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An unwise recommendation by the WHO.

July 20, 2014 1 comment

 

PrEP is an HIV prevention intervention in which antiviral medications are taken to interrupt sexual transmission of the virus. It is now being recommended by the WHO for, it seems all   sexually active gay men.  Actually it’s not quite that stark – they continue to recommend condom use as well.   Despite this, many will probably see this as a recommendation to rely on PrEP as an alternative to condoms.

 

The WHO recommendation is a population based proposal, a public health recommendation as opposed to recommendations for specific individuals.   Recommendations for individuals are different because they take into account individual circumstances, such as the extent to which a specific person is at risk.  Population based recommendations are recommendations made across the board, in the case of the WHO, addressed to all men who have sex with men.

 

While assuring us that the recommendations are evidence based and providing the customary explanation of how the strength of evidence is graded, we learn that the WHO has made a sweeping worldwide population based recommendation on evidence provided by just one randomized study!    This was the iPrEx study, which was beset with interpretative difficulties, not least because few took the medication as directed, if at all.

 

We simply do not know enough about PrEP to make a sweeping population based recommendation. .  We have little idea of what adherence to the medication might look like in various populations, we know little about the degree of protection in specific sexual acts.  Different sex acts carry different risks, for example, to the receptive or insertive partner in anal sex.   Also, how effective is PrEP  in situations of exposure to high and low viral loads.  In addition we have little idea of the extent to which condom use will be abandoned.

 

It’s clear that there is a widespread view that PrEP is an alternative to condoms, despite official recommendations stating that PrEP  should be part of a comprehensive prevention approach that includes condom use.

 

 

A more balanced response would have been a call for more research, and importantly, for a fuller description of those individual situations where PrEP use is a rational preventative intervention at the present time.

 

 

The use of PrEP by an individual is very different.     The degree of risk to individuals will vary considerably and on an individual basis PrEP use can be a completely appropriate intervention in situations of very high risk, even if we do not have precise information of its efficacy without condom use.   The use of  PrEP could also be considered when there is an inability to maintain an erection with a condom.  It might be an option to enable a fuller sexual expression among what is probably   a large number of men whose difficulty with condoms, for whatever reason,  stands in the way of satisfactory   sex.      Medical supervision is also more likely in individual situations. It is important to check for HIV infection and to monitor for sexually transmitted infections and drug toxicities.

 

 

Monitoring for sexually transmitted infections is important.  Since PrEP alone offers no protection from the transmission of infections that might be interrupted by condoms we might expect an increase in such infections with a wide roll out of PrEP.  The current increase in sexually transmitted infections among gay men in some cities is most likely attributable to an increase in unprotected sex.    Many sexually transmitted infections facilitate the transmission of HIV which may be another factor that could drive an increase in new HIV infections.

 

 

 

The way PrEP has been promoted during the past few years has surely contributed to the poor support received for prevention education.   One way in which this has happened is the shifting of budgets for prevention to those entities, private or government insurers that pay for drugs used in biomedical prevention.

 

There seems to be a widespread view that prevention education does not work.  But we know that it can work. The adoption of safe sex practices including condom use in the early 1980s curbed the spread of the epidemic, although admittedly conditions are not the same today.  There is little support for continued condom use, and rather than take the view that condoms don’t work, we might try to understand the obstacles that stand in the way of effective prevention education.

 

 

 

If prevention education has been ineffective it’s  be because there has been so little of it, and what little there is has not been properly targeted.  The move of the epidemic into African American communities during the 1990s  was occurring in plain view yet the federal government was churning out expensive vacuous untargeted prevention messages in the form of “America responds to AIDS,” a futile exercise that helped to discredit prevention education.

I get the sense that some younger gay men feel they have missed out in not experiencing the abandon of the 1970s and see PrEP as a way to make up for this.  The real lesson of the 1970s is that sex with multiple different partners on such a vast scale, as occurred in NYC in the 1970s, permits any pathogen that can be transmitted sexually to disseminate widely. That’s what started to happen with amebas and other intestinal parasites and HIV, and is happening with syphilis, gonorrhoea, herpes, hepatitis and many other infections.  There surely will be others beyond HIV.

 

Since we really have very little information about PrEP, and almost none about its use on a population level  such a broad recommendation by the WHO is absolutely inappropriate, so maybe  faced with increasing HIV  infections among gay men,  the WHO is simply giving up  and proposing an unproved intervention out of desperation.  When I say unproven, I mean it is unproven as a viable population based intervention.    Looked at this way, it’s a put down –  a response that may be no more than gestural to people who continue to harm themselves by refusing to use condoms in sex with partners of unknown sero status.

 

This unwise WHO recommendation may also have the effect of increasing new HIV infections if it results in an increase in unprotected sex where adherence is inadequate.

 

I hope there will be a critical look at the WHO panel and funders responsible for producing such unhelpful recommendations.

 

 

 

 

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The Cost of Truvada Pre-exposure prophylaxis, PrEP

August 17, 2011 1 comment

In my last post I wrote about the very small reduction in the absolute risk of HIV infection in the iPrEx trial among those taking Truvada  as pre-exposure prophylaxis.

The 44% reduction in relative risk conferred by Truvada was the only efficacy measurement explicitly presented by the investigators.  That the absolute risk reduction was only 2.3% was not mentioned in the various presentations.

I suspect that many reading press reports of this so called breakthrough were unaware that in fact, the actual risk to people taking Truvada was 2.8%.  (36 infections in 1251 participants).  True, this is less than the 5.1% risk to those on placebo, but by very little.  Certainly not enough to justify the bewildering acclaim given to the iPrEx trial results.

Failing to clearly state the absolute risk reduction of an intervention is something we have come to expect from salesmen to inflate the efficacy of a product, but not from clinical researchers.  Large reductions in relative risk can be associated with minute reductions in absolute risk when the events prevented are low to begin with.

Another important reason why absolute risk reduction should be stated in a report is that this allows one to calculate the number of people who need to be treated to prevent one event, in this case, one HIV infection.

Although the iPrEx investigators did not explicitly provide these numbers, they can be worked out from data presented, as I did in my last post and was also done in a letter published in the New England Journal of Medicine of April 7, 2011 in response to the iPrEx trial report, where the authors report that 44 people need to be treated to prevent one infection (I got 45).

They then went on to calculate that it would cost $400,000 a year to prevent a single infection.

This figure does not even include the cost of the necessary monitoring for infection.  In another letter, it was suggested that such monitoring be done monthly to prevent the emergence of resistant virus by detecting infection early.

From Sean Strub’s calculations (in his comment to my post on the POZ magazine website) which included doctor’s visits and tests, the annual cost to prevent a single infection  would be about $500.000.

These figures are based on drug costs in the US.

Truvada PreP not only does not work well enough it will cost a half million dollars a year to prevent a single infection.

Maybe this is indeed a “game changer” but not in the sense intended by the triumphalist reports coming from the recent Rome AIDS conference.

There definitely seems to be a perception that PrEP is a viable prevention option for everybody; there even have been calls for its general implementation.  These cost estimates alone would make it unfeasible as a public health measure but there are additional reasons, importantly its relatively low efficacy.

PrEP is a reasonable option for only a very  small number of individuals at high risk for infection who are able to be regularly checked for infection.  I believe there is no disagreement about this; the controversy is only about its general use.

Implementation of PrEP on a wide scale will almost certainly result in an increase in new infections.  It’s not only adherence to the drug regimen that will not be maintained by all.  Adherence to a schedule of regular testing for infection cannot be relied on. Facilities for performing the needed tests may not even always be available.

The way PrEP has been promoted has probably already damaged targeted prevention education programs with support for continued condom use, an activity already in great need of support.

Drugs for prevention are paid for from a different budget than prevention education programs, and health departments already under budgetary constraints may feel that prevention needs can now be paid for by those entities that pay for drugs, private insurers or Medicaid/Medicare.

The amount of almost uniformly uncritical publicity given to PrEP is completely out of proportion to its utility.  It’s a hugely expensive and very poorly effective prevention intervention, of use to only a very small number of individuals, and its misleading promotion has probably already damaged prevention education programs.

Considerable resources must have been devoted to publicize and promote PrEP over many years,  in a way that has not taken care to reinforce prevention education with support for continued condom use.    One can only wonder why.

Drs Dong Heun Lee, M.D.  and Ole Vielemeyer, M.D of Drexel University College of Medicine in Philadelphia are the authors cited.

Pre-exposure prophylaxis with Truvada just does not work nearly well enough.

August 6, 2011 2 comments

Pre-exposure prophylaxis (PrEP) to prevent HIV infection  with Truvada  is not sufficiently effective

 

 

There is a similar
post on the POZ magazine website.

PrEP is a prophylactic intervention where uninfected people take anti HIV medications before sexual intercourse to prevent becoming infected with HIV. The use of a vaginal gel containing an anti HIV drug has also been tested.

The results of several trials of PrEP have been reported in the past year, all but one hailed as huge successes, with reported efficacies of up to 90% among those adhering to the treatment regimen.

The efficacy of PrEP in preventing HIV infection was so great that this intervention has been trumpeted as signalling a revolution in HIV prevention.  A new era has opened up we are told; PrEP is a “game changer”.

With such enthusiastic coverage it may come as a surprise that none of the reports explicitly told us what the actual efficacies of the interventions were in preventing HIV infection, perhaps because they were so low as I’ll describe.

Maybe what’s even more startling is that this omission seems to have gone completely unnoticed, at least in the universally jubilant press reports and equally enthusiastic press releases from AIDS advocacy organizations.

How has this been possible?

The reason is that the results have been reported as reductions in relative risk only.   This tells you nothing about actual risk reduction.  What is reported is a percentage reduction in risk from a number that was never clearly stated.  For example in the iPrEx trial of PrEP among men who have sex with men, the drug, Truvada, was reported to reduce the risk of infection by 44%.  But 44% of what?  We were not explicitly told, although it’s possible to calculate what it is.

In fact we can calculate that the absolute risk reduction conferred by Truvada is a measly 2.3%, a number nowhere to found in the trial report.

The relative risk reduction may have been 44%, but this translates into only an actual 2.3% reduction in absolute  risk, as is shown below.

Reporting relative risk reduction only is the oldest trick in the book to exaggerate the effects of an intervention, used by salesmen, but apparently also by clinical researchers.

What makes the unquestioning acceptance of these reports of relative risk reductions achieved by PrEP even more remarkable is that there is a tremendous amount of material explaining the difference between relative and absolute risk reduction.   Just type the words “relative risk absolute risk” into the Google search box.

Relative risk reduction tells you the percentage reduction in risk in the treated group compared to that in the group receiving placebo, or how much lower the risk with the intervention is relative to the risk to begin with.

If you are not clearly told what the risk is to begin with, then you can’t tell what the actual reduction in risk is when taking the intervention; all you know is how much lower it is than a number that’s not clearly presented to you.

Although not included in the iPrEx trial report there is information that allows one to calculate the absolute risk reduction conferred by Truvada.  To do this we need to know what the risk of infection is to begin with.

This is the number of infections occurring in the placebo group over the time period of the study.

64 out of 1248 people in the placebo group were infected, which is 5.1%, or 0.051 in 1.  (since then there have been additional infections reported at the Rome AIDS conference, reflecting an increase in the number of infections over a longer time period).

In the group receiving Truvada 2.8% of 1251 people were infected.

The absolute risk reduction conferred by Truvada is simply 5.1 minus 2.8 which is 2.3.

A 2.3% reduction in absolute risk conferred by Truvada is the more accurate measure of its efficacy.    Hardly something to celebrate.

A 44% reduction in relative risk sounds much better, although far from spectacular,but unfortunately this number tells you nothing about actual risk reduction.

Relative risk reduction is calculated as follows:

It is the number of events in the treatment group subtracted from the number of events in the placebo group divided by the number of events in the placebo group.

On its own, relative risk reduction is not a helpful number.

Of much greater help to a person considering Truvada PrEP is knowledge of the actual risk while taking Truvada (over the period of the study, a median of 1.2 years).

That number is 2.8%.

Knowing the absolute risk reduction allows one to calculate another important measure.  This is the number of people who need to be treated to avoid one infection (NNT).
From information contained in the trial report 45 people need to be treated to prevent one infection.  I did not notice this number in the trial report nor was the absolute risk reduction
of 2.3% reported.   NNT is a useful number as it allows one to estimate what it would cost to prevent a single infection with Truvada.

The cost of the drug is the least of it.  A person taking Truvada PrEP needs to be monitored at regular intervals for toxicity and importantly, for infection, in order to avoid the inevitable emergence of resistant viruses as a result of sub optimal treatment.

If Prep is implemented on a large scale which some AIDS advocates seem to be calling for, but is unlikely to happen, then there may well be increases in new infections with viruses resistant to the drugs in Truvada  in men who have sex with men, in IV drug users and in African populations.

PrEP is not a success, at least not with Truvada.

However such a failure was transformed into a triumph, part of the explanation is the use of relative risk reduction numbers with care taken to remain silent on absolute risk reduction.

Despite all the literature available to help people tell the difference between absolute and relative risk reduction, this evidently was a resource not used by those cheering along  this ineffective intervention.

HIV Prevention Education and Pre-Exposure Prophylaxis Against HIV. August 2009

August 30, 2009 Leave a comment

Since my last post on this subject I have heard a variety of different views as well as discussed the issue with several  interested individuals.

As a result I have come to see the issue somewhat differently; I suppose I could just amend my last post, but it’s better to leave it as it is and  describe the differences in how I now view PrEP efficacy trials after having heard several different descriptions of  ways in which these are seen.

I listened to presentations at two conferences during the  last few weeks.  A teleconference organized by CHAMP, a community group, and one organized by the Centers for Disease Control (CDC).  These conferences attempted to engage and inform individuals about PrEP.       As a consequence I realize that I was mistaken in stating so categorically that efficacy trials of PrEP,  unlike safety trials, could not be undertaken in human research subjects.   However I do not think that if all the ethical requirements are met, that is to provide condoms, consistent counseling and sterile injecting equipment, a generalizable result will be obtained indicating that it is an effective prevention strategy.  Of course I don’t know this, and was wrong in my view that trials of PrEP efficacy should not proceed.

The most important concern with the way the promotion of PrEP, at least as a concept, is being pursued is the neglect of encouraging  prevention education.

Prevention education remains the most important tool we actually have, as opposed to theoretical and unproven approaches.  The latter include PrEP, and the test and treat every infected person proposal.   We absolutely know that in principle prevention education, including the use of condoms can work.   It worked in curbing the increase in the epidemic among gay men in the late 1980s .

The principle is thus established, admittedly without application to those who have no control over the use of condoms by the male partner.  This group is therefore in need of prevention strategies they can control themselves, and PrEP may be the only realistic possibility.

For everyone else, the sexual transmission of HIV can be controlled by the use of condoms, even if not with 100% efficacy.  We have a powerful tool in our hands, and if there are new infections, this is certainly not an indication that it does not work well enough.   It indicates that it is an activity that receives insufficient support, or  it may well be that some of those doing it are just not very good at it.  Maybe there is little societal support for HIV prevention education, even little support from individuals at risk who could use condoms but would like not to.

Unfortunately, from what I have experienced, the several groups supporting and promoting PrEP seemed to have given little thought to prevention education in presenting this intervention to stakeholders. .  They may be diligent in the context of efficacy trials, in ensuring the availability of condoms and counselling to participants.

But what seems to be missed is this:  Unless the promotion of PrEP is accompanied by very clear advocacy of prevention education with condom use,  PrEP can be seen as an alternative to safer sex practices as now recommended.

This cannot be the intention, but from comments I have heard after the CHAMP and CDC conferences this seems to be a dangerous conclusion that some have drawn.

The explanation of the utility of PrEP must be accompanied by a strengthening of prevention education to avoid this unfortunate misinterpretation. The very promotion of the concept of PrEP in the way it has so far been done can actually be seen as an undermining of condom use.  A possible alternative to condoms is presented. One can only hope that in the absence of accompanying prevention education there will not be instances sex with available antiretroviral drugs rather than with condoms.

Prevention education is in a dismal state as it is, and we should be aware of any activity that can undermine it further, unless care is taken in how it is presented.

I have commented in other posts that in HIV medicine a one-size-fits-all approach seems to be the norm.  Admittedly it’s cheaper to deal with populations rather than individuals. A single size that fits everybody is even cheaper  than providing  small, medium or large varieties, let alone customizing the size to fit individual needs.

So in HIV medicine, treatment recommendations have been made for all infected individuals, without considering the rate of disease progression, and many other characteristics applicable to any given person.

So it is with PrEP.  Its relevance is different to different constituencies.

At one extreme, for those who have no power to control the use of a condom by their male partner, PrEP may be the only realistic possibility of avoiding infection with HIV.  PrEP to these individuals is obviously of vital importance.

In fact it is so important that it would be useful even if its efficacy, if this can be demonstrated, proves to be inferior to the consistent use of condoms.   Such individuals have no alternative.

The situation of people who are perfectly capable of consistent condom use is different.

The power of the receptive partner in this case is the power to say no. No condom, no sex.   Both partners have an effective means of preventing the sexual transmission of HIV.  There is no need for PrEP to prevent infection, except that some may welcome an additional layer of protection.

There are others whose hopes for PrEP are different.  The desire to conceive is one.

Yet others hope that PrEP will make sex without condoms safe with respect to HIV transmission.   In this case the efficacy of PrEP would have to be known to be at least equal to the consistent use of condoms (and free from toxicity and affordable).   Of course  individuals decide to take risks that involve danger to  themselves only, but full information should be available, and certainly we should take care not to disseminate material that can  mislead, even if only by implication.   We do not have full information on the efficacy of PrEP, and I can see no way of testing its efficacy without the use of condoms.   But it is here that we need to take great care not to mislead, even by implication, that PrEP is as safe as using condoms unless in the unlikely event, it is actually  proven to be so.

Even a modest degree of efficacy is better than nothing for those who are unable to avoid sex with a partner who cannot be relied on to use a condom. There actually is nothing else to protect them.

A modest degree of efficacy is insufficient for those who are well able to refuse to have sex if a condom is not used.   That’s my opinion, and I would believe that of many others, but as  always risking  harm to oneself only,  is an individual choice;  our obligation is not to mislead, and ensure  that full and accurate information is available.

So, PrEP is of undoubted importance to individuals who have no control over the use of a condom by their male partner.  Apart from the female condom, it is the insertive partner who has to use a condom.  All the receptive partner has as protection now,  is the ability to just say no.  We recognize that there are situations when this is not possible, and no practical remedy is available to change this.

Of course there are other situations when it is possible to attempt a change.  If an individual just cannot say no to a partner who cannot be relied on to use a condom because he or she is ignorant of safer sex practices this is something we must try to remedy with intensive prevention education.  This will include imparting the knowledge of the lapses in judgement that can accompany the use of drugs or alcohol.

Getting away from the one-size-fits-all approach, there probably will be some individual situations in which PrEP, even if less effective than consistent condom use may be considered.  An example noted by one commentator is when condom use may be associated with sexual dysfunction.

Prevention education with consistent condom use is the best available means we have to prevent the transmission of HIV.   Prevention education should be strengthened and care taken not to undermine it.

Where individuals have no control over the use of a condom by their male partners  we should do what we can to provide them with the means to protect themselves, and PrEP may be all we have to work on at present.

Others may look to PrEP as a means to avoid the use of condoms.  The price of failure seems to be an extraordinary high one, considering that condom use is known to be highly effective in preventing HIV transmission.

There are people who need PrEP. There are also people perfectly able to use condoms but who want PrEP.

In promoting PrEP studies we must take great care not to undermine efforts at prevention education, even by implication.  Promotion of PrEP must go hand in hand with promotion of HIV prevention education.

PrEP: Pre exposure prophylaxis to prevent HIV infection. August 2009

August 11, 2009 Leave a comment

Pre exposure prophylaxis in relation to HIV infection refers to the administration of anti HIV medications to uninfected people as a means of protecting them from becoming infected with HIV.     It is not known if this intervention will succeed in achieving its goal.   Several trials have been underway to test it for safety and efficacy, and many more are planned worldwide.

I have paid little attention to these initiatives but was prompted to do so by notices of a meeting to discuss pre exposure prophylaxis – now known as PrEP – in the coming weeks.   The wording of this notice is quite vague, but the notice suggests that it is urgent to start planning for the implementation of PrEP as the analysis of initial safety and efficacy trials are expected within the next year.

This is quite startling in its implication that PrEP actually works and presumably is safe.  The actual words of the notice are:

“Results and analyses of initial safety and efficacy trials are expected within the next year, which highlights the urgency to beginning to plan now for how PrEP might be used to maximize its public health impact”.

This is a convoluted statement, to the point of being quite unintelligible. It can be misleading in the implication that can easily be drawn from it that PrEP works. Why else begin to plan for how to use it?

I had not been aware of just how extensive the PrEP initiative has been.   To get some idea of the many trials that are underway or planned, take a look at this website:

http://www.prepwatch.org/

Trials are sponsored by several organizations, mainly it seems, Family Health International (FHI).

http://www.fhi.org/en/Topics/preexposure_prophylaxis.htm

FHI has produced a set of slides listing PrEP trials.

http://www.prepwatch.org/pdf/Meetings/Cates_TDF_slides_May.2006.pdf

Among the “research consortia” listed as involved in PrEP research are the Bill and Melinda Gates Foundation, Gilead Sciences, the Centers for Disease Control (CDC), The National Institutes of Health (NIH),  and UCSF. These trials are conducted  in many countries, including Peru, Botswana, Thailand, the US and Malawi.

Organizations listed under “community consortia” are GMHC,  AVAC, Global Campaign for Microbicides, CHAMP, and the IAS.

The websites of these organizations contain information about PrEP.

AVAC :   http://www.avac.org/

Global Campaign for Microbicides:  http://www.global-campaign.org/

CHAMP:  http://www.champnetwork.org/about

The International AIDS Society:  www.iasociety.org

All the trials use a once daily drug, tenofovir, with or without emtricitabine (FTC). Tenofovir is manufactured by Gilead in the US although I believe a generic version is produced in India.

The trials vary in design.   Some require daily tenofovir, some are used intermittently or specifically before sexual intercourse. Some use a gel formulation.

Previous trials had run into difficulties; several were stopped for different reasons.  For example a trial in Cameroon was stopped amid allegations that those who seroconverted did not receive adequate treatment.  A trial in Nigeria was stopped because of inadequate standards in laboratory testing.

A trial of PrEP among Cambodian sex workers was stopped in 2004 by the Cambodian government.  This was perhaps the most publicized of the several PrEP trials that were stopped, because several activist groups brought attention to it at the XV International AIDS Conference in Bakgkok.   Among the many reasons stated for pressure by activist groups to stop the trial were poor HIV prevention counselling, and a lack of medical services to those who seroconverted.    Act Up-Paris was active in stopping PrEP trials both in Cambodia and Cameroon, although it is reported that this organization is supportive of tenofovir trials in general.

These events are described in an article entitled “The Abandoned Trials of Pre-Exposure Prophylaxis for HIV: What Went Wrong?”  The authors are Jerome Singh and Edward Mills.  It can be seen here.

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0020234

For reasons I will describe I do believe that there is no way to design a trial of the efficacy of PrEP that can meet acceptable ethical standards.   On the other hand, it is perfectly possible to conduct trials to determine the safety of tenofovir for pre exposure prophylaxis.

So maybe an answer to Drs Singh and Mills as to what went wrong with the abandoned trials of pre exposure prophylaxis is that the question of efficacy, unlike that of safety, cannot and should not be tested on human research subjects.

Here are the reasons why this cannot be done, at least regarding the use of tenofovir to prevent sexual transmission of HIV.

No ethically designed and conducted trial can definitely prove that PrEP works.  Definite proof of course may be an unattainable goal, but even credible evidence regarding efficacy  would not be found if the trial were to be conducted in an ethical manner, simply because with the availability of condoms, and the imperative to provide counselling  that they be consistently  used,  such  a trial could not answer the question asked of it. This is essentially because the consistent use of condoms will ensure that insufficient seroconversions occur in participants receiving  placebo.

In any trial that studies the ability of a new intervention to prevent sexual  transmission of HIV, participants must receive persistent counselling about the need to use condoms.  These must be provided, with ongoing support for their continued use.  This is the ethical requirement.

Quite clearly if great care is taken to meet this requirement there will be few infections in people receiving placebo.  The investigators are presented with a conflict of interest that no amount of verbal assurance can resolve.  The conflict is that on the one hand the investigator must always be cognisant of the importance of doing all that’s possible to encourage condom use to prevent the sexual transmission of HIV infection, and on the other hand the investigator has an interest in demonstrating an effect of PrEP in preventing it.

It is only when condom use falls below a certain level that the effect of another preventative measure can be assessed.  We are obliged to do all we can to ensure that this does not happen.

The Centers for Disease Control (CDC) are sponsoring several trials of PrEP[i].  They are very sensitive to the need to provide risk reduction counselling to participants.

Here is an excerpt from material published by CDC:

“One of the greatest risks, as efforts progress to identify new biomedical prevention approaches, is that individuals at risk will reduce their use of existing HIV prevention strategies. It will therefore be crucial to reinforce proven behavioral prevention strategies, both within and beyond these trials. All three trials are taking multiple steps to address this issue during the education and enrolment of trial participants and through ongoing participant counselling.

First, it is critical to ensure that participants understand that trial participation may not protect them from HIV infection—either because they may receive a placebo or because they may receive a study drug, the efficacy of which remains unproven. This and other key aspects of the trial, including the potential risks and benefits of participation, are explained to potential volunteers in the language of their choice, prior to their enrolment. To ensure participants fully understand all aspects of their participation, all volunteers are required to pass a comprehension test prior to providing written informed consent. Study participants are also free to withdraw from the trial at any time and for any reason”.

So there is clear recognition that there may be a falling off in the use of proven prevention approaches, importantly, the use of condoms.

Here is another excerpt:

“To assist participants in eliminating or reducing HIV risk behaviours, extensive counselling is provided at each study visit, and more often if needed. This interactive counselling has proven effective in reducing the risk of HIV and other STDs in multiple populations, including past participants of similar HIV prevention trials. Participants are also offered free condoms and STD testing and treatment to reduce their risk for HIV infection”.

If such counselling is effective, the prevention of sexual transmission of HIV particularly through the consistent use of condoms will make it impossible to detect an effect of PrEP.   As mentioned the investigators are presented with a conflict that it is not possible to resolve.

PrEP is an experimental approach to prevention, while consistent condom use is an established method to substantially reduce the sexual transmission of HIV.

The argument that may be presented by those who are proponents of PrEP is that condom use is not consistent, and that we need an alternative

The implication of such an argument supporting PrEP is that prevention education, essentially the use of condoms, has not been sufficiently effective.  This cannot be known to be true of prevention education in principle.

What is definitely true is that those responsible for prevention education have not been sufficiently effective.

Our efforts  should be focussed on improving prevention education and support for the consistent use of condoms,

There is so much more that can be done with persistent, culturally sensitive, highly targeted prevention education.  In order to improve our efforts at prevention education we have to first confront the fact that we may have not been too successful in this endeavour, understand why,  and absolutely not take the position that the undertaking is an impossible one.

Every new infection today represents a failure, not of prevention education as an undertaking, but a failure to provide it effectively.  The introduction of condom use among gay men in the US in the 1980s originated in this community, it was promoted and effectively advocated for by this community and proved to be effective..   In those early years there was certainly no help from the Government which was to spend enormous sums on a vacuous and ineffective untargeted campaign “ America responds to AIDS” which did absolutely  nothing to stop the advance of this disease into African American communities , although this was happening in plain sight.

What we can learn from this is that different affected communities are best able to understand the  issues specific to their communities that must be emphasized  and  promote prevention education that is most effective for each of them. Their input is therefore  absolutely vital.

The design and implementation of well funded and highly targeted prevention education has been neglected.   These initiatives need to be specifically targeted to different groups, the needs of which must be assessed,  barriers identified, continuing support provided, as well as some instrument developed to evaluate the success of the programs. .   It is an enormous challenge.

We know that gay men were able to make it work for them before the concept of risk reduction had even been articulated. It can work and this is where our efforts must be concentrated.  Not on trials of the efficacy of PrEP that are impossible to conduct in an ethical fashion.

However It is entirely possible  that PrEP may add an additional layer of safety to condom use during sexual intercourse.  This may be of  particular importance in certain circumstances such as among sex workers.  This is also the case among some women who are unable to rely on the use of a condom by their male partners.   Trials of the safety of once daily tenofovir are absolutely possible and even desirable.  Such trials would be unburdened with the ethical problems that make efficacy trials impossible to conduct.  It will be clear that the trials are to determine the safety of tenofovir when used with condoms to provide an additional level of safety.   It is true that we may never be able to firmly establish its efficacy, but if it proves to be safe, there is sufficient – if far from conclusive evidence to justify its use.

It is clear that all that has been written about concerns the sexual transmission of HIV.    For those in whom the risk of infection  is through intravenous drug use there is an entirely different set of considerations.  The only known prophylactic measure, the reliable provision of sterile injecting equipment is probably just unavailable for most, and efficacy trials are therefore not burdened with the same ethical constraints.

One cannot help but note that at least  in two initiatives, pharmacological rather than behavioural approaches to prevention are now being emphasized.  Of course PrEP to prevent  transmission of HIV is one. The other is the attempt to end the HIV epidemic by testing and treating all HIV infected people, whether or not a particular infected individual needs treatment for his or her benefit.  Both are beset with ethical problems.

The use of condoms can significantly reduce the sexual transmission of HIV.  We know this.   Therefore  our greatest efforts should be placed in improving prevention education.  It is a tremendous challenge given the cultural diversity of the populations involved, and the special difficulties experienced by some. This is particularly true where women are disempowered.

We know that untargeted efforts such as “America Responds to AIDS” do not work.  We need to understand the barriers to effective prevention education.

A denial of  the importance of sexual expression to the human experience, stigmatization of those infected, homophobia, racism, bigotry in general and the fact that unlike the use of drugs, prevention education provides no financial return,  are surely amongst them.


[i] [i]    http://www.cdc.gov/hiv/prep/resources/factsheets/index.htm