The Body Covers: The XIV International AIDS Conference
A Roundup of Barcelona
July 13, 2002
There is a story about a royal painter in Spain who was painting a portrait of the king. When the king complained that the painting looked nothing like him, the painter said, "Don't worry, Your Majesty, in 300 years it will." Sometimes I feel that it doesn't matter what really happens in these conferences, because what happened, in the end, is what The Body, HIV InSite, Medscape, NATAP or HIV and Hepatitis said happened.
Barcelona is a beautiful city, and this would be true even if I weren't biased (I was born here). I never realized before how beautiful and alive Barcelona is. I took it for granted. Ironically, that did not help my conference experience because it was distracting. There were so many things to do that many people took the opportunity and came here more for tourism than for the conference itself.
The conference was also too big, with more than 15,000 participants and more than 10,000 posters. It was impossible to be really productive, but this is characteristic of all International AIDS Conferences. "Overwhelming" was the most frequent comment made about the conference. I always had the feeling that I was in the wrong place, that I was missing the talk that I should not miss, or that I picked the wrong seminar. The geography of the conference did not help either. The plenary sessions were in the Palau Saint Jordi, which is 25 minutes away from the other conference locations.
The science -- at least the clinical part -- was very good this time, much better than in Durban or in Retrovirus this year. Major trials like ACTG 384, INITIO, Gilead 903 and the TORO trials were presented during the Barcelona conference. These trials will mark the next months if not years of HIV treatment. In spite of that, many people said that it was not like Durban, because it did not have the "magic" of that meeting which opened all our eyes to the realities of AIDS in Africa and in the developing world.
I was asked to summarize this meeting and I will try to give you my personal impressions, but undoubtedly I will miss a lot. My narrative, I'm afraid, will be a bit chaotic and overwhelming, like the conference was.
During the last day of the conference, there was a summary session of the entire conference that helped me organize my thoughts. It was the most organized part of the whole meeting and brought unity and closure. I really think it should become a fixture of future conferences. It would also be a good idea to have a similar session at the beginning of the conference to help create excitement about the content of the conference itself. It was too easy for people to say that there was nothing new during the meeting. They were wrong: the content was good, it was only difficult to find.
The conference was divided into seven tracks and I will try to highlight what I think were the most important things for me. My perspective was heavily biased toward presentations in Track A and B (the Science and Clinical tracks). (Sorry about that for all of you whose interests are different.)
In the first presentation of Track A (Basic Science) that I attended, Robert Siliciano set a somber tone with his talk about HIV reservoirs and the impossibility of flushing these reservoirs with current antiretroviral therapies. These reservoirs are also an archive of the antiretroviral resistance history of the patient. In another presentation on pathogenesis we heard about recent findings that HIV selectively infects the cells that are supposed to clear the virus itself, making the immune system's fight a very difficult one, and, in most individuals, a losing battle. There was, however, good news in this track: the development of new drugs targeting the entry process and other drugs (more for the long run) that will help control viral replication by targeting the cellular proteins which interact with viral factors. I am optimistic that new and better drugs will be developed in the future. Just look at all the new drugs that have been developed over the last few years which are much better and easier to take than the old ones.
One of the most important talks was Bruce Walker's discussion on the immune system. He presented one case (it is amazing how much we can sometimes learn from a single case!) of a patient who had been treated during acute infection and showed a very good immunologic response against the virus (by all the parameters that we can measure and currently target for a potential vaccine). This patient then maintained an undetectable viral load on no therapy. Subsequently he was infected by a different virus (or had an escape of his own virus -- it really does not matter) and began to experience disease progression. A case like this is extremely disheartening regarding the prospects of creating a protective vaccine, and implies that -- for the foreseeable future -- we will always have HIV-positive patients -- sad news for me. On the positive side, we also learned -- using models of the epidemic -- that we might not need a completely protective vaccine, that a vaccine that provides partial protection might help curtailing the pandemic.
Therapeutic vaccines seem to offer more hope. I was really impressed with the data that J. Lisziewicz and Franco Lori presented about DermaVir, a therapeutic vaccine for patients already infected with HIV (ThPpA2128). This is a skin-applied DNA vaccine that has worked well in an animal model of SIV in combination with treatment interruptions. This vaccine is entering Phase I trials in humans within the ACTG system this fall. It has the beauty of simplicity. Simple things deserve to work.
Track B, the clinical science part, had a lot of news. For me, the biggest news was the death (or close to it) of protease inhibitors as first-line therapy, at least the current protease inhibitors. Prospective trial after prospective trial and retrospective analysis after retrospective analysis has shown that NNRTIs should be the preferred first-line regimen. ACTG 384 from the U.S. and INITIO from the rest of the world were very consistent in this regard. Somebody can say that they did not compare efavirenz against the most potent PI lopinavir, but even if these two drugs are equi-potent, it is likely that clinicians will select efavirenz as first-line therapy because of the better toxicity profile. In that regard, the data from a massive Italian study showing an increase in the frequency of coronary events in patients taking PIs when compared to NNRTI regimens was really revealing (WeOrB1307). [Note added after the meeting: There has been a lot of controversy about this presentation and the main author Dr. Barbaro. On July 11, 2002 the New England Journal of Medicine (NEJM) retracted a paper from Dr. Barbaro published in 1998 (NEJM 2002; 347:140). This is an extremely unusual step, and I do not remember ever seeing something like this in my whole career. Apparently, the paper of Dr. Barbaro included a microphotograph from a previous paper by a different author which had been copied and manipulated by Dr. Barbaro. Dr. Barbaro did not comment on this, but the evidence is overwhelming, suggesting that the 1998 photograph is a manipulation (which is why the paper was retracted by the NEJM). After the meeting, several investigators raised questions whether the trial presented in Barcelona was really a prospective trial and raised some credibility issues. In light of the problem with the New England Journal of Medicine article, I leave it to the reader to draw his/her own conclusions about this presentation.] Only the problem of primary resistance to NNRTIs or the development of new drugs or PIs with better toxicity profiles will reverse this trend.
Guidelines, as usual, are late in reflecting the fact that NNRTIs are the preferred first-line therapy, but guidelines are almost by definition late. They are good tools for clinicians without lots of experience who have some patients with HIV, but experienced clinicians find them less useful. What can you say -- they still recommend the combination of AZT and ddI as a reasonable dual nucleoside regimen with an NNRTI or a PI. It has been several years since the last experienced clinician has used that combination of nucleosides in any naive patient. The problem is that no major trials are using that combination anymore, so in the absence of negative evidence, the recommendation stays. This is one of the many problems (it has many virtues also, do not get me wrong) of the so-called "Evidence-Based Medicine." Sometimes I think we should rename it "Eminence-Based Medicine" (since it relies too much on the opinion of "eminences" who don't see too many patients, and on old but well-designed trials that have lost relevance in the current environment. They do not rely on good old-fashioned clinical expertise, which, at least in the HIV arena, seems to always predict what is going to happen in the near future. I will give just a few examples: Clinicians realized quite early on that therapy with three drugs was better than two-drug therapy. The guidelines, however, needed to wait until ACTG 320 was presented. Clinicians also realized that the toxicities of these regimens were too much for patients treated early, and as a result, they became more conservative long before the guidelines did -- an approach that has been confirmed in multiple large retrospective studies, and that the guidelines now reflect. Clinicians also have been using NNRTIs as the preferred first-line therapy for a couple of years now. The guidelines will probably reflect that next year.
Tenofovir was one of the central players at this meeting. Tenofovir is an extremely promising new drug that can be used both in naive and experienced patients. The results of 903 (LbOr17) are really impressive and equal to d4T as part of a combination with 3TC and EFV, one of the most popular combinations of the last few years. One interesting result of that trial was the difference between the arms in triglyceride/cholesterol levels over time, with lower levels in the tenofovir arm. However, I found it misleading that Gilead, the company that developed tenofovir, did not inform us (either in the poster or in the presentation) that those were non-fasting levels, which implies that those results will need to be subsequently confirmed.
T-20 is another extremely promising drug, and the TORO trials (LbOr19A, LbOr19B) show that it will become an integral part in the management of patients with MDR virus. Many studies were presented supporting boosted PIs, even as part of triple-PI combinations, as very potent drugs for patients with virologic failure. Many new drugs were presented and a terrific presentation was given by Robert Murphy on Monday (MoOrA141). I will not review all of them in detail. Interesting data was presented on atazanavir and amprenavir, which has cross resistance opposite patterns; if a virus becomes resistant to atazanavir it is hypersensitive to amprenavir and vice versa. Pedro Cahn thought this might be important for sequencing in the future.
There was also good news for patients with a multi-drug resistant virus: Julio Montaner provided data that suggests that those patients have a much lower mortality than historic controls and are not very different from patients who are responding to therapy. This may be related to decreased fitness of the virus, as Steven Deeks has suggested a while ago.
One of the biggest surprises for me was that drugs could be given in resource-poor settings with exceptional results. Two very moving presentations, one a plenary from a doctor working in Haiti and one from a non-governmental organization (NGO) in South Africa highlighted this fact. Brazil sets an example for what the government of a developing country can and should do for their citizens regarding HIV. However, it is important that we do not forget that the prevalence of HIV in Brazil is 1 percent and in a country like Botswana it is 35 percent, so we are clearly talking about very different realities.
I did not attend many sessions in Track C (Epidemiology), so I will rely on what others thought was important. New assays have been developed to detect recent infections, and in Europe and the U.S. the transmission of drug-resistant strains is very, very worrisome and could affect the decision of what to start therapy with. The sobering news in this track was that the epidemic is ramping up in many parts of Africa and Asia and that the number of orphans is on the rise. If we do not do something the situation will only worsen.
There were new data about the interactions between sexually transmitted diseases and HIV, and how co-infection with HSV2 increases the risk of acquiring HIV. HIV also interacts with other pathogens like tuberculosis and malaria. HIV infection doubles the risk of TB very early after infection, even before severe immunodeficiency occurs. Malaria increases the HIV 1 levels when parasitemia is present. The clinical implications of this are less clear.
Then there were some miscellaneous tidbits that I thought were interesting: Semen HIV viral load levels during acute infection are similar to plasma and tend to be extremely high. It might be a period of high infectivity. Good news regarding the response to therapy of different clades of HIV: progression does not seem to be different depending on them. Drug users probably do not respond as well to HAART as other groups, but there could be many confounding factors with this finding.
I didn't get to see much in Track D (the Prevention track). Although, it is clear that education can decrease risky sexual behavior, it has become evident that education has a limited effect and durability. Data of increased risky sexual behavior in San Francisco among young gay men are worrisome, and a lesson that the availability of therapy might not translate into a decrease in infections. Gender and culturally sensitive interventions improved sexual behavior in many studies and seemed like a good approach. Voluntary counseling and testing, especially for males in the developing world, have to be an integral part of any program to prevent the further spread of this devastating epidemic. The treatment of sexually transmitted diseases might help prevent HIV infection, but the results of the trials are controversial. Microbicides is an area of excitement, however, results are preliminary and not very promising so far. POZ magazine talked about a life beyond latex, but my feeling is that it's still a lot of wishful thinking.
Track E (Social Sciences) made us more aware than ever that politics is important in curtailing this epidemic. During this conference the presence of activists was much more apparent than in Durban. They destroyed several drug company and government booths in the exhibition hall and boycotted several talks, including the Spanish Minister of Health (who lost her job the following morning for unrelated reasons) and the U.S. Secretary of Health, Tommy Thompson. Activism plays an important role in driving political proposals, but sometimes it is simply annoying. During the closing plenary lectures, activists entered the room and chanted for 20 minutes during the summary lectures of Tracks D and E, making it impossible for the voices of the two speakers to be heard. They were chanting (in Spanish, so many people did not understand it: "Mujeres adelante, estamos aqui" -- "Women move forward, we are here") for 20 long and very boring minutes. Ironically the two speakers who could not be heard were women. I really could not understand the whole purpose of that silly exercise.
There was a lot of talk about empowerment (more than 200 abstracts included that word in the title), social justice and human rights. HIV drugs are not a commodity; they are a right for the infected population of the world. This was one of the most applauded statements of the conference.
The new Tracks F (Interventions and Program Implementation) and G (Advocacy and Policy) presented both data about the response to the epidemic in different parts of the world like Brazil, South Africa and Haiti and comments on the importance of targeting difficult-to-reach populations like drug addicts or young people. Programs with needle exchange injection rooms have been a success in countries where drug abuse is the main form of transmission. Programs targeted to youth have helped improve self-esteem, respect from parents and safe sexual behavior in this very difficult-to-reach population.
The meeting concluded with an extremely long ceremony, that to make things worse was almost an hour late. I will only highlight three speakers -- Stephano Vella, the president of the International AIDS Society (who is leaving his position this year), is a great and very sincere speaker who delivered on his promise in Durban to bring this conference back to the developing world: The next international AIDS conference will be held in Thailand in the year 2004.
Bill Clinton gave the best political speech in this conference. He is a fascinating and very imposing politician. I was afraid that activists would not allow him to talk, but he silenced them very quickly. He talked about the need for the world's rich countries to commit resources to curtail this epidemic which has become a global threat. He also mentioned something that I think is probably as important as that, which is the need for the developing world's commitment to this task. Corruption, lack of basic human rights, political instability are some of the things which have plagued foreign aid to the developing world, and that should not happen to foreign help for AIDS. We need to work on both ends of the equation. That is why non-governmental organizations will play such an important role. Clinton advised all of us to continue working and never give up on anybody, citing the example of Jessie Helms and his change of opinion about the issue of AIDS. It was a very moving and wonderful speech.
Then Mandela talked. Mandela is such an icon that it doesn't really matter what he says. He looked older than in Durban and I found his message a little bit more confusing than Clinton's speech -- maybe because I have been so sleep deprived over these five days. It was more a message of individual change and commitment to curtail this epidemic with too many anecdotes to make a strong universal point. In any case, he is always a catalyst and everybody was very emotional that he was there and discussing this issue.
The conference ended with the usual speech about the next conference, but by that time everybody was running out. Future conferences should learn from the examples of Durban (where the same thing happened) and Barcelona, and make these closing ceremonies short and sweet, and send everybody home immediately after the last big speaker (this time Mandela) talks.
This article was provided by The Body PRO. Copyright © Body Health Resources Corporation. All rights reserved.