Is it Safe Yet to Come Out of the Condom?

Dr Joseph Sonnabend has an excellent critique of the iPrEx trial, the use of oral Truvada as pre-exposure prophylaxis (PrEP) against HIV. PrEP is the use of antiretroviral drugs in HIV negative people who are considered to be at high risk of infection. The trial achieved a 44% success rate, which is disappointing, but it's best to read Dr Sonnabend's critique if you're interested in a more balanced account of the trial than you'll find in the mainstream press or in the academic literature.

One of the many interesting points in the article, however, is not about PrEP, it's about HIV prevention interventions that aim to reduce HIV transmission by influencing people's sexual behavior. I have always objected to the view that HIV is almost entirely a result of 'unsafe' sexual behavior in African countries. So this means that I also feel a lot of behavioral interventions are not, despite claims to the contrary, contributing significantly to reductions in HIV transmission.

Dr Sonnabend argues that "If prevention education has been a failure, it’s not because it doesn’t work, but because we have not provided it well enough. There has been too little and most has not been properly targeted."

It's important to note that Dr Sonnabend is not writing about Africa, he is writing about a US, urban context. But what he says about behavioral interventions not being provided well enough is, I think, true of Africa too. And it is only now that PrEP is being bandied about as the solution to the HIV pandemic that others who promoted behavioral interventions in the past are beginning to question their effectiveness.

I am not opposed to behavioral interventions per se, I just haven't heard of any that have been particularly successful in reducing HIV transmission in Africa. But I think exercising some restraint over partner choice, number of partners, unprotected sex, age of sexual debut, unplanned pregnancy and many other things, is important. I also think these measures are important regardless of whether HIV is an issue.

However, in the African context, targeting could refer to two very different issues. The first issue in African countries with high HIV prevalence, I would argue, is not that some people have a lot of 'unsafe' sex but that many people are not being infected sexually. If people being infected sexually can be targeted and can be subjected to appropriate behavioral interventions, that should reduce sexual transmission of HIV.

But as things stand, with the assumption that most HIV is transmitted sexually, there is virtually no targeting. Everyone who has sex is considered to be at risk and anyone who is infected is considered to have engaged in 'unsafe' sex. This is despite plenty of evidence that non-sexual modes of HIV transmission are contributing significantly to African epidemics. Non-sexual modes of transmission need quite different types of intervention.

You might think that those most at risk of  sexually transmitted HIV, such as sex workers and men who have sex with men, would be targeted in African countries because of their levels of sexual exposure. This a second kind of targeting issue, but these groups are almost completely ignored by HIV programming. That's unless you count the self-righteous rhetoric, which needn't cost very much.

Also in relation to behavioral interventions, Dr Sonnabend makes an observation about condoms that is missing from any of the prevention literature I have seen:

"Condoms can be a barrier to intimacy which for many is the most essential aspect of sexual intercourse, for both receptive and insertive partners. So recommending the use of condoms without acknowledging the significant obstacle they may present to a fulfilling sexual experience is a real problem. Pleasure is part of that fulfilment and for some insertive partners condoms are a significant impediment to experiencing it."

Given that condoms are the best behavioral intervention we have got, we need to be realistic about their use, which is often low among those who may be most in need of them. The three hackneyed imperatives, those to abstain, be faithful and use a condom, could all be trumped by one of the most basic and sometimes the most intense of human desires, the desire for sexual intimacy. Perhaps imperatives delivered without any authority whatsoever achieve the opposite to their intended result.

One day, it may be possible to supplement behavioral interventions with PrEP, microbicides and vaccines. But even then, it will be human behavior that determines whether this successfully prevents HIV transmission. As the iPrEx trial has shown, if people don't take the pills, they won't work. Unfortunately, the trial hasn't yet shown that if people do take the pills they do work. There's still a lot to learn about human behavior when it comes to HIV prevention interventions. The question is, will what we learn continue to be ignored?

By the way, it is not safe yet.

Pre-Exposure Prophylaxis, Till Death Do Us Part

Pre-exposure prophylaxis (PrEP) involves putting HIV negative people on antiretroviral drugs (ARV) with the aim of protecting them from HIV infection. So far, such a use of ARV does not give 100% protection. However, like male circumcision and the use of topical microbicides, it could be used along with condoms. Or you could just use condoms.

But the ultimate aim is to develop PrEP that allows people to have safe sex without using condoms (otherwise they will tempt very few). Cynics even suggest that the aim is to allow men who have sex with men (MSM) in rich countries to have unprotected sex, but I don't quite buy that.

The fact that a lot of the clinical trials are taking place in developing countries doesn't mean the people there will eventually benefit from PrEP. But to the pharmaceutical companies that sell ARVs, developing countries represent a huge potential market. That's as long as donors can be persuaded to pay for the drugs. Costs are far beyond what people or governments in developing countries can afford.

There are many questions to be raised about how much the use of PrEP could really help reduce HIV transmission. But my question is about who, exactly, would be the targets of a PrEP program in developing countries, taking Uganda as an example (because I happen to have the Ugandan Modes of Transmission Survey handy).

You might think an obvious target for PrEP would be sex workers. But in the 2009 survey, Ugandan sex workers were estimated to contribute 0.91% of HIV incidence. If you add in their clients and the partners of their clients, that still only comes to an estimated 10.5%. PrEP rollout for these groups, assuming you could actually round them all up, would be very expensive. But it doesn't look like it would have much impact on the overall epidemic.

The largest single group, contributing 43% of total incidence, consists of mutually monogamous couples engaging in heterosexual sex. Bizarre as it may sound, most HIV in Uganda, a virus that is difficult to transmit sexually, is transmitted by very low risk sex.

Those engaging in multiple partnerships, along with their partners, make up 45% of incidence, so perhaps they would be good targets. Again, it would be a mammoth task to round up such a large number of people, let alone distribute drugs to them all and ensure that most of them took the drugs most of the time for as long as they continue to be sexually active.

Think of it this way, Kenya has several hundred thousand HIV positive people on ARVs, that's less than 1% of the population. Around 99% of that money comes from donors. And even that few hundred thousand people is beyond what the countries health services can manage, despite all the donor funding.

The sad truth is that, either you 'target' much of the sexually active population of Uganda, which is not really targeting, more scattergunning, or you will not have any sizable impact on the epidemic. But PrEP is simply not the sort of intervention that you can roll out to a large sector of your population.

An article about the costs involved in rolling out PrEP in Australia cites very high costs just for basic, first line drugs. At up to and beyond 10,000 dollars per person, for the rest of their life, this will not even be discussed in developing countries. And while the drugs will be available at far lower cost in places like Uganda, you are talking about millions of potential recipients. Resistance to first line drugs may only amount to 3 or 4% (if they are lucky) but you can multiply that five or ten times to calculate the addition to costs.

The drugs will be available at far lower prices because drug companies have an uncanny way of knowing just how much they can squeeze out of a 'marketing' situation. Rich countries will pay hefty sums for worthless drugs, or drugs worth very little but in huge quantities. Just look at Tamiflu and the stockpiles of it. They will pay less to purchase drugs for developing countries, but the quantities will be mind boggling and Western run institutions will agree to any price once it's in the hundreds of dollars, apparently.

Talking of Tamiflu, one of the main proposed PrEP drugs is Tenofovir, discussed in glowing terms and voluminous quantities during the Vienna Aids Conference. Another is called Truvada, a combination drug. Gilead is involved in all three.

Another name that crops up is Bill Gates and his Foundation, who are never far away if there is money to be made out of intellectual property. But what will the benefits of PrEP be? If Modes of Transmission Surveys like the one for Uganda are correct, almost everyone that has sex in high and medium HIV prevalence countries is at risk. They can't all be put on preventive drugs, even if it were possible to afford such an intervention.

It may sound as if I am claiming that an almost entirely useless HIV prevention strategy is being advocated for by the very pharmaceutical industry that stands to gain billions from it. And that's exactly what I am claiming. Big Pharma expect billions more dollars, on top of the billions they have already received, to flow from persuading donors to pay for up to tens of millions of healthy people to be put on drugs for a large part of their life, with little or no benefit and possibly a lot of damage. In a nutshell: pre-exposure prophylaxis or PrEP. Remember the name.

NB: I have set up a new blog to discuss the subject of pre-exposure prophylaxis or PrEP.

HIV Eradication

HIV eradication means different things to different people. Some have suggested that HIV could be substantially reduced by universal voluntary counselling and testing (VCT) and universal antiretroviral therapy (ART) for those found to be HIV positive. If it were possible to test every sexually active person around once a year in any population in the world, then it may also be possible to put all those found to be positive on ART.

Personally, I think the chances of testing every sexually active person in a country like Kenya, where a sizable proportion of births are not even registered and many people never see a health professional, are slim. Even testing people once has eluded the Kenyan Government's efforts to date and around 80% of people do not know their status.

I have no doubt that, when the people who came up with such a proposal also come up with a plan on how to implement it, the event will be met with the same level of press coverage. But until that time, I'm sure there will be other plans for eradicating HIV. And if you think universal VCT and ART for those found to be HIV positive is crazy, there is a crazier suggestion and it is already being trialled in Kenya.

Many have heard of post-exposure prophylaxis (PEP), something a bit like the morning after pill for HIV. If you think you have been exposed to HIV infection, through sexual assault, needlestick, accidental exposure to infected blood or any other way, you can visit a suitable medical facility and ask for it. That's if you are lucky enough to live in a country with easy access to such facilities, of course. PEP involves a short course of antiretroviral drugs and it can ensure that you do not become infected with HIV.

That's not the crazy suggestion, by the way. The crazy suggestion is called pre-exposure prophylaxis (PrEP). Anyone deemed to be at risk of becoming infected with HIV can be put on antiretrovirals. This should result in them being much less likely to be infected. If they are already HIV positive but don't know their status, PrEP should result in them being less likely to transmit HIV to others.

That's great, but in a generalised epidemic like Kenya's, all sexually active people are at risk of either contracting HIV or transmitting the virus. Of course, commercial sex workers, men who have sex with men and intravenous drug users are much more likely to contract and transmit HIV. These are known as 'vulnerable groups'. But most HIV here is found among the general population. A relatively small percentage of the country's HIV positive people are members of those groups.

For some, the very idea of providing expensive drugs to commercial sex workers instead of providing them with an alternative to sex work could obscene. And there are other, less radical, harm reduction programmes that could be of use to intravenous drug users.

But another group of people who may be offered PrEP if its trials are successful is 'discordant couples'. Only one member of a discordant couple is HIV positive. Often, the HIV negative partner remains HIV negative for many years, even though the couple may have unprotected sex.

HIV is much more likely to be transmitted in the first two or three months after infection and in the last few months or years, after the progression towards AIDS has started. The period in between can be 10 or 11 years and during this time, HIV positive people are less likely to transmit the virus. Of course, this is a long period of time, and HIV positive people may have many sexual experiences. They may also have other sexually transmitted infections, for example, that could make them more likely to transmit HIV.

The potential for PrEP seems obvious, except that we have not always been very good at assessing what the most important factors are in the spread of HIV. Some point the finger at multiple partners, some say poverty is the main problem, genetic differences in Africans or people of African origin have been blamed, tribal practices, commercial sex work and all manner of things have been blamed.

The problem is that all of these could be important factors and all could play a greater or lesser part in different places and at different times. If we are not very clear about exactly how HIV spread in various countries, that is, the history of the virus's spread, we may not be in a position to make predictions about its future.

At present, people are not always good at taking drugs regularly. Sick people, though, are likely to be better at taking drugs than people who are not sick. That's only a guess, but I can see problems with many people remembering or even bothering to take drugs when they are not sick. The drugs may even have side effects or interfere with other drugs they are taking.

Taking drugs for a large part of your life requires certain changes in lifestyle that many may not like to make, if it were even possible for them to make those changes. Drugs can also fail for various reasons. And resistance can develop among people using a drug for a long time, especially if they don't always stick to the recommended regime.

PrEP, if it is ever practicable, will be a very expensive and dangerous shot in the dark if we are not able to predict what the major trends are in each country and, indeed, in each part of each country. But then, some people are unworried by danger when lots of money is involved. Especially if the danger affects other people, far away from home.

And if HIV is eradicated? Well, then we can go on to other transmissible diseases, non transmissible diseases, poverty, malnutrition, food insecurity, fuel insecurity, exploitation, water and sanitation and, well, there are just too many things to list. These, I would suggest, are some of the underlying conditions that allowed HIV to spread in the first place. In Kenya, many of these are getting worse; we are losing sight of them as we allow ourselves to be distracted by grand proposals for the eradication of HIV.

Of course, we could try to deal with some of those other problems first or at the same time as trying to prevent the transmission of HIV. And then, by the time transmission of HIV is reduced as substantially as the mathematical models predict it will be, we may truly have something to celebrate.

(For further discussion of PrEP, see my other blog, pre-exposureprophylaxis.blogspot.com)