Joseph's POZ Blog

House of Numbers is the title of a documentary film which according to its promotional material will "rock the foundations on which all conventional wisdom on HIV/AIDS is based" 

 I have seen the film.  It is completely unable to achieve this grandiose objective.  It is in fact an AIDS denialist film, despite the contention to the contrary by Brent Leung who made it.

  The denialists are a disparate group who remarkably continue to believe that HIV cannot be the causative agent of AIDS either because it is harmless or because it does not exist. There are even those who believe that AIDS itself does not exist as a distinct disease entity.    Of course there is no shortage of people with strange views that fly in the face of solid evidence.  We can mostly just ignore them.  But sometimes these views can be dangerous, and then we really do have to confront and challenge fallacious assertions that can lead to harm.

The Spectator is a weekly UK publication that had arranged a showing of the House of Numbers to be followed by a panel discussion of the film with audience participation. I had agreed to be one of the four panel members together with the filmmaker.  Several people asked me not to participate in this event, probably with the thought that it was wrong to associate in any capacity with individuals who hold such outrageous views.  There was also much activity on  UK blogs,  generally denouncing the Spectator event. It seems that a lot of people just did not want it to happen.

Two of the panel members withdrew so the event has now been cancelled.   This is a pity.  The film is as I said, dangerous.     It is dangerous specifically because it presents antiviral treatments as only toxic with no mention of their benefits.  Therefore it is justified to be very concerned that some people who need treatment may be dissuaded from receiving it after seeing the film.

I do accept that it is right to not prohibit individuals from expressing their views, no matter how distasteful.   But when these views carry danger it is particularly important that they be challenged with valid information.   It is absolutely wrong to ignore the film and allow it  a free hand in spreading misinformation.   As I have experienced when I was a member of President Mbeki's panel in S. Africa, it is impossible to argue with those who hold such denialist views.  They are impervious to reason.  It is therefore pointless to engage them in discussion. However, when their position is presented to the public, then it is right to try to expose the fallacy of their views to those who might be influenced by them and thus may come to harm as noted above regarding HIV infected people in need of treatment.

I should explain why this is definitely a denialist film despite the protestations of its director that it is not.

In providing a more or less equal, uncritical  and essentially neutral platform to those holding denialist views together with those who do not,  the filmmaker,  presenting himself as an unbiased observer merely asking  questions,  puts forward the impression that the issue of HIV's role in causation remains unsettled.  Although the film does not explicitly reject HIV as playing a causative role in AIDS, it most certainly leaves one with the impression that this, and even the existence of the virus, is merely conjecture.  This is a misleading presentation of the well established causative   link between HIV and AIDS as something that is just a theory, on a par with the theories of Dr Duesberg or of those who claim that HIV does not exist.

This is absurd and as I explained, also dangerous.

Conventional wisdom is absolutely sound regarding the existence of HIV and of its causal link with AIDS.    However not all conventional wisdom is so secure (in my opinion).   Mr Leung does point to some real controversies in HIV medicine.   But these are conflated with issues that are firmly settled.

I have had a pretty conventional training as a microbiologist and as an infectious diseases physician. 

From this perspective and accepting that AIDS is an infectious disease with HIV as its causative agent, there are several  controversial issues, where scientists and physicians do not speak with one voice.

We have to remember that this disease only came to our attention about thirty years ago.  There are bound to be controversies and disagreements as our knowledge of the disease and of its causative agent increases.   Researchers are not exempt from a perfectly human proclivity to make generalizations based on far from complete information.  In science this is a desirable activity as sometimes these generalizations prove to be fruitful hypotheses that lead to new discoveries.  On the other hand they can just lead to a dead end and may even retard progress.  Understandably, as long as information remains sketchy, such generalizations will be associated with legitimate controversy.   I'll just describe a few of the problems that I see as legitimate.

The film presents several   researchers who have opposing views on the role of co-factors.    Some researchers interviewed are adamant in their insistence that for AIDS to develop, co-factors are required in addition to HIV.  Others are equally confident that they are not needed.   

This may sometimes be a spurious conflict arising from differences in how the term, "co-factor" is understood.

AIDS has accrued its own peculiar terminology not usually seen in other infectious diseases. Co-factor is one example, or an infectious agent referred to as the "sole" cause of a disease.

In all infectious diseases there is an important distinction to be made between infection and disease.  Epidemiologists are concerned with theories of disease causation and recognize this distinction very clearly.  The attack rate is the parameter used to define the proportion of people exposed to an infectious agent who become ill.   The attack rate varies from infection to infection.   Rabies may be the only infectious disease with an attack rate of 100%.   

 We rarely know exactly what will determine the difference between an asymptomatic infection and one that produces overt disease. But we do know the general categories of influences. These concern both the organism and the host.  The virulence of the infecting organism, the size of the infecting dose or the way it is introduced into the body can all influence the outcome.

 Examples of host factors that can play a role in determining whether or not an asymptomatic infection will progress to a disease are the nature of the immune response, genetic characteristics, concurrent infections that affect susceptibility or  exert a synergistic effect.  

 It is the complex interplay of host and microbial factors that determine whether for example, one individual infected with hepatitis B virus will remain completely without symptoms and only know infection had occurred when antibodies to the virus are later detected, while in another individual infection results in fulminant  clinical hepatitis.  

HIV disease which includes AIDS is an infectious disease, resembling other infectious diseases.  In all of them, there are determinants of infection, factors influencing the attack rate which is almost always under 100%, and usually a variable course in disease progression.

The term co-factor when used by some could mean all these usually unknown host factors that influence the attack rate.   To others it may mean something specific - even if as yet unidentified, that is necessary for disease to develop in HIV infected individuals.   Used in the latter sense, it would represent a position close to that of the denialists, because it suggests that HIV is harmless in the absence of these other specific factors.   But when used in the former sense it would represent a more traditional understanding of infectious diseases.   

A closer questioning of those asked about the role of co-factors may reveal that there is in fact no disagreement on this issue.

 Those of us who accept HIV as the cause of AIDS should probably not use the term co-factor at all, and discuss AIDS as we would any infectious disease, where we understand that infection and disease are not synonymous. 

AIDS research is subject to all the pressures and influences that can affect any enterprise conducted by people whose incentives will be varied and complex.  Of course there will be instances of conflicts of interest and examples where legitimate criticism can be levelled at some researchers and commentators.   For example, case estimates have sometimes been presented as real numbers.   It is of course necessary to make such estimates when widespread testing is not feasible, but numbers should be clearly presented as estimates when that is what they are.  

  There are also technical issues where opinions differ.     Such perfectly understandable instances are exploited in this film to question the reliability of some solid achievements in HIV medicine.  We are without doubt able to detect antibodies against HIV. This ability is brought into question as the film would have us believe, because scientists may differ about which of the many tests available, alone or in combination, are the best ones to use in a particular setting.  

But because some researchers and commentators may be open to criticism on some points, it most definitely does not follow that they are mistaken on the general issue of causation.

Finally, I should explain why this film is also offensive to some of us.    There are many individuals who owe their lives to antiviral medications.  I have treated hundreds- into the thousands, of people with this disease since it was noticed in 1981.  I could have introduced many people whose lives have been saved to  Mr. Leung, so that their (or others) testimony might have been included in the film.  

My own experience as a physician is just at odds with the picture presented  concerning antiviral treatments.

  It is hard to adequately convey the feelings of a physician who was able to finally help his patients in the mid 1990s, having lost hundreds to this disease before that time.  By the time these drugs became available about 400 of my patients had succumbed to AIDS, a dreadful rate of mortality.  The effect of these drugs was life saving to those with advanced disease whose survival had been limited before.  The portrayal of these drugs as in effect only toxic is so unfair.  I can say with some dismay that had my patients who needed treatment been dissuaded from receiving it by this film, many would surely have died. So this aspect of the film is deeply offensive. 

When I asked the film-maker why he had not interviewed any HIV infected person who had benefited from treatment, his response was:  Are there people who can tolerate these drugs?   So much for the intrepid reporter merely seeking the truth. 

 The fact that the drugs have toxicities and may not always be used wisely does not detract from their great benefits when used appropriately. This is not different to the treatments of many other diseases.  Also, these anti HIV drugs are able to substantially reduce the transmission of HIV from mother to infant.  This great achievement is not mentioned in the film.

It is notable that the denialist/dissident groups include no physician who is experienced in the treatment of AIDS.   One German physician is interviewed in the film who states that his patients with AIDS are well without treatment.   I believe he does not specialize in treating this disease and may only have very few patients with it, but was not asked about  the extent of his experience.   I too was interviewed for the film.  I can't remember if I was asked about my clinical experience. If I had been, my responses were not used.

It is absolutely correct that Mr Leung should be free to express his particular views on this disease.  However we do have a responsibility to counter the dangerous misinformation in the film - specifically, that antiviral medicines are only toxic, with no mention of their benefits.

 I'm sorry the Spectator event had to be cancelled and so an opportunity to challenge the misinformation in the film was lost.  There is nothing more powerful than the personal testimony of individuals whose lives have been made possible by anti HIV medications, as well as that of the doctor who prescribed them.  Had this event taken place, at least two HIV positive individuals on antiretroviral therapy would have been in the audience and would have spoken about the immense benefits they received from their treatment. 

In my introductory post, I promised to write about some of my experiences in New York City at the very start of the epidemic, from both professional and personal perspectives.

This post is about preventing Pneumocystis pneumonia in AIDS. 

It's a sad largely neglected history.  Many lives were shortened before 1989 when  interventions to prevent this type of pneumonia  were finally recommended by government officials for people with AIDS.

Thankfully, with the widespread use of antiretroviral drugs, many people may not be too familiar with this opportunistic infection.  It most certainly has not gone away, but in the 1980s Pneumocystis pneumonia was what most commonly killed people with AIDS.

  It's now almost 30 years since the epidemic was first officially recognized in 1981.  It was in the June 5^th, 1981 edition of the Morbidity and Mortality Weekly Report (MMWR) published by The Centers for Disease Control (CDC), that the first cases of Pneumocystis carinii pneumonia (PCP) were first  described.  Click on this link to see an account of the first official report of AIDS, and the CDCs earliest responses.  First report of AIDS.   

In fact, this CDC report was not the first public mention of AIDS.   The first time the as-yet unnamed disease was noted in the media  was about three weeks earlier, on May 18^th in the New York Native, a gay weekly newspaper in New York City.  Larry Mass was the author of this report.   As noted by Gabriel Rotello, it was the gay community in New York City that first brought the epidemic to public attention. 

Many of us taking care of gay men in the late 1970s became aware that our patients were showing a number of unexplained signs and symptoms.    I was one of these physicians and so  I suppose I should have  started these accounts of the early days  at the beginning - at least, the beginning for me, as I became aware around 1979 that something very unusual was affecting so many of my patients, and  realized that there was a developing problem with potentially immense implications.  But I will leave this "pre-AIDS" account for another post.

 In this post I address the preventable opportunistic infection,  PCP that was the major cause of death among people with AIDS in the first decade of the epidemic.   

Because there are a number of immunological disorders that result in a susceptibility to similar opportunistic infections that are characteristic of AIDS, PCP had been well studied before AIDS appeared.  When the epidemic began we knew how to diagnose this particular opportunistic infection, we knew how to treat it and we also knew how to prevent it.   

 As early as 1977 it had been well established that PCP could be prevented by an inexpensive medication, yet official recommendations for the use of this and other interventions as prophylactic agents against PCP in people with AIDS did not appear until 1989. 

This long delay is a strange episode in the history of medicine, although it is barely remembered today.   But anyone who experienced the first decade of the epidemic in the US will remember the scourge that was PCP.

Attempts to bring this effective prophylactic measure to attention had been made by individuals in the gay community  well before its formal introduction in 1989, most notably by Michael Callen, an early AIDS activist who has since died. 

First a few words about PCP.  Thanks to antiretroviral medications this infection is now relatively uncommon.  But it most certainly has not gone away.    Although the name of the causative organism has been changed to Pneumocystis jiroveki from Pneumocystis carinii, we still recognize the pneumonia associated with it as PCP.   The organisms interfere with the diffusion of oxygen into the blood, and untreated, the infection is almost always fatal, in effect causing death by suffocation.

To get an idea of the extent of the fatalities this pneumonia caused,   Michael Callen asked a CDC statistician in 1989 how many AIDS related PCP deaths had occurred since the beginning of the epidemic.    As of February 20^th, 1989, 30,534 Americans had died of AIDS-associated PCP.  The year is significant as it was then that the CDC finally issued recommendations for the prevention of PCP, using a drug that had been known to prevent this kind of pneumonia since 1977.

The drug in question is Bactrim, also known as Septra, Septrin or co-trimoxazole. It is actually a combination of two drugs, trimethoprim and sulfamethoxyzole.   It has been available as an inexpensive generic product for many years.

Bactrim was first demonstrated to be an effective prophylactic agent against PCP in children with leukaemia by Walter Hughes in 1977.  What about other immunocompromised conditions associated with a susceptibility to PCP?  Dr Hughes suggested in a 1981 publication that in these other immunocompromised conditions, where a first episode of PCP was known to be followed by a rate of recurrence of about 15%, Bactrim should be prescribed after the first episode.  

In AIDS we soon learned that the rate of recurrence of PCP was about four times higher than the 15% threshold suggested by Walter Hughes as an indication for prophylaxis.   By 1984, if not sooner, we knew that one episode of AIDS -related PCP was followed by another within a year in at least 60% of those initially affected.  I don't know if Walter Hughes made any proposals that PCP prophylaxis in this new disease should be considered differently to his 1981 recommendations regarding the use of bactrim in immunocompromised conditions other than childhood leukaemia.   He was a member of the CDC committee that recommended the use of Bactrim to prevent PCP in AIDS in 1989.

It is true that people with AIDS have a higher frequency of adverse reactions to Bactrim than those not infected with HIV.  These are mostly hypersensitivity reactions including fever and rashes.  But we soon learned that these reactions could be frequently avoided by a desensitizing process, involving a gradual increase in dose.  We also learned that the initial dose proposed by Dr. Hughes in the 1970s and by the CDC committee in 1989, which was two double strength tablets a day, was much higher than needed.  Bactrim given only three times a week is equally effective.

It is worth quoting the following passage from the CDC recommendations.

"In 1989, the United States Public Health Service convened a Task Force of experts to consider the expanding knowledge base about prevention of Pneumocystis carinii pneumonia (PCP) among adults and adolescents (greater than or equal to 13 years of age) with human immunodeficiency virus (HIV) infection. This Task Force concluded that the morbidity, mortality, and cost due to PCP could be substantially reduced by appropriate use of antipneumocystis prophylaxis in subgroups of HIV-infected patients known to be at high risk, and developed recommendations for the administration of prophylactic regimens. "

At this time 30,534 people in the US had already died of PCP.

Michael Callen was a patient of mine.   He was tireless in his advocacy that recommendations be promoted  to use measures to prevent PCP in people with AIDS.    Michael was also one of the authors of the Denver Principles, which in his words essentially state "People with AIDS should have a say in any decision-making process that will  affect our lives".   He tried to do this with respect to PCP prophylaxis. 

Michael with other activists met Dr Fauci in May of 1987, Michael was insistent in asking for recommendations to prevent PCP in people with AIDS.   Michael wrote the following in relation to this meeting:

"It is particularly galling to me that 16,929 of the 30,534 unneccessary PCP deaths occurred since May of 1987, the date on which I and other AIDS activists met with Dr. Anthony Fauci (the closest person we have to an AIDS czar) to ask him - no, to beg him - to issue interim guidelines  urging physicians to prophylax those patients deemed at high risk for PCP.  He steadfastly refused to issue such guidelines. His reason? No data. As a result many more people died of PCP who didn't have to".

Dr Fauci wanted data from a clinical trial of Bactrim for PCP prophylaxis in AIDS before he would recommend its use.  But people were dying of PCP at a terrifying rate; I and some other physicians could not wait for these recommendations.  I was routinely prescribing  Bactrim, or another drug, dapsone to patients  I deemed to be  at risk for PCP.

I was fortunate in that I had some experience in the 1970s  dealing with infections in people who had received kidney transplants. These individuals are intentionally immunosuppressed, to avoid rejection of the transplanted kidney, and because of that immunosuppression, they experience a number of the same opportunistic infections seen in AIDS, including PCP. They also can sometimes get Kaposi's sarcoma.   As an infectious diseases specialist, with some experience in the transplantation field,  I was familiar from the beginning of the epidemic  with the use of Bactrim to prevent PCP. 

I found it  remarkable that at some transplant centers patients received PCP prophylaxis without the need for a trial while people with AIDS were denied this intervention.  There had been several trials of PCP prophylaxis in different transplant populations at various times.  But after  Walter Hughes demonstrated the efficacy of bactrim in 1977, the need for these trials is debatable.   I don't know if anyone has written a history of the use of PCP prophylaxis following Dr Hughes 1977 trial.   I feel fairly certain that in groups at risk for PCP other than the  leukaemic children studied by Dr Hughes, Bactrim use has been erratic, with some receiving the intervention, maybe just following the criteria suggested by Dr Hughes himself  in 1981 (where the PCP  recurrence rate is at least 15%), while other groups had to wait for the results of trials before receiving the benefit.

In the case of AIDS a trial of Bactrim prophylaxis was finally conducted by Margaret Fischl in patients with Kaposi's sarcoma, using two double strength tablets a day.  At this dose adverse reactions were seen, but only 5 (17%) of patients had to discontinue treatment.  As already noted we soon learned how to reduce the frequency of these reactions by desensitization procedures and  using a much reduced dose.

The CDC recommendations did note that the trial was conducted in patients with Kaposi's sarcoma, and in a typically pedantic and ultimately absurd fashion, warned us that there was no evidence that prophylaxis would be effective in AIDS patients without Kaposi 's sarcoma.  They thankfully stopped short of demanding a trial in AIDS patients without Kaposi's sarcoma.

In the early days of the epidemic we could not know which patients were at risk for PCP. We had to learn that 200 CD4 cells was the dangerous threshold, below which there was a substantial risk of infection.    But well before this we were perfectly able to target a population at great risk for PCP: these were people who had experienced one attack already.  They were almost certainly going to experience another one but their protection was not considered to be a matter of urgency by the federal AIDS medical leadership.   Of course in the absence of effective treatments for HIV disease, preventing PCP would have been a life extending rather than a life saving intervention.

Another curious and indefensible objection to PCP prophylaxis was  raised by Dr Samuel Broder who was then head of the National Cancer Institute.  He felt it justifiable to discourage the use of PCP prophylaxis on the grounds that the introduction of AZT would make this practice redundant!    This objection was raised in the complete absence of any evidence that AZT could prevent PCP in a significant and durable fashion, if at all.

Michael Callen promoted PCP prophylaxis in other ways.

He was the President of the PWA Coalition in New York City (PWAC), and the founding editor of the PWA Newsline.  Michael did what he could to bring attention to the need for PCP prophylaxis in the PWA Newsline.    He also did so in two volumes published by PWAC - Surviving and Thriving with AIDS.

    Around 1987 feeling so frustrated at the wilful neglect of  PCP prophylaxis by so much of the medical establishment, I  wrote a one page article for the Newsline.  I remember the occasion quite well as neglect of PCP prophylaxis was something Michael and I  often discussed.  During one of these discussions, out of frustration, I grabbed a piece of paper at my New York apartment and wrote  about PCP prophylaxis for the PWAC  Newsline.  It  probably  took me  less than ten miniutes  with Michael standing behind me .  It was published unchanged.

Here is a reproduction of that article and also a later one, both  for the PWA Newsline.

The road to PCP prophylaxis was already long and troubled, but had one further detour to make, an expensive distraction with aerosolized pentamidine lasting four to five years.    Pentamidine is another  drug  used to treat PCP for years before the AIDS epidemic was first recognized.   In fact, when it was needed  before AIDS began,  it had to be requested from the CDC where the stocks were kept.  One indication that AIDS cases were appearing at the beginning of the 1980s was awareness at CDC that there were increasing numbers of requests for pentamidine, meaning that there were more cases of PCP.    Pentamidine is given by intravenous injection and has significant toxicity.   It was hoped that this toxicity could be avoided by delivering the drug directly to the lungs by aerosol inhalation.    The droplet size was important if the drug was to reach the parts of the lung where the organism proliferated.  So much time was initially spent in studying nebulizers of different design.  Two types competed - an ultrasonic mechanism for delivering droplets and one in which the aerosol was produced by a nebulizer using compressed air.  Then trials of its safety and efficacy were needed. In 1987 two trials were conducted by two community research organizations.  The Community Consortium in San Francisco provided efficacy data, and the Community Research Initiative (CRI) in New York provided the safety data required by the FDA in the approval process. I wrote the protocol and was the principal investigator for the New York study, which was funded by Lyphomed, the company that manufactured pentamidine for aerosol use.   

Pentamidine for injection was available as a generic preparation.   The formulation for aerosol use however was not and so was costly in the US.  Another organization that Michael Callen, Tom Hannan and I had organized to distribute egg lipids - AL721,  (an interesting topic itself, perhaps  for another post)the PWA Health group, imported a cheaper version from the UK.

A number of physicians treating people with AIDS set up inhalation machines in their offices.

Here is what it looked like. The picture was taken during the CRI trial.

Aerosolized pentamidine proved to be inferior to Bactrim as a prophylactic agent  and was associated with unusual complications.  It presented environmental hazards as other organisms -such as TB could be disseminated, and also resulted in the occurrence of pneumocystis infections in organs other than the lungs.

In all likelihood aerosolized pentamidine was pursued as a possible PCP prophylactic agent because interest in Bactrim was so discouraged by the federal medical leadership.  

 It is not irrelevant to note that unlike pentamidine for use as an aerosol,   Bactrim  was available as an inexpensive generic preparation. 

Should there be interest in a longer and referenced account of this curious episode in the medical response to AIDS, which also tries to find some explanation for the long delay in providing patients with a simple life extending intervention the following link will lead to a more detailed article written in 2006. 

2006 article on PCP prophylaxis

I don't think this is the case.  It is not the only example of the success of prevention education.    In a totally different situation, the number of HIV infections in Uganda fell in the 1990s.  This coincided with the introduction of an intensive prevention education initiative.

Of course the characteristics of the epidemic in the US and Uganda are enormously different; the major means of transmission in Uganda is through heterosexual sexual contact and using this example certainly does not mean that those prevention education measures adopted in Uganda would be appropriate in the US.   The example is an illustration that prevention education can work.
 

With these very different examples we can safely say that in principle, HIV prevention education can be effective.

In the US, in the early years of the epidemic, we had the horrible constant reminder of what we were facing in the frequent deaths of our friends and patients, an experience that younger people are now spared, at least on a daily basis.   It seems absolutely reasonable to accept that these terrible reminders of what HIV infection could do contributed to the success of safer sex campaigns.  Of course there are other differences today, not the least of which is that we have the great benefit of the availability of antiviral drugs. 

The disease is viewed in a different way now, from something that seemed to be uniformly fatal to a "chronic manageable disease".  I have put the term in quotes because it is a misleading message put out by many health departments, and the Centers for Disease Control (CDC), as an explanation why HIV tests should be as routine as having your blood pressure taken.  While there is of course  every reason to test for HIV as widely as possible, it's my opinion that comparing HIV disease to conditions like high blood pressure to promote testing  can have a negative effect on prevention education.

Chronic, so called manageable diseases are in fact not all the same. Some are manageable with great difficulty and sometimes for not very long.   The means used to manage the disease may themselves not be free from problems.

HIV disease has, without question, been transformed by the availability of antiviral drugs.  But it still requires lifelong regular medical supervision, adherence to treatment regimens and, for some, dealing with severe adverse responses to the medicines.  Then there is frequent stigmatization, difficulties in finding care, problems with employment, alienation of family, and a multitude of other difficulties that many people with HIV must face.  No, HIV disease is not like having high blood pressure, diabetes or asthma, as the CDC would have one believe.

Despite this, it is possible that the message that HIV disease is now not so serious that is implicit in the reassuring description of the disease as a chronic manageable one, may have lessened the fear of becoming infected in some individuals.  This is also a possible effect of some advertisements for antiviral drugs that suggest that taking them will transform one into a mountain climber.

But these and other obstacles to effective prevention education programs should be taken into account when designing new strategies.  They can be overcome if there is a will and funding to mount large-scale properly targeted prevention education campaigns.

The most effective prevention education efforts can only have a chance of success if they involve the affected communities at every level.   With a  need for highly targeted prevention education material, various community  groups are best able to craft the messages that are best suited to their needs, if given adequate resources.

The first proposal to use condoms in 1982, came from individuals under threat themselves, not from any organization, and certainly not from a government where the President at that time was unable to even mention the word AIDS or later, one who supported abstinence-only programs.  

In 1982, despite the opposition of organized community groups, I with two of my patients, Michael Callen and Richard Berkowitz, were able to disseminate a booklet suggesting the use of condoms.  This endeavour was made possible, not by a foundation or any other organization, but by an individual, Randall Klose who provided the funds.  Few probably remember Randy Klose, but many should know about him and what he made possible.  Even the foundation that I had incorporated, the AIDS Medical Foundation (which became Amfar) found the explicit words of the booklet a danger to fundraising, and refused financial support. They did help however, by providing fiscal sponsorship of Randy's donation.

This was a community triumph.   It arose from affected people themselves, who were not about to wait for some benevolent authority to introduce some way to prevent getting this disease.

When I started this post I pointed to the success of prevention education among groups of gay men in the mid to late 1980s.  I had to say groups because just as cases were declining in white gay men they were increasing in African-American men. 

The neglect of prevention education that is properly targeted to those at risk that is culturally-sensitive and persistently delivered is demonstrated in the most awful way by the current disaster in many African-American communities.  

I, as many of us, have been following demographic trends of the epidemic since its start.  The advance of this disease into African-American communities became quite apparent in the late 1980s, visible to all who cared to look at surveillance data.  By 1993 the percent of diagnoses in African-Americans started to exceed that in white Americans.    Certainly by 1990, we could have had no better evidence to target a group in great need of prevention education, yet "America Responds to AIDS" was the best we could come up with.  For those who did not see this program, it was a vacuous untargeted waste of money and time and an indication of ineptitude or indifference on the part of authorities whose task it was to protect us.

 Take a look at this picture that tells a horrible story that words cannot match.

This represents a tragedy that has been developing in full view for more than twenty years.  We knew as early as 1987, and certainly in 1990, that without intervention a preventable disease would inexorably move into African-American communities.  This picture tells us exactly how America responded to AIDS.

In the light of this evidence, how are we to understand the comments of Dr Fauci , who was appointed as  the AIDS coordinator for the National Institutes of Health in 1985?

In February, 2009 he noted that these "shocking statistics would be tragic anywhere but are particularly inexcusable in a wealthy country such as the United States"

His complete statement can be seen here:

http://www3.niaid.nih.gov/news/newsreleases/2009/BAAID_09.htm
 

But this is only one of endless comments by authorities on a tragedy that was developing before their eyes for twenty years.  The same might be said about the many comments on the dire condition in Washington DC.  

It is not only the federal AIDS leadership that failed to respond to warning signals flashing brightly right in front of them. In the early days of the epidemic there was a vigorous and exemplary community activist response. This was a terrific example of people dealing with a deadly disease taking action on their own behalf, fighting for the best medical and scientific response and against the shameful stigmatization of HIV infected individuals.

The flowering of AIDS activism in the late 1980s and early 1990s achieved a great deal. All people dealing with serious illness have benefitted from the precedent that was set. Yet, in recognizing this achievement, we must also wonder why many of these experienced advocates, who no doubt were aware of the demographic trends shown above, seemed generally less willing to at least try to avert the disaster threatening their fellow citizens? Of course some tried, and maybe were overwhelmed by massive indifference.

Whatever the reasons, the advocacy of US activists abroad, particularly in Southern Africa, proved to be more effective than anything they were able to achieve in their own country for their fellow African American citizens.

There are also other groups where AIDS has been, and continues to be a growing problem, but have been relatively neglected.

To conclude this post I want to explain why HIV prevention education must be closely linked with the promotion of studies on PrEP.

This will also be a response to some comments made following my last post on PrEP, particularly those of Anna Forbes of the Global Campaign for Microbicides  (GCM).  If you click on this link  you will find several papers on ethical issues associated with prevention trials, as well as the links Anna Forbes provided in her response, to in-depth analyses of previous problems in PrEP trials in Cambodia and Cameroon.

I should say that Anna Forbes' presentation at the CHAMP teleconference was extremely good;  she made it quite clear that PrEP was not intended to be a replacement for current recommendations which include the use of condoms.

What I have written above about my involvement with prevention education ever since our booklet "How to have sex in an epidemic: one approach" was written in 1982 should explain the position from which I wrote my last POZ blog post, and why I responded as I did, particularly to the CHAMP flyer.

When I read the flyer I feared that by failing to state that PrEP was not a replacement for current prevention approaches, the interpretation made by some might have been that prevention education is ineffective and that therefore a new prevention strategy was needed.  More people probably saw the flyer or eblasts than participated in the teleconference where the issue was clarified.

It is of course true, as one person stated, that a flyer cannot contain all details. But surely a statement that PrEP is not intended to replace current prevention recommendations including condom use should have been there.

Most of this post has been a defence of HIV prevention education, arguing that it would be quite wrong to conclude that in principle, it is ineffective. The failing has been in the efforts of those responsible for it, a lack of interest or maybe just a belief that the effort would be useless.  As for funding, while the changes shown in the above illustration were steadily progressing in full view, "America Responds to AIDS" was on every TV set in the country.  That must have cost many millions.

As with almost everything in HIV medicine, a one-size-fits-all approach seems to be the norm. It's certainly cheaper to deal with populations rather than customize responses to fit the needs of individuals.  Treatment recommendations are made without concern for individual differences in the rate of disease progression.  At the very least, North America and Europe can afford the expense of individualizing treatment for HIV, as is typical for most other life-threatening conditions.

In the same way there are differences in prevention needs in different communities and differences within these communities. These differences are reflected in differences in what is hoped for from PrEP.

For some women (and some men) PrEP may represent the most practical,  though as yet unproven, way to avoid HIV infection.

For others, both men and women, it may represent an added layer of protection to condom use or other risk reduction measures.

Some may hope that it will provide a safe means to conceive.

Others evidently hope that it may represent a safe way to increase sexual intimacy for people with HIV by dispensing with condoms altogether, although I find it impossible to envisage how safety could ever be tested.

These are all very different situations; the stakeholders are indeed a diverse group. 

Some need PrEP to remain uninfected while others want it, even though there is no insuperable obstacle to following current  HIV prevention recommendations.

The power of men to protect themselves and their partner is the use of a condom.  The only theoretical power available to a woman (apart from the female condom) is the power to say no.  But I say theoretical power, because in real life there are many situations in which this power cannot be exercised. 

It is clear that we need prevention interventions  that are in the control of individuals who are the receptive partners in sexual intercourse.  For these individuals, the study of PrEP is of the greatest importance.

As far as choosing to dispense with condoms is concerned, Swiss investigators have proposed a reasonable set of circumstances when this can be safely done.   These circumstances will apply to very few.  For others where infectivity is realistic, I can think of no way to determine if PrEP would provide a means to safely dispense with condoms.

 Prevention education has been shown to work among men who have sex with men.  And today in America, it is those men--Black, Hispanic, White, Native American, gay men of all ethnicities--who carry the greatest burden of this disease.  So when new strategies are being explored, it is important that it is not even implied that prevention education is  something that cannot work well enough, and therefore new prevention strategies are required. Presenting a new prevention strategy such as PrEP should be accompanied by an encouragement and strengthening of prevention education that we know can be effective. 

As far as my comments on efficacy trials of PrEP are concerned, I believe there is a realistic possibility that a reliable and generalizable result on efficacy may unfortunately be impossible to obtain. There are added, but hopefully not insuperable  potential problems, like  adherence to PrEP and the risk of developing resistance.  Now we also have the troubling news that pre-existing bone density issues among some African men may present a problem in the use of tenofovir as well as growing research indicating the demineralising effect of its long-term use.

It seems better to offer an unproven intervention that has something to support its use, with appropriate testing for infection and toxicity, rather than do nothing. Where conditions permit this, there is a case to be made for presenting this as an informed choice that individuals have every right to make on their own behalf.   This would be the case where, in practice, there is no other intervention available.    In the 1970s I prescribed antibiotics to patients as pre-exposure prophylaxis against gonorrhoea and syphilis, presenting adequate information and follow up testing.  It was a choice I felt they had every right to make.  Despite being chastised by my colleagues, I was able to prevent gonorrhoea and syphilis in some of my patients (of course I have no proof of this, but it is likely that infection was avoided).   HIV infection however is quite a different matter, but still, with full information, making decisions on their own behalf remains the right of an individual.  But we don't yet have full information, and anti-retrovirals are available in many parts of the world.  This is another reason to do what we can to complete efficacy trials of PrEP. 

I certainly had no intention to discourage the study of PrEP; my interest was in strengthening and improving prevention education. This is something that must go hand in hand with the study and promotion of PrEP, not only in trials, where this is happening, but at a community level.