Australia’s national advisory body on AIDS and hepatitis, ANCAHRD, has issued guidance recommending the use of antiretroviral drugs for post-exposure prophylaxis after non-occupational exposures to HIV. This was the subject of an Australasian Society for HIV Medicine symposium on Friday 6 October in Melbourne.
There is continuing uncertainty over the effectiveness of antiviral treatment in preventing HIV after a high-risk exposure. (See Post-exposure prophylaxis for more details.) Despite this, it has become the standard of care in western hospitals to offer rapid access to antiretrovirals for healthcare workers exposed to HIV, for example, through needlestick injuries. One aim of the new guidelines, developed with active ASHM involvement, is to clarify the responsibilities of healthcare workers in relation to non-occupational exposures that could carry equal or even greater risks compared to occupational ones.
The guidelines say three conditions need to be met before PEP is offered. Firstly, that the exposure carried a real risk of transmission. Secondly, that the “source” person is known to be HIV positive or there is good reason to think this likely. Thirdly, that PEP can be offered within 72 hours of the exposure - although this is not to be interpreted too rigidly, as there may be benefit even later.
The guidelines include a table of risk estimates, based on best guesses of the risk of different kinds of exposure. The guidelines support PEP for unprotected anal sex and high-risk oral sex among gay men, unprotected heterosexual sex where one partner is known to be HIV positive, needle-stick and other more unusual exposures. Factors such as presence of another sexually transmitted disease can further increase the risk of sexual exposure.
If the HIV status of the source is unknown, exposure risks must be adjusted using estimates of the proportion of people in the relevant population who are HIV positive. In Australia, with an epidemic that is highly concentrated among gay men and, to a lesser extent, injecting drug users, this would not support PEP being offered to a woman after unprotected vaginal sex with a man of unknown HIV status unless he also had sex with men or had injected drugs.
Finally, to make the 72 hours target a reality, clinics should arrange to see people seeking PEP promptly, as an emergency. (In practice the average time from exposure to starting treatment has been 22 hours.)
What PEP should be offered
The guidelines recommend four weeks of antiviral treatment in all cases, but relate the level of treatment to the level of transmission risk and the likelihood of exposure to resistant virus. There is little evidence that triple-drug therapy is needed to protect against infection, as opposed to treating infection once it is established.
In most circumstances, treatment with only two drugs is recommended (such as AZT and 3TC, as in Combivir or Duovir). This might apply after unprotected anal sex with a casual partner of unknown HIV status or after an injury from stepping on a discarded hypodermic syringe of unknown origin. Obviously, there is a risk of inadequate treatment leading to drug resistance in someone who is infected with HIV despite PEP. The guidelines say this should be pointed out before treatment is started.
Triple drug combinations are recommended only when there is a high risk exposure and the source is known to have a high viral load (10,000 plus using a branched DNA assay or 20,000 plus using an RT PCR) or “advanced HIV disease” or if a viral resistance test has shown that the source’s virus has mutations giving resistance to drugs “in at least two classes”. When triple therapy is to be used, the guidelines strongly recommend that HIV specialist advice is sought.
There is a strong warning against using nevirapine for PEP, following a case reported in the Lancet, where nevirapine led to liver failure requiring a transplant, in a person treated as post-exposure prophylaxis. (This does not make nevirapine unsafe in shorter courses, as used for mother to child transmission in a number of developing countries; and the balance of risk and benefit is entirely different when drugs are used for treatment).
Interim findings from the study
Since 1998, Australia has offered the same treatment for “non-occupational” exposures too, through an observational study that offers standardised treatment and follow-up. The study began in New South Wales but is now national, though in reality, most provision has been in Sydney and Melbourne. Anyone who may have been exposed to HIV can join the study, whether or not they actually take PEP. There has also been an opportunity for those enrolled to volunteer for interview-based research, to enable their experience to inform the development of future services. A telephone hotline is in operation (currently funded to March 2002), which has been advertised in the gay press, to injecting drug users, and among health care workers, especially general practitioners.
Findings from the main study were presented by Belinda O’Sullivan. In New South Wales, from December 1998 to June 2001, 290 people had received PEP and another 22 had been enrolled for follow-up while deciding not to use PEP. 85 people had volunteered to take part in the interview study, giving more detailed information on their exposure and on their experience during and after receiving PEP, if they did so. Since the study went nationwide, more than 100 additional enrolments have taken place.
So far, none of those who received PEP had become infected with HIV as a result of the exposure that brought them to services, though as in a parallel study in San Francisco, some have later become HIV positive through repeated exposure.
Most enrolled people were in the highest risk categories according to the guidelines. Often, they had been encouraged to attend by the person with HIV to whom they had been exposed, most of whom were on antiretroviral treatment. Viral load of the person with HIV was known in 59 cases and was below detection limits in 46 per cent of these. In practice, most people had received three-drug combinations, mostly in accordance with the guidelines. 40 per cent had received PEP initially from their regular GP, 23 per cent from a hospital Emergency Department.
By no means all of the exposures were sexual. Injuries could happen from medical procedures at home, including Factor VIII injection, CMV treatment, and injections with cytokines.
Hilary Korner presented findings from the interview studies, in which structured interviews were recorded and analysed. Generally people were able to identify the risks reasonably, though sometimes risks were overestimated and were clearly influenced by emotional factors such as guilt about the activity that had led to the exposure.
The decision to seek PEP, even when someone was strongly directed towards it by another person, represented a decision to take control over an incident in a person’s life. “I’ve done what I can” would be a typical comment. This did not prevent many people experiencing extreme emotions, for which a lot of support was needed.
Reactions to being given PEP were overwhelmingly positive, even where side effects were experienced. “I’d rather be sick for four weeks than the rest of my life.” People spoke of it enabling them to cope with their anxiety and get on with their work while awaiting test results. There was no evidence of people looking forwards to their next round of treatment – although a minority in the wider study do need more than one course on different occasions.
A more subtle reaction came about as people found themselves reflecting on what it would be like to be HIV positive and to have to take antiviral drugs long-term. One heterosexual man, injured by a discarded needle, reported that his feelings both about injecting drug users and about gay men affected by the virus had changed, to much greater sympathy.
PEP in the context of exposure that happened in the course of relationships highlighted the limitations of current HIV prevention options. A number of men have “condom related erectile dysfunction” – they can’t keep an erection while wearing a condom. One negative man said that he nonetheless wanted his positive partner to have the experience, at least occasionally, of being “on top” for anal sex. This led to risky “safer sex” strategies such as withdrawal before coming, which could easily go wrong. This might be one way in which sildenafil (Viagra) could support safer sex, if it enables some men to wear condoms, who otherwise wouldn’t or couldn’t.
Michael Nelson, of the Albion Street Clinic in Sydney, reported on the New South Wales hotline, “1800 PEP NOW”, a collaborative project among a range of organisations. While many people had enrolled in the PEP study without ringing the hotline, the hotline had taken 399 calls between January and September 2001, and his view was that it served a valuable purpose in enabling people with limited HIV knowledge, including healthcare workers, to access information fast.
Why have guidelines?
The case for guidelines was spelled out by Levinia Crooks, Executive Officer of AHSM, in that when guidelines are absent but PEP is being provided for occupational exposures to medical staff, there will be occasional pressure to provide PEP but no consistent or reasonable response can be expected.
Seroconversions
Dr Nick Medland of the Victorian AIDS Council’s clinic in Melbourne told aidsmap that two gay men out of around 50 treated with PEP there had later seroconverted after further exposure to HIV for which they were not treated. (This is similar to the experience in San Francisco, where a comparable study has been undertaken.) Both men were in long-term relationships with an HIV positive partner, and one of them had experienced severe side effects – nelfinavir-related diarrhoea – with his PEP treatment.
Future developments
It seems that while the direct impact of PEP on the epidemic will always be very limited, its effect on community and healthcare worker attitudes to HIV prevention goes much wider. It can bring people into contact with services, which need to sort out how they respond. There was a consensus that PEP provision should continue to be monitored, with special attention to adverse effects from the drugs. STD screening should be included in the follow-up for sexual exposure, probably a week after the first contact. A national hotline should be maintained and publicised. And the Australian national guidelines should be followed up with state guidelines and model procedures for clinics and general practices to adopt, and clarification of how treatment should be funded.