Pre-exposure prophylaxis for HIV (PrEP) has been shown to reduce transmission of HIV in a number of trials; however, there is limited evidence regarding the optimal way to deliver PrEP through pre-existing UK services, particularly through fully integrated drop-in sexual health service models. PrEP in the form of Truvada was launched in Wales in July 2017. We set up a PrEP service to be delivered via our drop-in integrated sexual reproductive health service. In the first 5 months of PrEP service provision, we found unforeseen levels of comorbidity, polypharmacy and renal impairment in our cohort of PrEP patients. As a result, we have altered our service model and all patients are now followed up in booked appointment PrEP clinics run by members of the HIV team. Those patients with estimated glomerular filtration rate (eGFR) of 60–70 mL/min or with eGFR of 60–80 mL/min and with comorbidities impacting on renal function are monitored every 4–6 weeks initially, and PrEP has been incorporated into our pre-existing virtual HIV renal clinic for discussion with a renal physician. The PrEP team clinicians report that monitoring and managing the PrEP cohort is now easier in its appointment-only format, although some patients have reported that they would prefer a drop-in system.
- sexual health
- public health
- primary prevention
- pre-exposure prophylaxis
- integrated sexual reproductive health service
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- sexual health
- public health
- primary prevention
- pre-exposure prophylaxis
- integrated sexual reproductive health service
Pre-exposure prophylaxis for HIV (PrEP) has been shown to reduce transmission of HIV in a number of trials1–3; however, there is limited evidence regarding the optimal way to introduce the provision of PrEP into pre-existing UK services, particularly into fully integrated drop-in sexual health service models.
PrEP in the form of Truvada was launched in Wales in July 2017. We set up a PrEP service to be delivered via our level 3 pre-existing fully integrated contraceptive and STI Sexual and Reproductive Health (SRH) open-access drop-in service, which follows a hub and spoke model over a wide geographical area covering urban and rural communities in Aneurin Bevan University Health Board (ABUHB), South East Wales. In this article, we highlight the findings and issues encountered during the first 5 months of PrEP service provision in this setting and discuss the service model we have adapted as a result.
Developing a PrEP service
We set up the PrEP service in line with Welsh operational guidance in conjunction with Public Health Wales (PHW).4–8 The operational guidance was written by the Welsh PrEP Working Group as part of the Welsh Government PrEP Implementation Plan. A literature review was conducted which included models of service providing PrEP in the UK and other parts of the world. PrEP Working Group meetings were attended by Public Health representatives of other home UK nations, including England and Scotland, to facilitate information sharing and best practice around PrEP delivery.9–16 Initially the PrEP service in ABUHB was implemented as follows: Patients with the inclusion criteria shown in table 1 could self-refer or be referred to the PrEP clinic from open-access SRH clinics, where they would have an initial pre-PrEP work-up including full STI screen and renal function assessment. PrEP was commenced in a booked appointment slot in the PrEP clinic staffed by the HIV team, with follow-up via drop-in open-access SRH clinics at 1 month, then 3-monthly. Prior to the introduction of the PrEP service, an internal departmental PrEP pathway was written and a PrEP proforma was developed for our electronic patient record system. Training was provided for both HIV and SRH staff at a Directorate training event, and copies of the pathway, including the tests needed, were placed in all clinic rooms. Clinic times and the service were publicly advertised in conjunction with PHW.4–8
Patients attending also have their blood pressure monitored. The SRH staff seeing follow-up PrEP patients in the drop-in setting were asked to inform the PrEP/HIV team members of their attendance to allow close monitoring of blood results and of any concerns, for example, comorbidity.
Over the first 5 months of PrEP delivery, 96 patients attended for pre-PrEP work-up and were given PrEP clinic appointments for initiation. All were men who have sex with men, with one-third living outside our Health Board area. The mean age was 35.5 years, with an age range of 15–76 years. Of those given appointments, 74 commenced PrEP (taken daily), 2 were diagnosed with HIV on pre-PrEP work-up, 6 declined PrEP, and the remainder did not attend their appointment, including the 2 patients aged under 18. Of the 96 patients, 51 (53%) were known to have been diagnosed with a bacterial STI in the preceding year, with 28 (29%) having syphilis, gonorrhoea, chlamydia or HIV diagnosed on pre-PrEP work-up in our service.
As the service became established over the first 5 months, staff reported concerns that a relatively high number of patients had comorbidities and renal function abnormalities. On review of case notes, 55 (58%) had a pre-existing comorbidity, with 23 (24%) having two or more comorbidities; 51 (54%) were already taking one other medication, with 20 (21%) taking two or more medications. The most common comorbidities and medically relevant issues reported included anxiety and depression (14%), hypertension (9%), chemsex (7%), chronic pain (6%), hypercholesterolaemia (5%), gout (4%), diabetes mellitus (2%), vitamin D deficiency (2%) and deep vein thrombosis (2%). Other reported comorbidities and issues included Crohn’s, psoriasis, epilepsy, alcohol dependence, chronic hepatitis B, undergoing gender transition, recurrent urinary tract infections, prostatism, thalassaemia minor, a genetic chronic immunosuppressive condition requiring long-term antifungal and antibiotic prophylaxis, head injury, hay fever, myocardial infarction, ischaemic heart disease, erectile dysfunction, irritable bowel, reported ‘funny turn’ on Truvada, hiatus hernia, GORD (Gastro- esophogeal reflux disease) , asthma, COPD (Chronic Obstructive Pulmonary Disease) , diverticulitis, pituitary tumour in the past, rheumatic fever, previous anal carcinoma, hypothyroidism, renal calculi and cranial diabetes insipidus.
Of those 18 years and over where estimated glomerular filtration rate (eGFR) had been calculated, 34 (37%) had an eGFR of 60–90 mL/min, of whom 9 (10%) had an eGFR of 60–70 mL/min. One further patient, a 36-year-old with a baseline eGFR of 85 mL/min, developed acute reversible renal impairment (eGFR 25 mL/min at its lowest) after 3 months on PrEP. The higher than expected number of abnormal test results, especially the renal blood tests, and the complex medical histories combined with the complexity of the coding required for surveillance led to several SRH staff reporting loss of confidence in managing PrEP. Several members of the staff raised concerns that PrEP was too complex to be managed via the drop-in SRH clinics, and multiple sample errors, where incorrect tests were done, were recorded. Due to a relatively high number of PrEP patients attending our service initially following the launch of PrEP provision in Wales, the SRH staff experienced difficulty keeping the PrEP/HIV team members informed of PrEP patient attendances across the service, making it more difficult for the PrEP team to monitor patients, thus increasing the likelihood of abnormal blood test results being missed; multiple coding errors were noted to have been submitted to PHW. As a result of these issues, the service was modified to an appointment-only system, as demonstrated in the flow chart in figure 1.
Renal function is now initially assessed at each visit and patients with renal abnormalities and comorbidities are seen at shorter follow-up intervals. At the time of launch, PrEP clinics were set up in an HIV consultant SPA (Supporting Professional Activities) session to meet initial demand. When demand was sustained after the initial launch of PrEP, a pre-existing HIV clinic was changed to a PrEP clinic.
Conclusion and discussion
Overall, we have found unforeseen levels of comorbidity, polypharmacy and renal impairment in our cohort of PrEP patients. Published PrEP studies report lower levels of renal impairment, although it is known that tenofovir can cause renal impairment in patients with HIV.1–3 17–22 Although the PROUD study (Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection)2 demonstrated delivery of PrEP in level 3 sexual health services, there is limited evidence on delivering PrEP in a variety of settings in the UK, although there is some evidence from other countries.23 As a result of the issues we have encountered and in discussion with other services in Wales where PrEP is being offered via an appointment-only system,24 we altered our service model and all patients are now followed up in booked appointment PrEP clinics run by members of the HIV team who are now known as the ‘PrEP team’. This change has resulted in a reduction in the number of coding errors and sample errors. Appointment follow-up with the HIV team members also allows closer monitoring of abnormal blood test results, and patients can have ongoing discussions on the risks and benefits of PrEP with clinicians who have greater experience of using Truvada. Those patients with eGFRs of 60–70 mL/min or with eGFRs of 60–80 mL/min and with comorbidities impacting on renal function (eg, hypertension, diabetes, gout, high cardiovascular risk or who concomitantly take potentially renally toxic medication, eg, non-steroidal anti-inflammatory drugs (NSAIDs), high intake protein supplements) are initially monitored every 4–6 weeks until factors impacting on renal function have been addressed and corrected where possible, and 3-monthly thereafter if their eGFR is stable following the first 6 months of PrEP. PrEP has been incorporated into our pre-existing virtual HIV renal clinic for discussion with a renal physician. All PrEP patients attending have renal bloods and urine dipstick at each follow-up visit during the first 6 months, then 3–6 monthly if their eGFR remains stable over 80 mL/min. Although the positive predictive value of urine dipsticks has been found to be poor in some studies,19 our service has found dipsticks a useful tool, with proteinuria and haematuria on urine dipstick testing predicting the decline in blood renal function on a sample taken on the same day in one patient who demonstrated a decline in eGFR <60 and stopped PrEP.
Patients who have pre-existing medical conditions or who are taking medications that can impact on renal function are encouraged to inform their general practitioner (GP) that they are taking PrEP and allow the PrEP team to write to their GP. Optimisation of care for patients’ medical conditions are discussed at PrEP follow-up appointments; for example, those patients who are found to be hypertensive are strongly advised to attend their GP to discuss this issue further and have their blood pressure monitored. In several cases, this has led to an improvement in patient awareness and management of their hypertension. Those patients taking non-prescribed substances (eg, chems, protein supplements) are advised to stop, with the offer of psychological support to help do so as appropriate. Patients taking medication that may impact on their renal function are encouraged to explore other, less renally toxic, options with their GP and to re-evaluate whether there is an ongoing need for their medication. Of those who have stopped potentially renally toxic substance, for example, NSAIDs, improvements in eGFRs have been observed. However, with all PrEP patients with renal impairment, the multifactorial nature of their histories makes it extremely difficult to determine whether one factor alone is causal in impacting renal function variation.
Clinicians working as part of the PrEP team report that monitoring and managing the PrEP cohort in its revised appointment-only format is easier, although some patients have reported that they would prefer a drop-in system. We have increased the number of PrEP clinics available to patients, including an evening PrEP clinic to facilitate access, with two members of the HIV team changing integrated SRH sessions to PrEP clinic sessions and other members of staff covering the SRH sessions. We are initiating a text reminder service for PrEP patients to improve clinic attendance rates.
Concerns were raised that both patients under the age of 18 who attended for pre-PrEP work-ups failed to attend their PrEP initiation appointment, although one of these patients has re-engaged and is seeing a member of the outreach team for support and assessment. Given the additional complexities of PrEP counselling in those under 18, including safeguarding issues, risk behaviour and the more detailed counselling required regarding bone density issues in this age group,25–28 we developed an additional PrEP pathway for the under 18s, which involves referral to an outreach worker with a special interest in PrEP for 1:1 support, including additional counselling, support to attend appointments, as well as with safeguarding issues, adherence and risk behaviour.
Overall, the PrEP service has been launched successfully and many of the initial issues we encountered have resolved with the change in service delivery model. However, we would welcome further guidance and evidence as to best practice in the long-term management of PrEP patients.
We would like to thank all the staff and colleagues at Directorate SRH Aneurin Bevan UHB, ABUHB Laboratories and PHW for all their support and hard work, in particular Sharon Taylor, Charlotte Cogswell, Clare Lipetz, Alison Sibley and Dr Gareth Roberts, Consultant Nephrologist ABUHB.
Handling editor Sarah K Edwards
Contributors CK, ZC and ATJ sit on the HIV Expert Group and contributed to writing the Welsh Guidance listed for the roll-out of PrEP in Wales. CK set up the PrEP service in our department. CK, IP and HB see and manage the PrEP patients. CK collected the data and wrote the article, and all the authors read it and contributed to changes after the first draft. CK, ZC and ATJ wrote the revision.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement We are very happy to share any further information requested about the PrEP service.
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