Pre-Exposure Prophylaxis or PrEP

Pre-exposure prophylaxis (PrEP) involves putting HIV negative people on antiretroviral drugs (ARV) with the aim of protecting them from HIV infection. This blog looks at some of the pros and cons of PrEP.

Sunday, December 12, 2010

Universal Access to Water Before Universal Access to PrEP

With the buzz that tends to be drummed up when a clinical trial is not, at least on the surface, a complete failure, it is easy to forget what things are like in countries with high HIV prevalence. IRIN has an article about health systems in Kenya needing an overhaul and the frequency of drug shortages and stock outs. Uganda, Tanzania and other countries have similar problems.

This is not just about drugs. On my other blog yesterday, I cited a systematic review of healthcare associated infections which noted "inadequate environmental hygienic conditions; poor infrastructure; insufficient equipment; understaffing; overcrowding; paucity of knowledge and application of basic infection-control measures; prolonged and inappropriate use of invasive devices and antibiotics; scarcity of local and national guidelines and policies [and] reuse of scarce resources, such as needles and gloves."

This is not just about HIV, either. People suffer from and die from preventable and curable diseases, conditions that are cheap and easy to prevent and cure. Many of these diseases relate to a complete lack of basic scientific, health and hygiene knowledge. Many relate to lack of basic rights, such as clean water and sanitation and a healthy environment.

Many people in East African countries have little or no access to health facilities and it's difficult to know how to view that problem. Because many are infected with various 'hospital acquired infections' (HAI) in health facilities, such as HIV, hepatitis, bacterial infections, urinary infections and numerous others. In fact, high rates of HIV are often correlated with relatively high access to health facilities. The lowest rates are often in places where people don't have access to health services.

Large scale rollout of antiretroviral drugs (ARV) has had mixed results, with many people continuing to die of preventable and treatable conditions, such as TB. The number of people on ARVs is quite a small proportion of those who need them. And countries with big programs are depending on donor funding, which is not guaranteed to get any higher, and may even drop.

So the questions are: will health systems be improved enough to make a better job of supplying the enormous number of people who would be in need of PrEP than has been done with ARVs? Where will all the money come from and will the problem of ARV rollout be solved at the same time? Will health issues other than HIV receive the attention they deserve or will people with needs that can be resolved cheaply and simply continue to be ignored?

PrEP is just a pill, it is not the means for ensuring that people who need it receive it and take it as prescribed for as long as they need it. That's no different from ARV treatment, either. But with ARVs, we know that a sustained program with a wide enough reach is still pretty elusive.

So why are we talking about PrEP as if it is anything more than a theory? Universal access to clean water and other basic rights should have been provided before ARVs, at least people would have something with which to swallow the pills. Otherwise, we're just tinkering with the problem.


Thursday, December 9, 2010

Experts More Muted About iPrEx Results Than Media

The iPrEx trial tested truvada as an oral pre-exposure prophylaxis for men who have sex with men (MSM). The results were moderate, showing a 44% efficacy. The result would have been far higher had adherence been higher. But if adherence was something that could be assured, high and consistent rates of condom use would make PrEP irrelevant.

From what I can work out also, the study did not test the partners of those who became infected with HIV during the trial. This makes the claim that those taking the drug were protected from sexual transmission, as opposed to some kind of non-sexual transmission, somewhat tenuous. This question is crucial and is still hanging over the equally hyped CAPRISA 004 trial, which tested the use of 1% tenofovir as a vaginal gel.

As a result of very low adherence to the drugs in the iPrEx trial, it is not possible to claim with any confidence that resistance will not develop where those taking the drug become infected with HIV, but where the infection is not detected in time. Most of those who seroconverted were not following adherence advice. HIV strains resistant to truvada were detected in two participants who entered the trial with HIV infection that was not detected until later.

The issue of how early HIV infection is detected in people taking PrEP is very important. How regular would testing need to be for the threat of resistance to be minimized? Most people never get tested. Some test once in their life. Very few test regularly. Would quarterly, or even yearly testing ever be logistically feasible or affordable?

Resistance is not just a danger for the person taking PrEP; resistant strains of HIV can be transmitted, perhaps even to people taking the same PrEP formulation. Worse still, resistant strains could infect large numbers in certain sexual networks, for example, where MSM are targeted as an especially high risk group.

Whatever about the use of this drug in rich countries, the feasibility of using it in developing countries seems pretty low. Levels of side effects were not high, but that's not so comforting given that adherence was so low. The drug itself is very expensive but the cost of regular testing of millions of people, even the very possibility of such an undertaking, makes it a luxury that few could afford. Dropping the price of the drug will not make the cost of large scale rollout of PrEP any more affordable.

Interestingly, it is reported in the appendix that rates of receptive intercourse dropped sharply in the first 12 weeks and stayed at about half what they were at the start. Use of condoms during receptive intercourse increased to a high level, also during the first 12 weeks, and stayed high for the rest of the trial. Similar patterns of protective behavior were noted in the CAPRISA 004 trial.

These findings suggest that even people thought to be at high risk of contracting HIV are amenable to taking precautions. Sadly, rollout of PrEP is not expected to include rollout of similar levels of support and monitoring found in clinical trials. But most sexually active people in some African countries seem to be at high risk of HIV infection and health facilities are unable to contain the endemic chest and diarrheal conditions that kill so many, let alone HIV.

Dr Joseph Sonnabend has a good critique of iPrEx which is worth reading in its entirety. It seems as if those who want to latch on to anything that can be dressed up as good news are being allowed free rein to do so. But those who treat the issue more thoughtfully, and that includes those involved in the trial, don't seem to be shouting from the rooftops.


Monday, December 6, 2010

The Health of the Poor: a Valuable Commodity for Big Pharma

Roger Tatoud wonders out loud about medicalisation of sex in OpenDemocracy but I would be more worried about medicalisation of health. PrEP operates by putting HIV negative people on antiretroviral (ARV) drugs in the hope that this will reduce their susceptibility to the virus. And 'treatment as prevention' advocates claim that putting HIV positive people on ARVs will ensure that they are less likely to transmit the virus to HIV negative people.

Both processes are part of what some claim is a new paradigm. However, treatment is not prevention. It may play a part in prevention programs but it is not thereby a prevention paradigm. And PrEP is of little use without other prevention measures, such as condom use. In fact, condom use on its own is probably just as effective as condom use in conjunction with PrEP.

I've only managed to see the first page of an article by Vinh-Kim Nguyen and others, entitled 'Remedicalising an epidemic: from HIV treatment as prevention to treatment is prevention'. But they seem to be arguing something along similar lines.

Prevention has long been underfunded and transmission rates are not declining in many countries outside of Africa. As for the African countries with declining transmission rates, it is not really clear why they are declining. Declines in incidence started long before most prevention programs came into existence. This was also long before significant rollout of ARVs.

But a few tens of millions of HIV positive people is not a big enough market for the pharmaceutical industry, they have to put tens, or even hundreds, of millions of people on drugs even though they are not sick.


Sunday, December 5, 2010

In the Absence of Promiscuity, PrEP is Useless

An IRIN article ends with a comment from Dr Helen Rees: "I'd ask why we're doing these studies in these countries at all if we're not going to implement any of these interventions,...I find that unethical." What I find unethical is that these interventions all assume that HIV is primarily transmitted sexually, despite evidence to the contrary.

However, these drug trials have shown one very significant thing: most African people don't have sex a great deal. Their sexual behavior is not extraordinary. And Modes of Transmission Surveys for Kenya and Uganda show that it is ordinary people in long term monogamous relationships that contribute the vast majority of HIV infections in those countries. And yet HIV transmission rates are extraordinarily high.

If you had unlimited amounts of money, you could unleash PrEP on whole populations. It would be a stupid and dangerous thing to do, but if you think, as the HIV mainstream do, that most Africans have enormous amounts of high risk sex all the time, you might think it would be worthwhile.

But there isn't even enough money to supply half of the people globally in need of antrietroviral (ARV) drugs with treatment. The majority of people globally have never been tested for HIV. The majority of HIV positive people globally don't know their status. And PrEP would require that everyone, or most people, be tested as much as four times a year.

PrEP advocates need to get things in perspective. We know a lot less about HIV transmission than we should, given the amount of study that has been done over the years. We are not in a position to consider HIV prevention programs that involve vastly higher numbers of people (and finance) than current programs, which are struggling, despite claims to the contrary.

It's a sobering thought that HIV transmission rates are still very high in countries with very large ARV programs. Also, death rates are very high among people on treatment. People are dying, not because they are HIV positive or because they have AIDS, but because they have preventable and treatable conditions that are just not being treated.

Developing countries with high HIV prevalence have low levels of education, health, infrastructure and many other factors that are intimately related to rapid HIV transmission. Churning out drugs in ever increasing quantities is not going to change things much, especially if evidence that HIV is not primarily sexually transmitted continues to be ignored.

What we are ethically obliged to do is to be frank and honest about sexual transmission of HIV: we don't know why transmission rates are hundreds of times higher in some parts of some African countries than they are in most countries, developed and undeveloped. Therefore, we cannot continue to base most prevention programs on the assumption that Africans have superhuman amounts of sex.

PrEP may turn out to have some use but we have, as yet, no idea what that would be.

[For more on the false hypothesis about African promiscuity, see my other blog.]