More from the latest National HIV Nurses Association study day, held on 6th March. The first part of this blog series can be found here.
PEP and PrEP: the science behind the strategies
Dr Sheena McCormack from the MRC Clinical Trials Unit presented to us on the science behind the PEP (Post Exposure Prophylaxis) and PrEP (Pre-Exposure Prophylaxis) strategies. What stood out for me in this presentation was the fact that the FDA (Food and Drug Administration) approved the use of Truvada for reducing the risk of sexually acquired HIV infection (PrEP), in July 2012, in the US. Although the UK has not yet followed suit, is it only a matter of time before they do? And how feasible will it be to roll it out here? Another thing that stood out for me was learning that HIV is disseminated 5-10 days after transmission yet PEP and PEPSE is given to individuals for up to 28 days after!
Sheena also presented on a number of PrEP studies in the UK including the PROUD pilot study which will look at whether or not a large scale trial of PrEP is feasible, and the level of interest in PrEP in clinic populations. Her concluding thoughts were:
- We cannot ignore what is happening, in particular what the evidence tells us around ‘conversationless sex’ as well as people who engage in condomless sex with multiple partners in-between quarterly HIV tests
- It is common sense to offer treatment to people living with HIV and to offer PrEP to negative individuals; both strategies are strongly supported by the science
- PrEP should facilitate engagement and buy the time required for behaviour change and that more research is needed on PEP.
Further reading on ongoing PrEP trials: http://data.avac.org/OngoingPrEPTrials.aspx
Negotiated safety
Matthew Grundy-Bowers from City University then presented on negotiated safety. Negotiated safety as a prevention strategy is a term that was completely new to me. The term originated from a debate that started in the early 1990s about negotiation in context of HIV risk avoidance amongst gay men. In the 1993 paper Sustaining safer sex: a longitudinal study of a sample of homosexual men, Kippax et al., highlighted that men were more likely to use condoms in sero-concordant relationships. 79% of them had clear agreements about sexual conduct within relationships and 74% had clear agreements about sexual conduct outside relationships. Of these, 39% agreed to no sex outside the relationship; 36% to safe sex both in and outside the relationship; 23% to safe sex with casual partners; and 81% reported never breaking the agreement.
A follow-on paper in 1993 by Erksrand et al., referred to it as ‘negotiated danger’. According to the authors, ‘one of the potential problems of the ‘negotiated safety’ strategy may be that it relies on the ability of sexual partners to reveal their serostatus. There are many factors that may impede such a disclosure, including fear of rejection, embarrassment, and not knowing one’s serostatus. Thus for some at least some of the participants in the Kippax et al cohort, it may be more appropriate to refer to this as ‘negotiated danger’, rather than negotiated safety’.
Kippax et al revisited this in a later paper in 1997 entitled: Sexual negotiation in the AIDS era: negotiated safety revisited. In it they highlighted that; ‘condomless anal sex occurs between two men in a relationship; that sero-concordance is ensured through the testing of both partners, outside of the HIV window period and the bareback sex is negotiated and an agreement is made regarding the sexual conduct outside of the relationship such as monogamy, no anal sex with casual partners or condoms with casual partners, including what to do in the event of a condom break. In addition, some men may include in their agreements strategies for re-testing for HIV and other STIs, especially if they are having sex with casual partners’. This would be quite a comprehensive strategy if adhered to by both partners in the relationship!
However, some challenges exist as regards to this strategy. These include: making assumptions about own or partners HIV status; not testing; not telling the truth about previous risky behaviour; not waiting for the HIV window period and relying on previous HIV tests. For negotiated safety to be effective an agreement must be made about sexual conduct both within and outside of the relationship. Negotiated safety relies on mutual trust between partners.
Matthew concluded that, if executed correctly, Negotiated Safety is an effective HIV prevention strategy. However, if not executed properly it places MSM at significant risk of HIV transmission/acquisition. The nurse’s role is pivotal in providing MSM with the correct information to make an informed choice. And finally, Negotiated Safety should be discussed with all MSM when testing for HIV.
Partner notification in HIV care
Gary Barker from St Helen’s and Knowsley Teaching Hospitals NHS Trust presented on this strategy which would never had crossed my mind had anyone asked me to provide a list of HIV prevention strategies. Gary started off by reminding us that the past few years in HIV prevention have focussed heavily on early testing and treatment as prevention. He posed the question whether partner notification (PN) has been lost amongst all the prevention messages. According to WHO, PN is ‘the process of contacting the sexual partners of an individual with a sexually transmitted infection including HIV, and advising them that they have been exposed to infection’.
The rationale behind PN is to break the chain of transmission; prevent re-infection of the index patient/co-infection; to prevent complications of untreated infection and to fulfill the duty of care. However PN is not a legal requirement.
PN has been an issue in HIV care for a number of reasons including the fact that the point when someone is given a diagnosis isn’t really the most appropriate time to start discussing PN. It is a highly sensitive subject to broach and in order to secure co-operation with PN it is important, amongst other things, to have a non-judgemental approach and to emphasise patient choice/control, to highlight partner at risk of untreated infection and to reassure confidentiality.
He then touched on various methods of PN including identifying partners at risk and novel methods such as using facebook, SMS and internet sites for contact tracing.
Gary then went on to look at proof that PN works. He looked at a study that was conducted with NAT in Sheffield where 135 partners of 74 newly diagnosed patients (62%) were traced. Of those partners traced and tested, 37% were newly diagnosed with HIV. A 2013 joint BASHH/BHIVA PN audit (where 169 HIV services – 13 non GUM, took part), also concluded that PN is an effective strategy for diagnosing HIV.
Gary concluded that PN rates need to be improved. That PN is an effective way of tracing high risk individuals and that services need to move with the times and look at new ways of delivering Partner Notification.
Towards a cure: will it ever be truly achievable
Scott Mullaley from the Imperial College Healthcare NHS Trust rounded up the day by looking at where we are in the search for a cure. He reminded us that ART (Anti Retroviral Therapy) has had the most dramatic change in the survival for people living with HIV. He then went on to look at why ART cannot cure HIV. He explained how HIV incorporates its genetic material into human cell. Once the viral DNA is integrated into the host cell’s DNA, it is present for the life of the cell. That means that some cells have virus that has become part of their genetic material. While that cell is not activated or aka ‘sleeping’, no virus is produced and as such ART cannot do anything and the body’s immune system ignores these cells. These cells are also known as ‘latent cells/infection’. If these cells become activated, the virus will be expressed (woken up). The only way to cure HIV is to eliminate all or nearly all of the latently infected cells.
These latent cells are very rare (about 1 in a million) and can be found in reservoirs (sites) around the body including the brain and the gut.
Strategies for a cure therefore include: eliminating latently infected cells; enhancing HIV specific immunity and making cells resistant to HIV. A cure could take different forms as follows:
- Treating patients in early infection when the reservoir is limited, i.e. functional cure
- Shock and cure – adding in drugs that wake up the immune system to kill these virus expressing cells (sterilising cure)
- Gene therapy – make cells unable to allow HIV to get inside. This is known as CCCR5 deletion gene therapy
- Use vaccination to make the immune system recognise and then remove any latently infected cells
- A whole new range of combination treatments with ART to then lead to, at best remission (control of any tiny amounts of virus)
- Clear all cells that have HIV
As research into a cure progresses, it is important to also look at the social and ethical issues that will inevitably arise. These include the possible mistrust of clinicians and researchers if efforts to find a cure fail; how toxic the drugs will be; what if a cure is only partially effective; or is available to only a subset of people; concerns or issues of beneficience /justice and therapeutic misconception – where participants believe they will be cured.
I personally welcome research into a cure and feel lucky to have witnessed this stage of research in HIV. In the meantime, my view or now is that, we currently already have extremely effective treatment for HIV; treatment that enables people to have a life expectancy almost similar to that of the general population. And in the same vein, treatment that has now been proven to prevent the onward transmission of HIV. That is something to be very thankful for.
