An Interview with Professor Brian Gazzard
photo source NHS: http://www.chelwest.nhs.uk/hiv-sexual-health/sexual-health-information.html
2008 marks the sobering 25th anniversary of the discovery of the Human Immunodeficiency Virus (HIV). From the outset, Professor Brian Gazzard has been on the frontline. Over the years his career has seen him as the founding chairman of the British HIV Association (BHIVA) and chairman of the Expert Advisory Group on Aids (EAGA) to the government. Alexander Hills and Kapil Sugand caught up with him at the St. Stephen’s Clinic (Chelsea and Westminster Hospital, London) to ask him about his journey in HIV medicine so far and the challenges that lie ahead.
When did you realise this was a new disease?
I saw my first HIV patient in 1979. It is controversial whether this was the first case in the UK, but in many senses it is irrelevant. There were most probably cases in sailors up in Manchester back in 1959, let alone cases in London, but we did not know what the disease was. I was studying cancer of the colon at the time when Adam Laurence, who was a very well known STD doctor, sent me a patient who apparently had secondary syphilis, but things did not all fit together. When we gave him penicillin he got progressively more ill with gingivitis, all his teeth fell out, he lost weight and it was noted that he had lymphadenopathy, which we obviously biopsied. At we one point we thought he had Whipple’s disease so he also underwent a laparotomy.
We did know fairly early on that he had no T-cells because Jack Hobbs, a Professor of Immunology, had the only machine available in the country capable of doing this, and he actually tested this. So initially we didn’t know what was going on.
Then my senior registrar, who was in San Francisco on secondment at the time, wrote to tell us of this new disease that was spreading across the country characterised by PCP (PJ). I looked it all up and checked out the relevant radiographs. The very next week the patient came back in with classic PCP X-ray features and was treated accordingly. He turned out to be part of a very large sexual network of patients, all of whom subsequently presented to me with lymphadenopathy and weight loss, and we subsequently wrote a paper on these cases in The Lancet just before the antibody test became available.
What was it like trying to manage the first of these new cases?
Of course initially there was a mixture of fascination, horror and dread. In the early days doctors thought that they themselves may be greatly at risk of infection, I myself gastroscoped about five or six hundred people not knowing if I was at risk or not. Secondly they presented with a variety of unknown diseases and opportunistic infections, which we now recognise, but in those days were extremely rare. They were the sort of things that you find in the tiny bits of text books that you never bother to read because it was a post script, so rare that it would never happen.
Of course it was also exciting at the time as well because we shared knowledge; all the early conferences were describing new conditions and new ways of treating it. I also think it was exciting because we were able to be really good ‘doctors’ again. If you go back to the time of Osler, where Osler has described all the alga rhythms for care there were to be, life was going to be very boring, yet this new disease comes along and actually allows you to describe the best way of managing symptoms, diagnosing individuals etc. I feel it gives hope for the future, as there are many new diseases that need to be further defined. Some of them are very common, for example non-alcoholic steatohepatitis, which is a really interesting disease to do research on, as is the warts virus, really thought to be very unimportant a hundred years ago, but now clearly very important. Nobody understands why the vaccine works and the whole natural history of warts I think is also very unclear. It gives students hope for the future that they can still train as doctors and do what doctors are best at, diagnosing and treating patients.
What has been a revolution in my life-time is that I started off making sure HIV patients could die with dignity, with as little pain as possible, and now I can tell them that they will all be able to live a normal life-span, if they take the pills when I tell them too. This is a really amazing thing, and I don’t think that there will be many diseases where this happens.
How long did it take to realise the extent of HIV spread?
I think that shortly after the epidemic first started it was appreciated, largely due to having amongst the best data on an infectious disease we ever have really had. HIV was originally found in drug users and people who were exposed to contaminated blood, making it prominent amongst haemophiliacs, and of course the disease was also described very early in sub-Saharan Africa as ‘slim disease’, which probably turns out to be a condition secondary to Criptosporidiosis and Candida.
We were very lucky that within two or three years of the epidemic starting we had found the virus that clearly causes it. Then very quickly we were able to produce an antibody and to then define very clearly those who had been exposed and so the enormous scale of the epidemic in sub-Saharan Africa was realised. In the UK, at least initially, HIV was mainly found in men having sex with men, and in much of the Western world it was the same, but with a rather variable concentration in drug users, depending on whether needle exchanges were available.
Are major pharmaceutical companies and governments doing enough?
The pharmaceutical industry is often pillory for its response to HIV, I think it is unfair. I feel that by and large most of the best drugs are developed as a result of capitalism, very few drugs have been produced as a result of socialism and very few drugs have been brought to market as a result of basic research. That is not to say that basic research is not important, but it is more to say that the money motive to get a successful drug has been very important. Pharmaceutical companies have responded pretty well to the epidemic in Africa, perhaps for altruistic reasons, public relations reasons or perhaps because they felt they couldn’t do anything else. The situation is now many of the drugs are available at cost, whatever ‘cost’ means. ‘Cost’ means different things to different people, and if there are lots of people even very small profits will add up to large profits. However, I think they have done really quite well encouraged by UN aid, and by the Clinton Foundation.
I very much admire the Clinton Foundation and their capacity to use business people to leverage results as I think that many of the problems in HIV, in Africa, are business related, like logistics, continuity of supply and encouraging people to take these drugs.
I believe governments have done as little as they can possibly get away with, which is often the case with these things. The trouble with democracy is that it’s very short-term, this means, for example, global warming is difficult to get on the agenda unless it will affect us this year or next year, and it’s the same with HIV. HIV was considered to be on the verge of killing everybody, so governments respond. Then they find that it is not going to kill everyone, just a disadvantaged group of the community that nobody cares all that much about. This kind of approach has caused enormous problems in Africa.
The view that Africa is a hopeless cause, where they could not do anything to help, was very prevalent, so I think governments were very slow to respond. Governments are now responding and talking about the disappointment of the total amount of money being involved there and I think there is a disappointment about the promises made versus the actual amount of money in fact given.
Personally I believe that money is now not the problem, only part of the issue, with it being much more about logistics, continuity of supply and people on the ground able to give the drugs. There is a very reasonable incentive in a way for those who are competent in these countries to move somewhere where the standard of living is higher, which you can’t blame them for but is counter-productive.
The response to HIV has been very complicated and it remains as much of a problem as global warming. I would like to draw attention to the fact that though there are many diseases killing many people, HIV remains an epidemic. This means the numbers will not stay constant like they do with malaria; instead they can become an enormous epidemic force. On a time scale more than our life-time, clearly the effect on the entire community is potentially huge. As an example if you look at chimpanzees, about a million years ago it was probably a retro-virus that decimated up to nine tenths of all the chimpanzee population. Therefore, the very narrow repertoire that make up MHC-class antigens on chimpanzee cells probably reflect their response to this previous retro-virus.
Clearly over what is a very short-term evolutionarily, but long-term politically then HIV may have a devastating effect for human kind.
How close is a cure?
A cure is probably a long way away, but as with many things when you are sitting in the morass you do not know what is going on, but when something new happens it all becomes clear. The best example of this is Cox’s postulates which enabled bacteria to become clearly understood, but also caused everything to became a muddle as a lot of clearly infectious diseases could not fulfil the postulates, leading to a lot of awful literature in 1910’s and 20’s. Then viruses were discovered and the whole thing became much clearer. I feel the same may happen with HIV, and that there is a ‘missing link’ in our understanding on the immunology of HIV. It may be here that basic research may be very useful in uncovering a new fundamentally important principle that may illuminate the whole of HIV and virology. So, in a way a cure is always unpredictable, though my personal opinion is that it is a long way away.
What are the current challenges this field faces?
The current challenge, first of all, is prevention, so far it has been very disappointing. Phase 3 trials of vaccines have all failed and one actually looks as though it has encouraged HIV infection to occur. Other phase 3 trials of microbosides, have also resulted in failure, with a tendency for the users to get more infection. Studies looking into prevention using diaphragms and by trying to suppress herpes infection have also come back negative. Looking at the success of behavioural change, such as abstinence, being faithful, using condoms and measures of increasing knowledge, it is very difficult to tell the quality of the data on studies and whether they are really influencing the epidemic.
One of the things I always thought was underused, but most important in HIV, was the ‘Jaipur paradigm’ introduced many years ago in India. It states very clearly that the epidemic size will depend on two factors: firstly the economic strength of the community and secondly the degree of cohesion of that community. In other words, if you have a very cohesive community, for example if they all go to Church or Mosque every Sunday, then there is a very small epidemic.
I was very struck when I went to Montserrat 20 years ago, on Monday there was nobody on the streets at all. I drove in a taxi through empty streets; they were all singing songs in practice for church on Sunday. In such a close community, it is very difficult to be promiscuous, but more importantly there is a sense of uniformity in trying to tackle the epidemic. Therefore you can argue well that in Uganda with the arrival of democracy and sense of fair play in society means a smaller epidemic and that in Thailand, being a cohesive society with great leadership has its effects on the HIV epidemic there as well. This is in contrast, I think, too much of southern Africa, which tends to have very corrupt societies, rife with war and dissension; with HIV being only one of many problems, allowing the epidemic to grow. So it is not just prevention per se, it is not just behavioural change but it is also economic and political changes which are important in prevention.
We also underestimate the great importance that the anti-retrovirals have in prevention. The Lancet published a very well-known paper, which I thought was wrong at the time (and still think is wrong), that prevention was the only route, we could not afford anything else and that treatment was not going to be available in Africa; this was totally wrong, treatment is now widely available in Africa. Probably three to four million people in Africa are now on highly effective treatments with very good adherence rates. This has had a potentially major effect on prevention.
HIV is a totally treatable disease, and paediatric AIDS should have disappeared. The cost of drugs to make paediatric AIDS disappear is miniscule, but it does not happen. This is because the mothers do not want to be tested themselves, as there is no treatment. However, as soon as there is treatment available, testing rates have gone very much higher. So prevention and treatment really are going hand in hand, and treatment may have a very important role in reducing the size of the epidemic. There is also good data showing that if a patient’s viral load is negative they are much less likely to transmit HIV, although there is controversy from the Swiss Commission as to whether that ‘negative’ result is zero or just very low. In public health terms it does not matter, since the risk is clearly very low and though that does not give you advice about the individual, it indicates that in a community it is likely to reduce the scale of the epidemic providing a large number of the population who are HIV positive and sexually active are covered. Unfortunately, treatment will not cure the whole problem, because sero-conversion illness is the primary route of transmission, with probably 50% of all transmissions occurring in those first few weeks. Therefore you will not prevent sero-conversion directly by giving treatment but you will have an indirect effect on the sero-conversion rate for subsequent rounds of infection.
What advice would you give to those considering a profession within HIV medicine?
This is a wonderful career. The epidemic is very much changing from a group of very sick patients who are dying to a group of largely very well patients who need long-term treatment. Management issues related to long-term treatment are psychological, sociological rather than acute medicine, so there will be little need for a group of doctors who are very interested in both acute medicine and difficult diagnoses but a much larger need for a wider range of doctors who are capable of persuading people to take treatment year in and year out, making sure that they have the best treatment and keeping up to date etc.
The speciality will change, clearly genito-urinary medicine is still a very good route for people as problems are often sexually related, and the ability to discuss that in a very non-confrontational, non-judgemental way is very much a genito-urinary medicine strength. I think that there are many other routes as well: general medicine is very useful for people to look after the sick end of the spectrum, so training in that remains very important. Obviously being an infectious disease the training you get from within infectious disease specialties gives you all sorts of insights, particularly research wise on how to manage HIV.
In reality, there will remain a number of different routes into HIV medicine, but I think an add-on specialist qualification with an exit exam of some sort will come about. It is already beginning to occur with the HIV diploma of medicine, but I do not think there will be a full exit exam just yet. Already the standards needed from that exam, if you want to pursue a career in HIV, are being advised by BHIVA (British HIV Association) and other groups. In due course I think they will want an exit exam, alongside some degree of experience within a large HIV unit.
Dr Alexander J Hills MBBS, BSc (Hons)
Mr Kapil Sugand BSc (Hons)
kapil.sugand04@imperial.ac.uk