Increasing demand for PEP in UK, but targets still missed

Surveys from regional hospitals presented to the second BHIVA/BASHH conference in Manchester showed that increasing numbers of patients are seeking post-exposure prophylaxis (PEP) following sexual exposure (PEPSE).

The studies show that there is wide variation in the achievement of some standards, including the variation in the number of patients who are given baseline HIV, STI and hepatitis B tests and the number who attend for follow-up. And although adherence to prescription guidelines is improving, some patients are still being prescribed PEPSE when the likelihood of infection is low.

One study suggested that since the recommended PEP regimen was changed to tenofovir/FTC/boosted lopinavir (Truvada/Kaletra) in 2008, drug side-effects and interactions have been very rare and it might be worth saving costs by not routinely monitoring drug levels and liver and kidney function in patients receiving PEP.

Another study found that the increasing knowledge of PEP has not led to any increase in sexual risk amongst patients prescribed it, at least in the first six months following prescription.

Targets hit

BASHH issued guidelines for the use of PEPSE in 2006 which recommended PEPSE only for unprotected receptive anal intercourse if the partner was of unknown HIV status, or any anal or vaginal intercourse with a known positive partner. Targets suggested by BASHH that trusts should aim for when prescribing PEPSE include:

• 90% of prescriptions are in accordance with the BASHH guidelines.
• 90% of PEP patients take their first dose within 72 hours of exposure.
• 75% of patients complete four weeks’ PEP with minimal missed doses.
• 60% of patients return for an HIV test three months after starting PEP.

Several surveys attested to the increasing awareness and use of PEPSE amongst patients. Surveys from Belfast (McCarty) and from Manchester (Mitchell) found that requests for PEPSE had increased 2.5-fold in 2008/09 compared with previous years, with 8.8 requests per month at Central Manchester Hospital compared with 3.4 per month in 2007/08. The survey from Belfast found that about half of patients coming forward were gay men and this and a survey from Edinburgh (Fernando) reported that about 40% of partners were known to have HIV.

Some centres prescribed PEP in line with BASHH recommendations (99% was achieved in Manchester after standardised forms for assessing PEPSE were introduced), but in others some prescriptions were still inconsistent with guidelines. Nineteen per cent of prescriptions were for non-recommended categories in Edinburgh. Most centres prescribed over 90% of PEP within the 72-hour ‘window period’ but Belfast prescribed 17% of PEP later than this.

Targets missed

A survey of healthcare staff from emergency departments in Southampton and Portsmouth (Rutland) found that only 70% of staff had heard of PEP. Of those who had, 73% were aware it should be prescribed within 72 hours.

While 94% of them would correctly prescribe PEP to partners of known HIV-positive contacts, only 59% would prescribe it to a woman who came in saying she had had anal sex with a man from sub-Saharan Africa – where it is recommended – while 39% would prescribe it to a man or women who had had vaginal intercourse with a partner of unknown status – where it is not.

Completion of PEP and long-term follow-up almost never measured up to the BASHH targets, however. Whether patients completed their four-week course was frequently not documented, but completion rates amongst cases that were documented varied from 55% in Belfast to 32% in Manchester, against a BASHH target level of 75%.

In fact 44% of patients in Manchester turned up for their three-month follow-up appointment and HIV test, so completion rates were probably higher. The BASHH target for three-month follow-up is 60%: three-month attendance figures in Belfast and Edinburgh were 35% and 54% respectively.

Testing people who presented for PEP for existing HIV infection was not universal. In Manchester 76% of patients were baseline-tested, rising to 95% by the end of the study period, but in Edinburgh only 44% were tested. One person tested positive at baseline in Edinburgh, as did one in Manchester, showing that pre-existing infections may be missed, and PEP unnecessarily prescribed, if baseline tests are not done.

Toxicity monitoring may be unnecessary

Monitoring for drug interactions and toxicity has been accepted as necessary for the month people are on PEP. But a study from Brighton of 140 patients on Truvada/Kaletra (Kober) found only one patient, a heavy drinker, whose PEP had to be changed (by stopping his Kaletra in the fourth week) because he had a significant rise in enzymes indicating liver damage. Nine other patients had mild disturbances in liver and kidney function but these resolved themselves. No patient who had abnormal liver or kidney function tests at baseline developed PEP-specific toxicity.

It may therefore be unnecessary to bring in most patients for monitoring during their four weeks on PEP unless they have significantly abnormal baseline tests or the potential for drug interactions.

Risk behaviour decline maintained

Finally, a study from Guy’s and St Thomas’s (GSTT) Hospitals (Loke) looked at behaviour change in 83 gay men given PEPSE. Previous studies have shown that people take fewer sexual risks after having taken PEP, probably because the experience made them re-evaluate their behaviour, but there are fears that if PEP becomes a standard and repeated prevention resource, a subset of high-risk patients may become complacent about risk if repeated PEP is seen as a long-stop solution.

The GSTT study provided no evidence of this. At six months, the proportion of gay men reporting risky sex in the previous three months declined significantly from 51% at baseline to 8.7%, which was itself a further decline from 12% at three months. The proportion reporting new sexually transmitted infections in the previous three months halved, from 16.7% at three months to 8.7% at six months. Twelve-month results are awaited.