Foundation Trust, Birmingham; Jane Nicholls, Consultant in Sexual Health, ... HIV Research Trials Unit, North Bristol NHS Trust, Southmead Hospital, Bristol.
● HIV prevention
PrEP: pre-exposure prophylaxis for HIV prevention Matthew Page, Specialist Registrar and Clinical Research Fellow in HIV/GU Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham; Jane Nicholls, Consultant in Sexual Health, Cardiff and Vale Health Board and Sub Investigator HIV Research Trials Unit, North Bristol NHS Trust, Southmead Hospital, Bristol HIV pre-exposure prophylaxis (PrEP) is the use of antiretrovirals by HIVnegative individuals to reduce the risk of HIV infection. In this article the authors give an overview of the evidence for PrEP among key populations and practical considerations regarding HIV and PrEP risk assessment, delivery and monitoring.
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here are approximately 100 000 people living with HIV in the UK, with 5164 people newly diagnosed in 2016. Until recently, HIV incidence had remained fairly stable among key populations despite sustained prevention efforts. A recent reduction in incidence, especially among gay, bisexual and other men who have sex with men (MSM) living in London, has been noted as a result of more regular testing, earlier diagnosis and initiation of treatment.1 An additional factor may be the use of HIV PrEP, a biomedical approach to prevention that is increasingly being used among key populations. With growing awareness and use of PrEP it is important for healthcare professionals to be aware of what PrEP is, who it may be appropriate for and potential issues relating to access and monitoring.
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Figure 1. The Prepster website plays an important role in facilitating awareness of and access to PrEP in the UK
How effective is PrEP?
PrEP regimens have been shown to reduce HIV acquisition among a number of at-risk populations, including MSM, transgender women (TGW),2 heterosexual men and women,3,4 and injecting drug users. The most well studied and frequently used oral PrEP contains a combination of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). TDF and FTC prevent HIV from converting ribose nucleic acid into deoxyribose nucleic acid, thus disrupting its replication and making the virus non-viable. Two dosing regimens for PrEP have been investigated in MSM and TGW; daily and event-based dosing (EBD). Daily PrEP involves taking the same dose at the same time each day. EBD involves taking a double dose between two to 24 hours prior
Trends in Urology & Men’s Health ❘ July/August 2018
to condomless anal sex, and then a single dose every 24 hours for the subsequent sex-free 48 hours. The UK-based PROUD study was an open label feasibility randomised clinical trial (RCT).5 HIV-negative MSM and TGW received either immediate daily PrEP or were deferred from starting for 12 months. The trial was stopped early due to an unexpectedly high incidence of HIV among participants in the deferred arm, meaning that efficacy could be shown despite the relatively small sample size (N=544). There was an 86% reduction in HIV incidence among those on PrEP with a corresponding number needed to treat (NNT) of 13 people for one year to prevent one HIV infection. The efficacy of EBD for MSM and TGW was investigated in the
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HIV prevention ●
IPERGAY trial, a double-blind RCT.6 This showed an 86% risk reduction in HIV acquisition in participants taking event-based PrEP. The NNT was 18 for one year to prevent one HIV infection. Based on this trial evidence, both daily and EBD PrEP have been found to be effective for MSM and TGW practicing condomless anal intercourse. Good adherence is essential, with at least four doses a week required for adequate protection in daily PrEP, and all preand post-doses required for EBD. With good adherence to PrEP, the risk of HIV seroconversion is very low. To date, there are three documented cases of HIV acquisition among individuals who were adherent to PrEP. We acknowledge ongoing trials and emerging evidence with respect to other population groups at risk of HIV acquisition, including heterosexual men and women in sub-Saharan Africa, but these are not covered in this article.
Ongoing HIV prevention trials
There are several ongoing HIV prevention studies investigating other delivery methods and agents for use as PrEP. These include the use of long-acting injectable antivirals such as the integrase inhibitor cabotegravir, infusions with broadly neutralising monoclonal antibodies, and use of intravaginal rings containing the antiviral dapivirine.
PrEP safety and tolerability
The drugs used in PrEP (TDF and FTC) have been used extensively in HIV positive patients. Most PrEP users will not experience any side-effects or issues with toxicities. The most commonly reported side-effects are gastro-intestinal (nausea, diarrhoea) and metabolic (eg low phosphate), and are usually mild and self-limiting. The primary safety concerns with PrEP are renal and bone toxicity. With
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Key points • Tenofovir and emtricitabine is currently the most widely used and efficacious HIV PrEP combination • Men who have sex with men at high risk of HIV and wanting PrEP can either have event-based or daily dosing • Be mindful of renal and bone toxicities as well as drug-drug interactions • Patients taking PrEP should have regular STI screens and be advised on the need for good adherence to reduce the risk of potential HIV infection and resistance • There are new formulations and agents on the horizon
TDF, small changes in serum creatinine and glomerular filtration rate (eGFR) are common and not of concern. However, the drug is not recommended in those with an eGFR of
