Just before “Treatment as Prevention” hit the headlines with some controversy, PrEP or Pre Exposure Prophylaxis, was on everybody’s lips.

Whilst some are raving for what they see as the next best thing in HIV prevention, some have expressed reservations about an approach that comes with numerous challenges. Many of those often put forward first are in reality far down the road. Issues of adherence, side effects, potential resistance, cost effectiveness are irrelevant in the short term. Fundamental ethical and rational issues are much more important right from the start.

There is no proof that PrEP works yet, but several clinical trials are ongoing and there are some good reasons to think that PrEP could work, at least within the context of a clinical trial (The closest example we know of PrEP is that of antimalarial PrEP which we know works).

One of the key question about PrEP is who should get it and on what basis?

AVAC which offer a very good range of resources on PrEP remains circumspect on the issue. AVERT on the other hand states that “It has been suggested the PrEP would be an effective way to “protect women (and men) who are victims of sexual violence or coercion, or who are afraid to insist that their partners use condoms”. Worldwide the most common form of HIV transmission is through unprotected vaginal sex with an infected partner. Therefore millions of people could conceivably benefit from taking a pill a day as a way of reducing their risk of contracting HIV.”

PrEP would benefit “millions of people” (emphasis mine). That’s a lot of people, a lot of pills and a lots of days. But that’s not all people; PrEP would only benefit people who are HIV negative.

A necessary prerequisite: getting tested for HIV

PrEP cannot be use by people who are already infected with HIV. Therefore, people who want to access PrEP will need to take an HIV test, not once, but at regular intervals. How often is not known yet, but every 3 or 6 months seems reasonable. Getting people to test once is difficult, getting them to test regularly will be even more difficult but not impossible if testing becomes part of routine healthchecks (an idea facing strong resistance, but this is changing).

Remarkably, regular testing is an issue common to both PrEP and Treatment as Prevention. In each case, testing will lead to the identification of new infections that in turn will require ARV treatment. As PrEP could be rolled out, more people in need of ARV will be identified and there will inevitably be a competition for resources between the sick and the healthy. That we like it or not the problem of access is a reality, and to date despite considerable progresses, less than half of those in need of treatment are receiving it.

It is clear, even for the proponent of PrEP, that it will not be possible to make it accessible to everybody. However, it could be a useful tool in some circumstances for some people, particularly for those most at risk populations (MARPs).

The concept of MARPs is a controversial and contested one. Who is/are the most at risk? Women in Sub-Saharan Africa, Men who have Sex with Men (MSM) and Injecting Drug Users (IDUs) spring to mine. Significantly, they don’t leave in the same place, they don’t contain all those they are describing and they represent very different epidemics.

Still that’s a lot of people. But we could focus to the region the most affected and home to 67% of all people living with HIV: Sub Saharan Africa. This is still a large population that can be sized down if we take into account that in Sub-Saharan African young girls between the age of 19-24 are more at risk. Still that’s the lost of young girls. Which one will be entitled to PrEP? Who will make the decision and on what ground?

The number could be reduced further by focussing on those young girls who are in concurrential relationships (concurrency has been proposed as an important factor in the spread of HIV in Sub-Saharan Africa). But how many are they? This is diffcilut to assess. Fortunately, we know in which part of the population most of new infections are occurring in population where HIV is rife and surprisingly it is low risk heterosexual (figure bellow, see also this article).

“In Lesotho, between 35% and 62% of incident HIV infections in 2008 occurred among people who had a single sexual partner. [...] A similar proportion of new infections (50–65%) was estimated to occur among steady, long-term heterosexual partners in Swaziland (UNAIDS 2009 AIDS epidemic update).”

If PrEP was really to target MARPs, it would have to be offered to a very large number of men and women in steady long-term heterosexual relationship.

That’s PrEP more or less Out of Africa. If we can’t deliver treatment to those who are infected and really need it (See table above), how legitimate is it to suggest delivering ARV to those who could use other means of prevention (existing or in development but not based on ARV).

Next amongst the MARPs are MSM and Sex workers.

MSM are logically expected to benefit from PrEP because they are those most affected by HIV outside Sub-Saharan Africa. In Bangkok a study suggest that 30% of MSM are infected with HIV. The problem is which MSM should be offered PrEP? On what ground will PrEP be provided? Risk behaviour? How will it be assessed and by whom? And how do we reach out those most at risk if we can’t clearly identify them?

Some have suggested that party goers who start partying on Friday night to come back home on Sunday afternoon could benefit most from PrEP. This will require evidences that party goers are having more risky sex than “house keepers”. Should PrEP be offered to those who are not in a relationship and have irregular but numerous sexual partners with whom they don’t use condoms consistently? Maybe, but interestingly, recent research showed that gay men where most often infected by their partner with whom they were in a stable relationship. Should then PrEP be given in priority to gay men who have a main partner rather than those who have casual partners?

Both women in South Africa and MSM clearly illustrate the problem of identifying and quantifying risk, a neccessity if access to PrEP needs to be prioritised.

PrEP for Sex Workers?

Sex workers are also obvious beneficiaries of PrEP but like with microbicides, the introduction of PrEP will compete with a highly effective HIV prevention method (condom). PrEP is also expensive and will not protect against other STIs, does not have contraceptive properties and will put sex workers even more under control of the of customers who will be able to enforce sex without condom.

Pills for life?

A very daunting argument for PrEP is why would we want to put millions of healthy people on treatment when we could much more easily put on treatment the few millions that really needs it ?

Mathematical modeling for PrEP is as unrealistic as that made for Treatment as prevention. A study by John Mellors from the University of Pitsburgh showed and concluded that “the maximum effect of PrEP was observed at the highest level of coverage (75% of susceptible sexually active individuals) with good continuous adherence, such coverage and adherence are not realistic.” Emphasis is mine, but compare level of PrEP coverage with current ARV coverage.

PrEP is not a bad idea on paper. It is even a good idea, on paper, but in the real world it is faced by numerous challenges right from the start from who would really benefit from it to who will ultimately get it.

Disparities in access to treatment are not specific to HIV or to the developing world.  A survey in the UK has uncovered big disparities in the availability of some cancer drugs.  In the case of PrEP add ethical, logistical  and later on adherence, resistance, side effect, effectiveness at population level, cost effectiveness and more, and PrEP comes up as not such a good idea.

It would be dangerous to believe that PrEP would not impact on national health system. Whilst treatment as prevention will contribute to capacity building towards universal access, PrEP will introduce a two tiers/two waiting rooms system.

In the developed world there will be those who can afford PrEP whilst others will still be waiting to receive ARV (many already are). This is particularly relevant in countries where there is a limited public healthcare (See the debate around the Ryan White Care Act). In the developing world, PrEP will divert resources away from immediate needs. I am aware that the same argument was made when ARV roll out was suggested. But there is a huge difference in that provision of ARV for the sick is determined on the basis of a clear measurable factor, the CD4 count. There is not such rational to prioritize PrEP. That’s really the critical point.

Public health is not about withholding or rationing treatment, or about providing it based on the results of a score card. Public health, particularly in limited resources settings is about providing the best options without endangering other’s life. And that’s not PrEP.

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