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Clinical update
  1. Lewis Haddow1,
  2. Sophie Herbert2
  1. 1Centre for Sexual Health & HIV Research, Research Department of Infection and Population Health, University College London, London, UK
  2. 2Department of Genitourinary Medicine, Derby Hospitals NHS Foundation Trust, Derby, UK
  1. Correspondence to Dr Lewis Haddow, Research Department of Infection and Population Health, Centre for Sexual Health & HIV Research, University College London, London WC1E 6JB, UK; lewis.haddow{at}ucl.ac.uk

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Since October, clinical research teams around the UK have been busy prescribing Truvada as HIV pre-exposure prophylaxis (PrEP) for participants in the PROUD study who were originally randomised to defer at the time of enrolment. At the time of writing, we have a press release reporting that PrEP is highly protective against HIV: protective enough to amend the protocol and offer PrEP immediately to all participants.1 By the time this round-up is published, it is likely that the interim results will be in the public domain. The trial was originally set up as a pilot with the assumption that the sample size of 545 might be too small to see a difference between arms. That the trial is being amended early means one or both of two things: that the participants were at higher risk of HIV than anticipated and that the group randomised to immediate PrEP were more adherent, perhaps more committed, than participants in previous PrEP trials.

It now seems that the question is not if but when PrEP will reach our formularies. And the uncertainty about how it will be received by the public creates fear. Remember, for example, concerns about sildenafil in the 1990s, how it was going to ruin the National Health Service and lead to ‘sex by postcode’?2 PrEP has been compared with the combined oral contraceptive and emergency contraceptives in separating prevention from the act of sexual intercourse and seems no less likely to attract moral outrage.3 Consider how these moral arguments might play out if the parallels being drawn were with the equally revolutionary innovation of antimicrobial chemotherapy.

Patients’ views on PrEP not straightforward

Against this backdrop, we recommend reading the article by Young, Flowers and McDaid.4 This qualitative study used focus groups and indepth interviews of men who have sex with men (MSM) and African migrants in Scotland to seek views on PrEP and its use. The study participants appeared to demonstrate both confusion and suspicion about PrEP efficacy statistics. Some appeared to be wary of ‘things on the internet’ (even questioning whether the US Food and Drug Administration was a reputable recommendation) and felt put off Truvada by the risk of side effects. Interestingly, many respondents seemed to feel that PrEP was not for them, something to be used by other, more risky individuals. The impressions from reading this paper are that clinicians will face diverse views and levels of knowledge about PrEP, with plenty of opportunity for disconnect between the real and perceived benefits and risks.

PrEP resistance unlikely?

Another PrEP paper with importance for clinicians is a report from the iPrEx study on HIV drug resistance.5 In the active Truvada arm (n=1226) there were 48 infections, of which only eight occurred in the presence of detectable circulating drug levels. Postseroconversion samples from these 48 patients were tested using standard HIV genotype and phenotype assays as well as deep sequencing methods. Only two patients in the active arm showed any drug resistance (the minor lamivudine mutation M184I), and through serial virological and pharmacological assays the authors concluded that drug resistance in seroconverters ‘was limited to those initiating PrEP with unrecognized infection’. Very reassuring, perhaps, but it does not completely close the door on emergent drug-resistant HIV cases, unless users of PrEP abstain from all HIV risk activities during the HIV testing window period and start PrEP immediately after their negative test result.

Gonorrhoea continues to keep us ‘on our toes’

The interim results of PROUD are likely to show high rates of sexually transmitted infections (STIs) among participants. Again, these data are likely to be public by the time of publication. Therefore, clinicians may soon face frequent presentations with STIs in MSM using PrEP, and their sexual partners, and with this will come the inevitable threat of drug resistance. Multidrug-resistant gonorrhoea has recently been reported from Australia.6 The novel A8806 strain was identified in late 2013 in a young European woman known to have travelled to Sydney and central and north-eastern Australia. This strain joins two others reported in the past 5 years: H041, identified in Japan, and F89, reported in MSM in Spain and France. All three were resistant to ceftriaxone, penicillin G and ciprofloxacin, and susceptible to spectinomycin, although the A8806 differed in being susceptible to azithromycin. The travel history of the patient identified in Australia suggests that the geographical origins of A8806 may never be identified, but the same or similar strains of gonorrhoea will almost certainly appear in the UK and elsewhere over the next few years. It is hard to know to what extent the title of a recent review Blomquist et al is alarmist.7 Certainly this makes fascinating and essential reading for those interested in this question who want to prepare for more bad news on bacterial STIs.

Finally, we are presumably not alone in receiving frequent emails soliciting contributions to open access journals of dubious stature. We were amused to read a blog8 describing how a researcher at Federation University Australia's School of Engineering and Information Technology submitted a paper to the International Journal of Advanced Computer Technology containing only the repeated phrase ‘Get me off your ****ing mailing list’. The author was promptly rewarded with a one-word peer review (‘Excellent’) and the opportunity to send a small fee and await publication.

References

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Footnotes

  • Provenance and peer review Commissioned; internally peer reviewed.

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