Infections

My Fellowship, PrEP And Beyond

Dr David Gillespie is Deputy Director of the Infections, Inflammation and Immunity Division in the Centre for Trials Research – and starts a Health and Care Research Wales Funded Post-Doctoral Fellowship this week. He talks about his background, motivation and ambitions for the future – as well as why he is focusing on research for adherence on PrEP.

Did you always want to be researcher?

Early on during my undergraduate degree I had considered working in finance (e.g. becoming an actuary or accountant). However, a few modules in my second year put me off this somewhat!

How did you get into research?

Part of my undergraduate degree involved a 12-month industrial placement, and I spent mine in the South East Wales Trials Unit. From day 1, the placement gave real purpose to the things I had studied at University. Working in a job that involved continually updating your knowledge, solving problems, and carrying out work that could benefit the health and wellbeing of others meant that it was easy for me to get hooked.

I returned to finish my degree driven and motivated by this experience, successfully applied for a Research Assistant post which began three-days following my final exam, and haven’t looked back since.

Why did you decide to apply for the Fellowship?

There are three key reasons:

  1. My PhD thesis, which I submitted at the end of 2016, focussed on the methodological challenges of measuring, modelling, and accounting for medication adherence in clinical research. While it was a struggle completing it on a part-time basis (while also employed as a full-time member of staff), I enjoyed the freedom it allowed to lead my own work and explore areas that might otherwise be difficult to explore while employed on a collaborative grant. I knew that this was something I would like to experience again, but ideally with protected (i.e. funded) time.
  2. I wanted to gain more experience of leading and delivering primary research. As a Statistician, even working on collaborative grants, you are largely removed from the front-line of data collection and engagement with clinic staff, etc. Indeed, my PhD thesis wholly involved the secondary analysis of clinical data. I felt that this was a gap in my skillset that I wanted to plug.
  3. My lead mentor (Kerry Hood) met with two individuals from Public Health Wales (who are now two of my other mentors) regarding their plans to roll out PrEP across Wales, following Cabinet Secretary Vaughan Gething’s announcement. Following this meeting, she shared their plans with me, and it instantly sparked me into action. This was an opportunity to conduct vitally important research, on a topic of international relevance, using skills and knowledge I had gained during my PhD, while showing a clear progression from the work I had already done.

What was the process like?

I started planning and writing the application towards the end of July (for an end of November deadline). Planning involved identifying mentors. As my plans involved a variety of skills, I approached several individuals and built a mentor team that includes Kerry Hood (Centre for Trials Research), Dyfrig Hughes (Bangor University), Marijn de Bruin (Radboud University Medical Center), Fiona Wood (Division of Population Medicine), Richard Ma (Imperial College London), Zoë Couzens, and Adam Jones (both Public Health Wales). My mentors were great at giving feedback as the proposal developed. I also had meetings with individuals experienced in sexual health and HIV advocacy, as well as those who knew about PrEP from a personal perspective. Other elements of the application which were fairly new to me involved speaking to R&D managers and negotiating NHS support costs for identification and recruitment of study participants.

Once the application form was submitted, it took a couple of months to find out whether or not it had progressed beyond the first stage (internal review and prioritisation). The second stage involved the application going out to external reviewers and an invite to a panel interview. I received external reviews (which were mixed and quite demoralising to read!) approximately four weeks before my interview.

The interview involved a five-minute presentation and questions from a panel of experts (both researchers and PPI representatives). Other than the projector stopping working during my presentation (!!) and completely messing up a stats question, I think the interview went well.

I was the notified of the outcome six torturous weeks later (approximately one year after setting off on writing the application).

Why PrEP?

We have reached a point in time that HIV is a chronic condition that can be managed with medication. Advancements with treatment means that people diagnosed with HIV today have comparable life-expectancies as those living without HIV. However, the number of new cases of HIV being diagnosed continues to remain stable – despite the availability of preventative methods such as condoms and risk-counselling.

Pre-exposure prophylaxis, or PrEP, is the use of antiretroviral medication in individuals living without HIV but who are considered to be at risk of acquiring it in the future (primarily men who have sex with men and transgender individuals who repeatedly engage in condomless anal intercourse, though anyone having condomless sexual intercourse with a person living with HIV with unknown viral suppression is also considered to be at an increased risk of acquiring HIV).

Clinical trials demonstrate that PrEP is highly effective at reducing the risk of HIV-acquisition in at-risk individuals. Additional evidence from clinical research also indicates that when PrEP is taken as prescribed, it is virtually 100% effective in preventing HIV.

PrEP differs from other preventative methods in that it is a preventative action that is removed in time from the risk-event itself (e.g. you can take a pill in the morning and be protected from acquiring HIV through condomless sex later on).

It is a highly efficacious HIV prevention method that could make a real impact on the lives of people who are at-risk of acquiring HIV.

Why is PrEP so hotly debated?

Despite the overwhelming evidence available in favour of PrEP as a HIV prevention strategy, there are concerns around that the use of PrEP will lead to an increase in sexually transmitted infections (as PrEP protects against HIV but not STIs), antimicrobial treatment for such infections, and hence an increase in antimicrobial resistance. This is countered by the proposition that increased STI testing and treatment for individuals accessing PrEP, which is part of PrEP provision through sexual health clinics, will reduce overall transmission. Given that the first treatment for PrEP was only granted a license by the FDA in 2012, there is insufficient evidence to either refute or deny these claims.

Other controversies have included the cost of the branded form of PrEP, but with the UK courts ruling the supplementary protection certificate on Truvada as PrEP invalid (https://pharmaphorum.com/news/truvada-ruling-could-allow-cheap-hiv-prevention-in-the-uk/) this is likely to become less of an issue now.

Debate around the use of this treatment has led to different approaches towards implementation across the UK.

  • In England, PrEP is available on the NHS as part of the IMPACT trial only (https://www.prepimpacttrial.org.uk/about-prep), which has a limited number of spaces.
  • In Scotland, it has been rolled out across the NHS.
  • In Wales, it is available through the NHS for a three-year trial period while further data are gathered – a decision about its long-term roll-out will be made following this period.
  • In Northern Ireland, they are rolling PrEP out through the NHS for a two-year pilot period in a similar way to Wales.

What attracted you to do research in this specific area?

The main thing drawing me to this area was the challenge of measuring adherence to PrEP. Through my PhD, I gained an appreciation of the advantages and disadvantages of different ways of measuring adherence to medication (adherence being typically defined as “the extent to which patients take their medication as prescribed”), but with PrEP it is not as “straightforward” (I write this in jest – it is hardly ever straightforward!) as measuring whether a pill was taken on a given day, as it might be when studying medication adherence to the same medication when used to treat HIV. Adherence to PrEP can only be understood and measured when considered alongside potential exposure to HIV through sexual behaviour.

The planned roll-out in Wales, coupled (in my view) with the lack of adequate measures for PrEP use and (non-evidence-based) controversy around its implementation meant that this was a research area where I felt I could make a difference.

What are the challenges with measuring medication adherence?

The key challenge in measuring whether someone has taken medication is that direct measures (e.g. observed ingestion) is often impractical for all but single-dose treatments. Therefore, there is a reliance on indirect measures, such as self-report, pill counts, therapeutic monitoring, or electronic monitoring. For each of these, an assumption is required, and the plausibility of these assumptions will not be universal for all medicines, conditions, individuals, or contexts.

Why is this type of research so essential?

This study will provide a greater insight into PrEP use than currently known in Wales and the rest of the UK. By considering both detailed longitudinal data on PrEP use and sexual behaviour, it will help identify whether there are certain types of individuals, certain elements of PrEP use, certain behavioural elements, or a mixture of more than one of these three things which may benefit from some form of modification or intervention.

How will you begin? What are the initial areas you will look at?

My initial work will involve a cohort study of individuals accessing PrEP through integrated sexual health clinics across Wales. I will provide study participants with an electronic monitor (that will capture their PrEP use) and as part of the study they will be asked to provide weekly sexual behaviour data. They will be in the study for about 7 months, and I will also be collecting face-to-face data from them when they attend their clinic follow-up visits.

Within this cohort study, I will also embed a qualitative study. When participants finish the cohort study (i.e. they either reach the final follow-up point or they stop using PrEP and hence exit the study) they will be invited for an interview to describe their experiences of using PrEP and forms of intervention to improve their use that may be acceptable.

What specific skills does a statistician bring to this?

As a statistician, I have experience with quantitative study design and analysis. Other skills that I bring as a Statistician include methodical thinking, planning, and the interest in solving problems (though I suppose these apply to most researchers!) As a Statistician who works in a clinical trials unit, I also have an appreciation for the stages that an intervention needs to (or should – because they don’t always!) go through prior to wide implementation, and the sources of bias that require consideration along the way.

Tell us about your other roles across the Centre for Trials Research?

My fellowship provides 60% of my salary, so I will typically be spending 3 days per week on this. Within the Centre for Trials Research, I also have the role of Deputy Director of Infection, Inflammation & Immunity Trials (1 day per week), which involves me providing leadership to this division. For my final day, I work as a Research Fellow / Senior Statistician on a variety of funded studies (and applications for funding), primarily in the fields of infections and intellectual disabilities. I also line manage two members of staff, serve on a number of independent steering committees for other trials across the UK, and get involved in teaching and supervision when the time allows.

How do you manage workloads and working across multiple studies?

Good question! I could probably write a blog post on this alone (perhaps for another day…)* Briefly, the things that help me manage my workload and competing demands are (in no particular order):

  1. Working to understand the values/goals/motivations of i.) Myself; ii.) My project(s); iii.) The CTR; iv.) The College; v.) The University. Understanding where they align and conflict helps me prioritise effectively and work efficiently;
  2. Having a “projects” board which shows me what I have on, so I don’t need to remember this and nothing slips completely off my radar;
  3. Having a weekly to-do list. Any longer than weekly becomes overwhelming (for me at least), any shorter becomes time consuming to write;
  4. Occasionally working longer hours than normal. When I choose to do this, it is so I can get both the thinking and doing time I need to do my job effectively;
  5. Coffee;
  6. Last but not least – resting when I need to. I can’t stress enough how important this is!

Going forward with this fellowship, communication will be vital. I have spent time blocking out days for my fellowship in my calendar, and I am re-configuring my e-mail signature to convey my change in roles. I have also notified the various individuals I collaborate with about the change in my circumstances. I think I will need to accept that the change may not be smooth and might bring difficulties at first – for both me and the people I collaborate with (what change doesn’t), but over time as this becomes the norm things will settle.

* After writing this, I found a really interesting article on work-life balance that resonated with me.

What is the most important thing you would like to see as a result of the Fellowship research?

I would like to see the evidence I generate begin to inform PrEP services in Wales (and the rest of the UK). At the end of my fellowship, I plan to have developed a prototype intervention aiming to optimise PrEP use. While this intervention will need piloting and then formal evaluation (for example, in a randomised controlled trial), the evidence I generate about PrEP use in Wales will still be informative for PrEP users, providers, advocacy groups, and policy makers in this area.

What about the future?

Right now, I am focussed on delivering the plans I laid out in my fellowship proposal. For me, the real success isn’t being awarded the fellowship (as much as a cause for celebration being awarded funding is!) it is delivering it through to its conclusion, and I won’t be satisfied until I have achieved this. It will be a challenge, but I am very much looking forward to meeting this challenge, generating and disseminating vital evidence, and acquiring skills in research leadership.