at what is necessary. Why do people not take the treatment they need to take? Quite often because they have to take a lot of pills, quite often because they don't have enough money to pay for the entire treatment, or for example they feel that they need to share the medication they do manage to buy with other members of the family, quite often in situations where the supply of these medicines are not managed well. These are reasons, in fact, in support of the fixed-dose combinations, and in support of putting systems in place that assure the supply of quality versions of the fixed-dose combinations, because if your drugs are effective and of quality, you manage to suppress the viral loads to a level that helps reduce the possibility of developing resistance. Of course, in terms of resistance, we have to acknowledge that over time, just like it has happened in the West, patients will develop resistance to these medicines, even if they are used in the most correct manner. That is why we also have to look at what will be the second-line treatment and what will be the third-line treatment, and new drugs that are being developed. How can they be made available in such a way that they are affordable, because affordability is very, very important. When drugs become affordable, they can be used on a larger scale within the existing health care systems. And patients will not need to go out and buy whatever happens to be available on the market.

Kris Torgeson: Thank you. Would anyone else like to follow-up on that question? If not, are there any other questions?

Kris Torgeson: If not, I think we will end the call here, unless Sharonann or Dr. Saleban have any other remarks you would like to make before closing? If not, I think we will end here. Thank you everyone for coming on. And if you have any follow-up questions you can reach me at 917-913-0183, and that's country code +1-917-913-0183. You can also reach Sharonann Lynch of Health GAP at 646-645-5225, if you have any follow-up questions and we will be getting the other supporting material out to you as soon as we can. Thank you so much.

Operator: Ladies and gentlemen thank you for participating in today's conference. This concludes the program, you may all disconnect. Everyone have a great day.