Comments and discussion on issues in aidsperspective.net as well as on contemporary AIDS issues
RSS icon Home icon
  • iPrEx trial results of preexposure prophylaxis – PrEP

    Posted on December 12th, 2010 admin No comments

    Full Contents of this blog

    Pre-Exposure prophylaxis –  PrEP –  iPrEx  trial results.

    Pre-exposure prophylaxis, or PrEP, is an HIV prevention intervention in which anti-HIV drugs are taken to prevent infection.    A safe, effective and affordable drug that could achieve this would be a powerful prevention intervention even possibly capable of halting the spread of the epidemic.

    Last week we were told the results of the iPrEx trial that tested the efficacy of PrEP with Truvada, a combination of two anti-HIV drugs, in reducing new HIV infections among a group of men who have sex with men considered to be at high risk for HIV infection.

    The announcement of the results was greeted with almost universal jubilation.

    “That’s huge,”  said a prominent AIDS researcher,  “That says it all for me.”

    “Today marks a major step forward in our quest to combat HIV among MSM

    “This discovery alters the HIV prevention landscape forever,”

    “….. the new data “represents the most promising development in HIV/AIDS since the introduction of triple combination drug therapy in 1996.”

    “This is a game-changing trial result,”

    Science magazine reported that..

    “The researchers applauded and some even cried when they heard the bottom line”; “I have not cried this hard in years” – said one researcher.

    These exultant cheers are usually reserved for the most momentous of breakthroughs.

    Demonstrating that a drug could be safe and effective in preventing infection would indeed be a momentous breakthrough as already noted.

    But the iPrEx results, far from representing such a breakthrough, indicated that PrEP,  at least with Truvada, together with counselling and provision of condoms, reduced new HIV infections among men who have sex with men only modestly.   It’s unlikely that the 44% reduction in new infections that was seen is of sufficient magnitude to make PrEP with Truvada viable as a public health prevention intervention. Moreover, as will be described there are significant safety concerns, a demonstrated danger of the emergence of drug resistant HIV, and the drug is far from affordable.

    A 44% reduction in new infections is not huge; even those extolling the trial results would agree (at least I think they would, but who knows considering the over-the-top responses).

    But what is most troubling is that the researchers have squeezed an efficacy of Truvada  of over 90%  by a questionable statistical sleight of hand,  an improper use of sub-group analysis, a technique of data dredging has been soundly discredited.  I’ll return to this.

    This has resulted in  headlines such as “PrEP works – if you take your pills”, I don’t know if this will persuade some people to abandon condoms and religiously take their pills.  Unfortunately the type of analysis that provides confidence to do so is not reliable.  Maybe consistent use of Truvada will reduce new infections by over 90%. Maybe not.

    For the moment staying with the ability to reduce new infections by 44%, as a public health intervention to be used on a wide scale, this degree of efficacy is just not good enough to justify using Truvada to prevent a life threatening infection.   Even if the risk of infection is low this must be balanced against the gravity of the infection. About 3% of participants in the Truvada arm of the trial became infected as opposed to about 5% among those receiving placebo.

    Perhaps it’s on this issue that I’m at odds with the huge acclaim given to the trial results.  Maybe the prevailing view is that a 44% reduction in new infections is indeed good enough; some commentators are even discussing implementation.

    PreP proponents like to compare it to malaria prophylaxis.  If the efficacy of malaria prophylaxis were of the same order as that of Truvada in relation to HIV, I suspect many people might think twice before visiting an area where there was a risk of malaria.

    Let’s take a closer look at the trial results, particularly the claimed greater degree of efficacy in compliant participants   reported in the New England Journal of medicine.

    I have commented briefly on this in my blog on the POZ magazine website.

    The medication used in the trial,   Truvada,  is a combination of two HIV anti-HIV drugs, FTC and tenofovir.  It was compared with placebo in over 2000 men who have sex with men, considered to be at high risk for HIV infection.

    The 44% reduction in new infections was achieved in conjunction with counselling, provision of condoms and monthly tests to monitor for infection.

    This is not a good enough performance to justify widespread use of Truvada to protect against infection.  The investigators then looked at blood and tissue levels of the drugs in people who became infected and those who did not.  They found that those who remained uninfected had detectable drug levels while those who became infected did not.

    They incautiously trumpeted this result as proving that Truvada works well if the pills are taken consistently – stating that in those who took their pills more consistently the relative risk reduction was well over 90%.

    On the surface this sounds good. Almost all the commentators thought so.

    However looking at the results in a sub-group of participants can be misleading.  Most particularly in a sub-group that is defined after randomization; who would or would  not comply with treatment could not have been known.    The problems with subgroup analyses will be clearer after a short account of intention to treat analysis.

    Intention to treat analysis is the most reliable way to analyse clinical trial data.   In such an analysis participants are analysed in the group to which they were randomized, irrespective of whether they dropped out, or didn’t adhere to the treatment or strayed from the protocol in other ways. This seems counter-intuitive, but there are sound reasons why intention to treat is regarded as the best way to analyse trial data, among them  that it more reliably reflects what happens in real life, rather than in a clinical trial.  For example, one reason why pills may not work is because they are not taken. If they are not taken in a trial we have to be concerned that they may not be taken in real life.  Take a look at this excellent explanation of intention to treat:  Making sense of intention to treat.

    As noted, the trial investigators made a lot of the sub-group analysis showing greater efficacy in those who took  Truvada pills as measured by finding the drugs in blood and tissue samples.

    This is surprising  as the pitfalls inherent in such post-hoc sub-group analyses have been recognized for years.  Commentators, some of whom are clinical researchers, in their over-the-top exultation at the results of the analysis in those compliant with Truvada  may have forgotten about the treachery inherent in sub group analysis.  A few commentators give the problem only passing acknowledgement.

    This is a classic paper on sub group analysis:

    Yusuf S, Wittes J, Probstfield J, Tyroler HA: Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials.

    Journal of the American Medical Association 1991 , 266:93-98

    This is from that paper:

    “Analysis of improper subgroups, though seductive, can be extremely misleading, because a particular treatment effect may influence classification to the subgroup. Thus, an apparent subgroup effect may not be a true effect of treatment but rather the result of inherent characteristics of patients that led to a particular response or to the development of side effects”.

    In iPrEx  the subgroups were categorized by events that happened after randomization, so the adherent group is an “improper” subgroup.  “Subgroups of clinical trial subjects identified by baseline characteristics … is a proper subgroup while a subgroup determined by post randomization events or measures is an improper subgroup”.

    In actuality the attention given to the subgroup that had blood and tissue drug levels is an example of the treachery of such sub-group analyses.

    As an illustration, the reduction in new infections seen in this group may well have resulted from the following possibility.

    People who take their pills consistently are more likely to use condoms consistently and in general are more attentive to risk.   So if it were possible to do a subgroup analysis of people who adhered to placebo we might conclude that the placebo also works – (and it’s cheaper).

    This is not so fanciful.

    “In one study [3], those who adhered to the trial drug (clofibrate) had reduced

    mortality; but those who adhered to the placebo pill had the same reduction in mortality”.

    This is from:

    Coronary Drug Project Research Group. Influence of adherence to treatment

    and response of cholesterol on mortality in the coronary drug

    project. Engl J Med 1980;303:1038-1041

    A classic example of the pitfalls of subgroup analysis is  what it demonstrated in the ISIS-2, a trial examining the effects of aspirin after myocardial infarction.  A subgroup analysis showed it was of benefit to all except in people who were either Libras or Geminis.

    Maybe Truvada taken consistently can reduce new infections by over 90%; maybe not.  There was no basis for the investigators and commentators to present the first possibility with such overwhelming confidence.

    We must accept that a 44% reduction in new infections is at this time the most reliable estimate of Truvada’s efficacy as PrEP.   Although, the confidence interval , a measure of reliability, was wide.

    We have an intervention that can reduce new infections by 44%, if taken in conjunction with a program of counselling, condom use, and monthly tests for HIV infection.  That is the benefit.   What about the down side?

    The two most important are the development of resistance of HIV to the component drugs of Truvada and the toxicity of the drugs.

    The utility in treating HIV infection of FTC and tenofovir – Truvada’s component drugs is lost if the virus becomes resistant to the drugs.  Moreover, some mutations conferring resistance to these drugs can also affect sensitivity to some other drugs.  The danger of resistance, and even cross resistance to other drugs developing when Truvada is used as PrEP is not a trivial concern.    Truvada used as PrEP provides a suboptimal dose in treating established HIV infections.  This is precisely the situation in which resistance is likely to develop.   There were in fact two instances of developed resistance in the iPrEx trial in individuals who became infected, but undetected before the trial began.

    Resistant viruses in the community are a danger to all, so the risk of generating resistance is not confined to the individual taking Truvada as PrEP.

    What about safety?

    The claim in many reports that Truvada is without significant toxicity is also misleading.

    Maybe poor adherence has some bearing on the lack of significant toxicity.

    A median of 1.2 years exposure to Truvada can tell us little about cumulative and long term effects. Experience with long term use of Truvada in HIV infected people makes concern about toxicity realistic. Renal toxicity, sometimes severe occurs not uncommonly. It’s mostly but not always reversible on stopping the drug.   Thinning of bones, osteopenia and osteoporosis is also seen. There are additional adverse effects associated with the drugs.

    There were small abnormalities in some paramaters measuring kidney function among those treated with Truvada.  Although these changes were reversible on stopping the drug, the fact that they were seen at all is a reason for great concern about the effects of longer term treatment.

    With the experience we have gained from longer term treatment with Truvada, it is disingenuous to stress its overall safety from just 1.2 years of very inconsistent use.

    It’s important to point out that for HIV infected individuals, the benefits of treatment with Truvada far outweigh the risks.  For uninfected individuals, an entirely different risk benefit analysis must be made.

    Despite the disappointing results of iPrEx, PrEP is important.

    Why is PrEP important?

    There are at least two important reasons.
    1:

    PrEP could protect receptive partners in sexual intercourse, both men and women, who are unable to ensure that a condom is used by their partner and for a variety of reasons are unable to refuse sex .   The best and most respectful way of addressing this would be to find ways to empower these individuals; in some way providing them with the means to protect themselves could be seen to also have the effect of perpetuating their subjugation and abuse.

    But there are women and men who need protection now and providing them with a means to prevent infection that they can control is vital.  This can go hand in hand with working to empower them and helping them to try to ameliorate or leave abusive relationships.

    2:

    Sex is one of life’s joys.  It is vitally important to the human experience.

    Condoms can be a barrier to intimacy which for many is the most essential aspect of sexual intercourse, for both receptive and insertive partners.  So recommending the use of condoms without acknowledging the significant obstacle they may present to a fulfilling sexual experience is a real problem.   Pleasure is part of that fulfilment and for some insertive partners condoms are a significant impediment to experiencing it.

    A fully effective  and safe means of pre-exposure prophylaxis may also allow the removal of a barrier to conception.

    But people are different; for example some individuals have found that condoms can increase intimacy in the reassurance they provide concerning their and their partners safety.

    We should never minimize or trivialize the difficulties condoms can present.  We should also keep in mind that their use is the most effective means of preventing sexual transmission of HIV.

    Their use will remain necessary in order to remain uninfected until we are free from HIV or a safe an effective PrEP method can be found.

    These  considerations, a prevention method that the receptive partner can control,allow conception  and  remove an impediment to full sexual expression are reasons to work towards finding a safe and effective form of PrEP.   If this can be achieved safely and affordably it could even help to bring the epidemic to an end.

    Truvada unfortunately has not proved to be sufficiently effective or safe to be of utility as a general recommendation.  The use of condoms still  remains the most efficient way to prevent the sexual transmission of HIV.

    .

    A few words about prevention education and condoms:

    The  consistent use of condoms is the most effective means to  prevent sexual transmission of HIV.

    PrEP proponents agree but many go on to say that people just don’t use condoms consistently.  This is an attitude that has apparently concluded that prevention education does not and  cannot work.

    But how can one conclude that it does not work when there has been so little of it?   This has some analogy with the claims made for the efficacy of Truvada.   It works, if you take the pills

    .

    If prevention education has been a failure, it’s not because it doesn’t work, but because we have not provided it well enough.  There has been too little and most has not been properly targeted.

    Proper targeting to those most at risk is critical. I have written about this.  We need more and better prevention education.

    The CDC now tells us that the group at greatest risk by far in the US is men who have sex with men.  Nothing has changed except the ethnic distribution, so why are they only telling this to us now?     For over twenty years we were told that AIDS was an equal opportunity infection making prevention education targeted to those at greatest risk even more difficult.

    It’s only now, 25 years too late, that the CDC appears to recognize the urgency of providing prevention education to gay men.

    Neglect of properly targeted prevention education, with encouragement for condom use and continuing support to sustain their use helped to allow the spread of HIV into African American communities in plain view while millions were spent on “America Responds to AIDS” a vacuous prevention message.

    Similarly we have known for years that in the US younger men who have sex with men are at particular risk.  We know where to target prevention messages, but we don’t do it well enough.

    We know that highly targeted prevention education, when crafted by the communities at greatest risk can work.  This was demonstrated in the earliest years of the epidemic in San Francisco and New York City.

    In  1982 when Michael Callen, Richard Berkowitz and I first recommended condom use to gay men in New York City, we stressed that in doing so it was important to celebrate sex, recognizing that  for some individuals condom use, or perhaps more precisely, HIV,  could present a barrier to its full expression.      We have come far in freeing ourselves from long standing societal constraints that for too many have stood in the way of a fulfilling sexual experience burdening it instead with guilt.   It’s important to take care in providing continuing support for condom use and recognize that for many they do get in the way. But it’s really HIV that’s getting in the way, and consistent condom use can help to bring it to an end.

    Finding conditions where sex without condoms is safe is important.   On the showing of iPrEx – despite its ecstatic reception, PrEP unfortunately is not yet ready.

    At the moment consistent condom use is the best protection there is.

    The often uncritical response to iPrEx should not persuade anyone that Truvada  is a safe and effective alternative.

    iPrEx is a large and complicated study.  The investigators deserve the highest praise for completing this difficult phase and for havine provided a result.  It may not be the result that many had hoped for.  But providing clear information is a great achievement and a major advance . iPrEx results clearly show that continued condom use is still necessary to prevent the sexual transmission of HIV.

  • HIV Treatment as Prevention. March 2010

    Posted on March 4th, 2010 admin No comments

    “Treatment as prevention” is in the news again as part of the media coverage of two conferences in California this month where claims were again made that treatment of virtually all HIV infected individuals could bring an end to the AIDS epidemic.

    “Research shows that treatment could end the epidemic in thirty years” is typical of the headlines that enthusiastically announced this proposal to test and treat everybody found to be infected. Sadly, most of the reports I saw failed to comment on the huge practical difficulties that will need to be overcome to make such a project feasible. All ignored a probably insuperable ethical obstacle that will have to be confronted, which may well make the project completely unworkable. Added to these difficulties is the lack of agreement on the soundness of the mathematical model on which the proposal is based.

    This initiative is also described as “treatment as prevention” although I also saw the term “seek, test and treat” used.

    The prevention in “treatment as prevention” results from the reduced ability to transmit HIV that results from treatment with antiviral drugs.

    It’s important to note that “treatment as prevention” can refer to two very different situations where infectivity is reduced by treatment. It describes the mathematical model, noted above that was published about a year ago in the Lancet, an influential weekly medical journal, which claims that the AIDS epidemic could be eliminated with regular tests for HIV and the immediate commencement of antiviral treatment of all who are infected. This is the title of the article: “Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model “ (Reuben Granich and colleagues. Lancet 2009 373: 7).

    Antiviral therapy according to this model would be given to all infected individuals whether or not the individual needs treatment. It would include lifelong treatment of healthier HIV infected people who have not been shown to benefit from it, such as those with more intact immune systems as well as those fortunate individuals whose disease does not progress. This is the root of the ethical problem; people who themselves are not known to benefit from treatment will be asked to receive it for a societal benefit. The benefits of treatment to such individuals are conjectural but as the drugs are not free from adverse effects, the risks are real. Unlike individuals with more advanced disease where the benefits of treatment vastly outweigh the risks, this cannot be known in the case of healthier HIV infected individuals.

    This is very different to the analysis of the reduction in transmission of HIV that results from treating only those HIV infected individuals known to benefit from antiviral drugs. This is also referred to as “treatment as prevention” but unfortunately in none of the reports I saw was the distinction made between treatment only of those who benefit from it and treatment of all infected individuals. These two very different meanings of “treatment as prevention” were almost always conflated by commentators which could quite easily convey a mistaken impression that all HIV infected individuals are known to benefit from treatment.

    Treatment must always be voluntary. But a voluntary decision to receive treatment does not mean a great deal if it is uninformed. The decision can most certainly seen to be coerced if misinformation is supplied. HIV infected individuals must be clearly informed about the risks and benefits of the intervention. As already noted, for individuals with more advanced disease, treatment without question provides a net benefit, but this is not known to be the case for HIV infected individuals with more intact immune systems.   There are suggestions that HIV infection may be associated with morbidity resulting from inflammatory reactions.   It is far from firmly established  if this is indeed the case and if it is, whether  it is an inevitable or even common  consequence of HIV infection, or if it can be prevented or treated with antiviral drugs.   It may also prove to be true that, as claimed by some investigators,  the newer antiviral drugs are less toxic than the older ones.  But the full range of their effects, particularly their longer term effects cannot be yet known. HIV disease can manifest in so many different ways that sorting out what is a drug effect from what is an effect of the infection itself may take a long time.

    For healthier HIV infected individuals, the benefits of treatment remain conjectural as long as clinical trials have not been completed that are designed to provide a reliable answer to the question of when in the course of HIV disease it is best to start treatment. Quite remarkably, about fifteen years after potent antiviral drugs became available no such trial has been completed.

    If a decision about whether or not to receive treatment is fully informed, healthier HIV infected individuals faced with an intervention that is accompanied with very real risks but only conjectural benefits may well choose to remain untreated, at least at that particular time in the course of their disease. The purpose of treatment is to reduce infectivity to others, but many might feel that this can be achieved with greater safety, and even possibly with greater reliability, by the use of condoms.  It should be said though that those researchers who point out the prevention benefits of treatment do not suggest that treatment is an alternative to condoms. On the contrary they recommend that treated individuals continue to use condoms.

    Since the objective of treating all infected people is to end the epidemic, this can only be achieved if a large percentage of infected people receive treatment. But faced with a consent form clearly stating what is known about risks and benefits, it is most unlikely that enough healthier HIV infected people will agree to receive treatment. This is but one reason that if a decision to start treatment is properly informed the project is unlikely to enrol enough individuals to achieve its objective. A danger is that treatment of healthier HIV infected people may be claimed to have a net benefit with greater confidence than is warranted with information we presently have.   To succeed, the project also requires a lifetime of adherence to the treatment regimen.  When drugs are taken without confidence that they are of personal benefit, we cannot know how adherence to the regimen will play out.   Failures in this respect will not only diminish the chances that the project will succeed,  they can also result in the emergence of drug resistant strains of HIV which then could limit treatment options when treatment is needed.

    There evidently is a belief that all HIV infected individuals, no matter the stage of disease will benefit from treatment. But this remains just that, a belief, as long as there is no firm evidence to support it. The evidence there is that healthier HIV infected individuals would receive a net benefit from treatment is of inferior quality, and therefore remains insecure. It comes from some retrospective observational studies. In such studies medical records are analyzed to compare outcomes in individuals who started treatment earlier with those who started later. Such studies however are beset with interpretative difficulties. Because individuals were not randomly assigned to start treatment early or later, a particular outcome, say improved survival of those starting treatment early, may result from whatever the reasons were that treatment was started at a particular time.

    The great benefit of randomly assigning individuals to receive one treatment or another when two are compared is the elimination of interpretative  problems that arise when one or the other course of action is chosen.

    The problem of such confounding factors was also discussed in a previous post: http://aidsperspective.net/blog/?p=75

    The retrospective analysis most frequently cited in support of an earlier start to antiviral therapy, the NA-ACCORD study is also discussed in that post.

    HIV infected individuals and those who advise them surely deserve more reliable evidence to support a decision whether to start or defer treatment than that provided by retrospective observational studies or worse, by mere belief.

    Prospective randomized trials remain the best way to achieve this. They minimize bias, and thus misinterpretation, and remain the most reliable way to resolve uncertainty. There is no getting over this. Such trials may be expensive, and last a long time, but in the end, probably more time and money is lost by repeating inconclusive and conflicting retrospective studies. Surely we need to know, and not guess when it is best to start treatment.

    START is a large clinical trial designed to provide an answer to the question of whether it is best to start treatment early or to defer it.     Another casualty of the pursuit of treatment as prevention that aims to treat all infected individuals is enrolment in START which may become more difficult. Those promoting treatment of all infected individuals as prevention must evidently feel that they already know the answer to be that an early start is best. How can this belief be reconciled with a respect for evidence based medicine that many of same experts claim to have?

    We should rather concentrate our efforts on providing treatment to all HIV positive individuals who are at a stage in their disease where treatment is of unquestionable benefit. The fact that treatment reduces their infectivity to others is an added powerful argument to encourage widespread testing. An additional benefit is that people who know their HIV status are more likely to take steps to prevent infection of others.

    The proposal to treat every infected person as a prevention strategy can be criticized on many levels. I have focussed here on the difficulty that arises from including the treatment of individuals not known to benefit from it. This can usefully be linked to support for and encouragement of enrolment in START.

    The lack of concern for the ethical problem that arises from treating people not known to benefit from it is puzzling. A headline on the front page of the UK Independent newspaper reporting on the proposal to treat all infected people states: “AIDS: is the end in sight?”  The report quotes the opinion of one scientist that “the problem is that we are using the drugs to save lives, but we are not using them to stop transmission”   This statement  is quite remarkable.   The real problem arises when we administer drugs that can have adverse effects to people for any reason other than for their benefit.   We can only ask individuals to agree to take risks for a societal benefit if we have good reasons to believe that the endeavour has a good chance of success – in this case the grandiose one of ending the epidemic.  For reasons outlined above we cannot provide any confidence that this will be so.  At any rate many may feel that their societal concerns can be more safely met by using condoms, a proven way to reduce transmission of HIV.

    I also wrote about this issue for the magazine POZ about a month ago. It can be seen by following this link. http://blogs.poz.com/joseph /archives/2010/02/treatment_of_hiv_dis.html

    I also commented on this issue about a year ago. http://aidsperspective.net/blog/?p=152 This post repeats several points that were made then.

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

    Posted on August 30th, 2009 admin No comments

    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.