CROI: Study reveals widespread misunderstandings about post-exposure prophylaxis among US doctors

The majority of calls to a helpline set up to advise doctors about non-occupational post-exposure prophylaxis (PEP)against HIV were made too late to offer much or any benefit to the person exposed, a study from united States reveals.

Amy Kindrick of the National HIV/AIDS Clinicians’ Consultation Centre reviewed all calls regarding sexual exposures made to the National Clinicians’ PEP Hotline between January 2004 and September 2005.

She told the Thirteenth Conference on Retroviruses and Opportunistic Infections that 55% of calls were made more than 24 hours after the patient’s exposure to HIV and that 28% of them were made more than 72 hours after exposure. Only 32% were definitely made within 24 hours of the exposure. (In animal studies (Tsai) PEP was 100% effective if administered promptly, but only 50% effective if administered more than 24 hours after exposure.)

Altogether 918 calls concerning specific sexual exposures, excluding follow-up calls, were made to the helpline during the study period. Although the majority (58%) were made by doctors, these physicians were in the main not experienced in giving PEP: only 12% had ever managed more than ten cases. Nearly a third of calls were made from A&E departments.

Clinicians did appear to assess exposure risk reasonably accurately. 54.6% of calls were made about exposures deemed by the investigators to be ‘high risk’ and only 4.8% were low risk. In 30.4% of cases the source partner was known to have HIV.

The main types of sexual risk were receptive vaginal intercourse (38.7%) and receptive anal intercourse by a man (21.3%). However calls concerning oral sex (9.6%) were more common than ones concerning insertive anal intercourse (5.1%) even though this is probably more risky, and nearly as common as all calls concerning insertive sex (9.8%).

However it was the fact that only a third of calls were made within time to start PEP optimally that mainly concerned the investigators.

In a poster discussion on several studies concerning PEP and exposure counselling, chair Michelle Roland of UCSF commented: “People still get the wrong message, which is: ‘You have 72 hours to start PEP’. The message should be: ‘You should start PEP as soon as possible’. You can always stop taking PEP if the risk is re-assessed; you can’t ‘have started’ it.”

She commented that in San Francisco the experience that requests for PEP so often resulted in ‘panic’ by inexperienced physicians meant that all referrals were now made to a single emergency clinic.

Kindrick’s paper was just one of five discussed in the poster forum. Michelle Roland’s own paper discussed not PEP itself but the sexual risk reduction counselling that accompanied it. Her paper studied outcomes, in terms of reduction in unprotected sex acts twelve months after counselling compared with baseline, in 457 people given PEP in 2001-2002.

Previous practice had been to offer five risk reduction counselling sessions during which clients were asked to discuss circumstances around the exposure, contrast it with times they had felt in control of their sexual safety, and determine what level of risk they were happy with.

Her study found that two sessions of counselling achieved a statistically significant reduction in risk exposures among ‘lower risk’ patients (defined as having had risky sex no more than four times before the request for PEP), but that it took five sessions to achieve a reduction in risk among patients who had had more exposures.

Roland commented that despite very active outreach during the study period to high-risk environments such as sex parties and a documented increase in risky behaviour during that time, there was no increase in requests for or provision of PEP.

She said “I am very supportive of PEP as an emergency provision patients deserve, but I actually think it is of interest to only a few.”

A third poster (Rabaud) discussed the tolerability of PEP regimens given at nine hospitals in France. The regimens compared were AZT/3TC (Combivir) plus nelfinavir (Viracpet); Combivir plus lopinavir/ritonavir (Kaletra); Combivir plus tenofovir (Viread); and tenofovir/3TC plus atazanavir/ritonavir.

The regimen containing nelfinavir was significantly less well tolerated, with 34.5% of patients discontinuing a 28-day course of PEP due to adverse events, compared with an average of 20% with the other regimens.

Commentators at the poster session said that they had found AZT-free regimens were better tolerated; questioned the usefulness of Kaletra due to its poor genital penetration; and aired the ever-controversial topic (in PEP terms) of whether to provide two or three drugs.

This topic also came up in a review (Vitoria) of guidelines for the use of both occupational and non-occupational PEP from 41 countries, conducted by the World Health Organization.

All but one country had developed PEP guidelines, though 28% had only done so for occupational exposure. Forty-three countries had a national register of PEP use.

Sixty per cent of countries recommended dual or triple regimens with only 40% recommending only triple ones.

Fifteen per cent did not specify a four-week course as optimal and 10% did not specify a ‘window’ after exposure in which to prescribe PEP.

Vitoria commented that “We did not ask if countries were actually implementing PEP,” and asked if there were audience members from developing countries who had done so. A physician from a clinic in Cameroon he described as ‘remote and rural’ said that although they were fully aware of PEP and the country had guidelines, in many cases access to antiretrovirals had not been possible within 72 hours in cases of occupational exposure.

The final presentation (Gardner) from the Centers for Disease Control did not address PEP as such but rather the frequency with which doctors discussed HIV transmission risk reduction with their HIV positive patients.

It was found that this topic came a very poor fourth, with 37% of doctors saying they ‘always’ discussed it with patients, compared with adherence (84%), opportunistic infection prophylaxis (65%) and ‘taking medicines’ (55%). However discussing substance use came off even worse, being discussed ‘always’ by only 23% of doctors.

Female doctors were 1.7 times more likely to discuss prevention and interestingly Hispanic or Asian doctors were three times more likely than white doctors to discuss the topic. Older doctors (over 38) were twice as likely to discuss prevention as younger ones.

However the study methodology was criticised as setting a ‘very high bar’ in its implicit expectation that prevention would ‘always’ be discussed.