A recent article in the US journal JAIDS, Sugarman & Mayer (S&M), provides a handy outline of the ethical issues around pre-exposure prophylaxis (PrEP) for HIV infection (Sugarman & Mayer). The subject is very topical in the US, now that the Food and Drinks Administration have taken a step ahead of the rest of the world in approving Truvada (tenofovir-emtricitabine) for daily use as PrEP (16/07/12). The real-life impact is as yet unclear (US Truvada roll-out); but the US National Institute of Allergy and Infectious Diseases (NIAID) is currently partnering with local public health departments to set up demonstration projects (US Truvada PrEP demonstration projects). The world will be watching.
One area of issues revolves around “well-being” and has two major aspects. The first concerns the possible development of drug resistance that could compromise future treatment options, in the individual and the wider community, either as a result of erratic adherence (the oral table needs to be taken daily, and is known to have adverse side-effects), or as the result of continued use of the drug after the individual becomes infected with HIV. The second concerns the possibility that PrEP could increase sexual risk behaviours (“risk compensation”) that might overwhelm the capability of PrEP to prevent infection. A second area of concern, that S&M label “justice”, involves the degree of prioritization accorded to PrEP, as against management and prevention through ARV, where resources are scarce. Some have argued that ARV should take priority; others (more counter-intuitively perhaps) have made a case for privileging prevention over treatment. A third and final bundle of issues revolves around the impact of PrEP availability on future trials, both of PrEP itself and other forms of prevention. These relate to the correct “standard of prevention” for study participants, and the inevitable tension, aggravated by the availability of PrEP, between assuring the well-being of participants and answering the research question. S&M cite HVTN 505 as an instance of the need for adaptive trial design. For an excellent chalk-face account of the impact of ethical issues on research gaols (though in relation to preventative ARV, rather than PrEP): see Cohen and Sugarman STI blogs 11/07/12.
Concerns around drug resistance and risk compensation seem not to have been borne out by the US experience to date – though it is early days (US Truvada PrEP demonstration projects). Europe has not yet followed the US example in licensing Truvada for PrEP. Studies indicate the acceptability of PrEP to MSM in London (Aghaizu & Nardone 2013) and Australia (Holt & De Wit 2012). Attempts to model the probable impact of PrEP interventions in a range of settings have reached varied conclusions. Mukandavire and Vickerman (2013), without reference to specific context, conclude that a scale-up of condom use is in most circumstances likely to be more effective than PrEP, but that PrEP could have a specific application in the case of female sex workers; Verguet & Walsh (2012) see a future for PrEP in sub-Saharan countries with high HIV prevalence and without circumcision practice, such as S. Africa; Ying & Barnabas (2013), for the same setting, see targeted PrEP as a cost-effective addition to ARV).