Poorly PrEPPed debate on HIV prevention undermines its management

Health
Wednesday, August 24, 2016
Dr. Jonathan Stanley

 

I have looked into this debate carefully. I have reviewed the evidence of recent trials into HIV prevention through various strategies. I have done this through the lenses of clinical training, experience, and health economics.  I have decided to both rebuff enthymemes against conservatives on HIV prevention and to suggest a strategy that will reduce HIV infection on Pareto principles; that we gain the most benefit from the minimum cost.

Pre-exposure prophylaxis (PrEP) is a gay rights issue simply because it has been made one by gay rights activists.  The truth is that PrEP is by its nature not necessary in the fight against HIV, assuming people indeed wish to fight this infection.

Loading pro-PrEP arguments with enthymemes seeks to deny the public a debate to which conservatives must respond with an overwhelming body of evidence that presents the truth.

HIV transmission in the UK is overwhelmingly caused by unprotected sex.  That lack of protection is, to a great extent, voluntary and may involve irrational delay discounting.  It also involves failure of barrier prevention.  Notwithstanding the major study in San Francisco, STRUT, confirms previous work by IPERGAY and PROUD: condomless anal sex is the reason people seek PrEP in the main. 93% of cases in STRUT and by their recruitment criteria, 100% of cases in the latter.

It is homophobic to construct sexuality as an identity to provide a reputational shield for voluntary, very high-risk transmission through CAS with a high degree of promiscuity in terms of number of partners within a short period.

This description is crucial to understand the drive behind PrEP.  HIV is very highly transmissible during primary HIV infection (PHI), that is, before any symptoms are present or before the infection can be easily identified. This is due to the high titre of virus present during PHI before a significant number of antibodies develop which can be detected by point of care or lab tests. 4th generation tests that include antigen testing can allow diagnosis within 2 weeks of infection.  What is crucial to realise, however, is that if sexual history is not clear there is no one-off test which excludes HIV infection.

This window period is one of the main clinical arguments for prophylaxis in the absence of barrier protection; that even regular testing cannot confirm a partner is not infected if they have been recently exposed to HIV.

CAS is a very risk means of infection. Penetrative sex is a very efficient means of transmission of viral laden fluid to mucosa (internal lining). Men who engage in both activities, described as “versatile”, explain why incidence of HIV remains high in men who have sex with men.

Rectal lining is fragile compared to vaginal lining and is rich in antigen presenting cells (APCs) that direct HIV to their target cells. This richness in APCs is due to the nature of the bowel and its contents; lymphoid tissue is tightly associated with the gut and aeronasal mucosa.  It is important to highlight CAS is no riskier if the recipient is male or female; this increased risk of infection is based on mode and not gender. An exposure through CAS is 20 times more likely to result in infection than unprotected vaginal sex.

It is not homophobic to highlight anonymous CAS as a voluntary and unacceptable high-risk activity that is neither gender nor sexuality specific.

Questions must be asked about how anonymous CAS has become accepted. Drinking and driving are both expressions of freedom and are pleasurable but the campaign against drink driving continues to deliver results by stigmatising the behaviour and this gives confidence to friends to pressure those who are drunk to not drive. This saves many lives and yet the NHS is not lobbied to provide complementary taxis for those who are drunk so they can be driven home; the responsibility rests instead with the individual to make such arrangements.

Stigma can be an effective tool giving crucial approval to men low in confidence to refuse CAS when pressured into it.  Sexuality is not synonymous with sexual confidence and those at risk must be helped to take charge of their sexual health and reject risks proposed to them.

PrEP adherence is crucial to success. HIV infects cells quickly and rapidly acquires resistance, far more so than many other viral infections. This resistance is permanent and so will be passed on to others if acquired. Numerous trials have tested adherence, or compliance, to therapy. It has been seen that compliance varies and is not 100%. HIV has been acquired by men taking PrEP who subsequently have been found not to have had therapeutic levels of drug during exposure. The PROUD study reports bottles of drugs being handed back towards the end of the trial. This assumes no PrEP left the trial by way of gift to other men seeking men (MSM). 

Unmonitored, inconsistent use of PrEP will drive drug resistance higher. PrEP resistant HIV has already been transmitted to MSM who were fully PrEP compliant: this is already not a failsafe prophylaxis. High rates of promiscuity and CAS can rapidly spread Truvada (PrEP) resistant HIV, in patterns seen during the 1980s, where a small number of extremely promiscuous subjects can rapidly spread infection.

MSM are high-risk carriers of HIV but a much larger low risk population exists and that population is everyone else. Anyone can be infected with HIV: about 20% of HIV sufferers are unaware of infection. It is wrong to load a debate on HIV prevention with emotive language on PrEP if such a strategy will only be used for high-risk members of the public unless one explores fully strategies that cover both low and high risk groups together.

That is a universal risk stratified screening of HIV.  This has recently been suggested by the CDC in the United States and there is a chance through the NHS to leapfrog American efforts and have a universal voluntary screening programme following the basis for cervical cancer screening: everyone is at risk even if some are of far higher risk than others.

Universal cervical cancer screening has destigmatised testing for HPV exposure and to an extent desexualised cervical cancer from being the consequence of a sexually transmitted disease. The same universality for HIV testing with Treatment as Prevention (TasP) could reduce to the risk of transmission to everyone and crucially remove any stigma or fear of testing by men who fear being outed as high risk. Instead, the reverse stigma will eventually ensure: there will be no reason for anyone to fear asking someone else’s HIV status before engaging in sexual activity with them.

If PrEP activists truly believe they have a right not to catch HIV then certainly we all have a right to know all reasonable steps have been taken by a potential partner to be tested and treated to prevent HIV transmission.

The bulk of new HIV transmissions come from undiagnosed cases of HIV and this includes primary infection; universal screening will help eliminate established untreated infections as a source of transmission and we can focus on promiscuity during PHI as the main driver for infection that can be tackled with behavioural counselling including condom use (not all types work equally well in MSM) and reasons for CAS.  Gay activists must engage in debate as to the drivers of CAS. This is a lifestyle issue and not imply one of preferring condomless sex.

Studies have shown risky sex, as in any risky activity, to be associated with drug use, heavily use of alcohol, personality issues leading to antisocial behaviour and increasingly use of PrEP.  Drug use in MSM is high and a small group engage in an extremely risky behaviour called chemsex. This is the use of multiple drugs to engage in sex often with multiple partners without protection.

It is advertised frequently on websites used for casual sex including the archetypal site for anonymous sex: Craigslist.  

An advert posted by an “occasionally bearded misanthropic drystone waller from Yorkshire into daily chems (drug use) and clubbing” seeking anonymous sex with “curvy blonde girls but open to a convincing ebony TS (transsexual)” gives first glance impression of how social media can facilitate drug associated risky sex.

 

There is no excuse for websites not to shut down advertisements for high-risk sex where illegal drug use is co-advertised.

Gay rights activists lose credibility in fighting for PrEP when there is not an equally high profile campaign to tackle drug use that drives high risk behaviour nor indeed any consideration for universal voluntary test and treat as a means to drive down transmission through TasP.

Any health economic argument for PrEP is flawed as it refused to consider true value for money for PrEP using ICER or incremental cost effectiveness ratio. That is, the increased benefit and increased cost over best alternative practice. This is barrier protection that alongside TasP has the strongest evidence as published by the British HIV Association.  In fact, given that condoms are both cheaper AND more effective that PrEP as evidenced by analysis of all trials to date, condoms dominate PrEP.

In any other health technology, appraisal dominance precludes the funding of a new intervention. Given no clear reason can be given not to use condoms, PrEP would never be funded if HTA principles were followed as for any other healthcare intervention.

PEP, or post exposure prophylaxis, is provided if a condom breaks. This is not infrequent in clinical practice, though on the whole condoms are evidenced as being every effective and this includes occasional breaks. PrEP does nothing to prevent bacterial STDs like syphilis and gonorrhoea and multidrug resistance to this latter infection is an emerging threat itself. In fact, PrEP has been seen to have caused a boom in bacterial STDs in the United States and this will lead to greater spread of drug-resistant gonorrhoea in the future as condom use falls and episodes of anonymous CAS rise.

Activists for PrEP must explain in advance their plan to control bacterial STDs which are already rising rapidly and will do so even more following PrEP introduction. The uncoupling of HIV from other STDs is politically motivated and has no basis in clinical practice and evidence.  Uncoupling will see multidrug resistant threats to public health emerge for which there has been no consideration paid. The backlash from HIV resistance and STD outbreaks could set social attitudes to MSM back thirty years.

Condoms, PEP and Universal Test + TasP offers a three pronged approach to reducing overall exposure to HIV through a reduction in undiagnosed untreated cases, improvement in health outcomes through early HIV therapy (where Europe lags the US) and a commitment to effective control of all STDs through barrier protection.

We should not take false comfort in social tolerance to high-risk sex on the increasingly unwise assumption its worst consequences can be contained with pills. We are entering a period of relative resistance to medication where sanitation to prevent infection will return as a crucial means of HIV and STD control. Barrier protection for MRSA is now widespread in hospitals where patients are isolated from others and increasingly toxic and expensive antibiotics are now used both to prevent and treat multidrug resistance.

When tackling such infections hospital workers must leave the boards of their hospital wards and approach PrEP activists with the confidence to say “We are working in your future, and it isn’t working.”

Finally and crucially, the PrEP activists must end their prejudice. Using a brute force public relations campaign to push for public funding seeks to prejudge any health economic evaluation as favourable to PrEP or else “divisive”. This undermines social solidarity at the heart of tax funded single payer healthcare: treatment is fully funded and based on need.  To seek another route to a funding decision is to champion two-tier healthcare, with only a silver service for those unable to speak out for themselves.

Health economic evaluation first defines and the problem and identifies all the alternatives. PrEP activists do not do this. They seek to justify their claim that PrEP is worthwhile based on its comparison to placebo. No HEE would take this approach, instead comparing to best available and alternative therapies instead. Given condoms are far cheaper and more effective then PrEP, and prevent other bacterial STDs, condoms dominate a PrEP only strategy. No PrEP strategy covered by randomised control trials considers PrEP superior to condoms nor finds trial subjects unable to tolerate them.

If HEE worked on personal preferences for differing therapies the NHS would rapidly face an unsustainable burden as many advanced small molecule and biological therapies are currently rationed due to cost and that rationing relies on intolerance or failure of alternative therapy. No such scenario has been or could credibly be offered by PrEP activists.

For those who claim PrEP would be used alongside condoms the situation is worse. Even if we ignore data suggesting condom use would fall with PrEP, we are still left with a comparison of condoms vs. condoms with PrEP where condoms are extremely effective alone. This means the additive benefit of PrEP may be less than say 3 or 4%.  There is no serious prospect of funding being provided at £5000 a year in this scenario so while politically more marketable in terms of health economics combination prevention is even less cost effective than CAS with PrEP.

Objective health economic evaluation finds condoms dominate PrEP. Given the costs long term of acquired resistance, a rise in bacterial STDs and reduced use of condoms PrEP may not be cost effective at any price using the purchaser provider perspective NICE uses.

PrEP may have a role through private prescription with appropriate monitoring and it would be preferable to tolerate this as a means of avoiding illicit and unregulated access to PrEP through online purchases that post a serious risk of creating drug resistance. It can be expected that those self-funding are highly motivated to adhere to PrEP remembering all trial participants were by nature highly motivated to adhere. 

In summary, the Bow Group calls for:

  1. Education and awareness of safe condom use, substance counselling and PEPSE, especially for MSM
  2. Universal voluntary testing for HIV, accepting that all sexually active people are at risk

  3. Treatment of HIV infection at the earliest opportunity and, by extension, the promotion of TasP

  4. No funding of PrEP via the NHS but supporting the self-funding of PrEP only with clinical monitoring for resistance and for bacterial STDs. Online purchase of PrEP that does not involve regular monitoring should be banned if professionals consider this a risk to increasing resistance.

  5. Banning anonymous CAS at sex-on-site venues as a condition of licencing, with encouragement of regular HIV screening by patrons. Play safe or not at all.

  6. Crackdown on websites hosting personal adverts facilitating illegal drug use.  Websites are perfectly equipped to filter such adverts.

Dr. Jonathan Stanley is a Junior Doctor, a Fellow of the Royal College of Surgeons, and Health Contributor at the Bow Group