Possible drawbacks of PrEP

Despite these advantages, PrEP has a history of being viewed with suspicion as a prevention method and some prevention researchers and advocates still doubt its applicability.

One of the most challenging questions posed is whether it would be simpler and more effective simply to give the ARVs to HIV-positive people. Some advocates are concerned that PrEP could divert resources away from access to ARVs for treatment.

In many situations it would certainly be more logical to give ARVs, for instance, to the HIV-infected partner in a serodiscordant relationship rather than to their HIV-negative partner. However, this is to ignore several reasons people may need or seek out PrEP. They could use it as extra ‘insurance’ in situations where a serodiscordant couple stop using condoms in order to have a child (or simply want to stop using condoms), especially if the HIV-positive partner has an incompletely suppressed viral load. But, more to the point, the primary use of PrEP may be to protect extremely vulnerable people in high-risk populations who are becoming sexually active with multiple partners for the first time, or after a relationship breakup.

There would certainly be a human rights issue if one group was being given ARVs to prevent HIV infection in a country where others were finding it difficult to access them for treatment. It is also an expensive prevention option if it is provided to large populations and taken every day.

This has implications for trial ethics, as well as eventual provision. One of the concerns expressed about PrEP is that it will never be affordable among the populations in which most of the efficacy trials have been, or are being, conducted. At the time the iPrEx trial was being conducted in Peru, for instance, the Truvada (tenofovir/FTC) pills used in the trial were not available for HIV treatment in that country (though the individual drugs were). The Helsinki Declaration¹ says that “medical research is only justified if there is a reasonable likelihood that the population in which the research is carried out stands to benefit from that research.”

There are other reasons why, although PEP and PrEP sound like similar ideas, ‘before’ is a lot more controversial than ‘after’. When we move from PEP to PrEP we are crossing a conceptual gulf. PrEP means giving HIV-negative people expensive and potentially toxic ARVs, not in order to prevent an infection they have already been exposed to, but in order to prevent an infection they might never be exposed to, or which they could avoid by other means.

Everyone can understand why someone might seek help to avoid the consequences of accidental exposure to HIV, but it may be more difficult to explain the need to provide prophylaxis for people who are anticipating taking the risk of HIV infection.

One final area of uncertainty about PrEP is who would get it if it is proven to work, and who makes those decisions and how. PrEP is a highly medicalised intervention that has the potential to create systemic toxicity and HIV-drug resistance and will therefore never (or should never) be sold over the counter; indeed, one of the concerns about PrEP provision in countries without free health care is that it could create a black market in ARVs.

PrEP therefore begs huge questions:

• Who will get it?
• Who will pay for it?
• Would it be more effective to help people use other interventions instead, like condoms?
• Who will decide who gets it?
• How will it be distributed?
• What would be the consequences of a proportion (probably the most high-risk proportion) of the HIV-negative population being on antiretrovirals?
• Which drugs should we use?
• Are we confident that we have any antiretrovirals whose safety is sufficiently well established to allow them to be given to HIV-negative people for a number of years as a preventative measure?
• What is the potential for drug resistance, given that it will be almost impossible to ensure that people who are seroconverting never take PrEP?
• What are the cost implications, not just of the drugs, but of viral load and other tests, which are implied in order to make sure we give PrEP to as few seroconverters as possible?
• The usefulness of a new prevention technology will vanish if people abandon other proven, and possibly safer, measures, such as condoms, in favour of the new idea. If PrEP is not 100% effective, how will that be explained to vulnerable populations?