Wagging Fingers Hasn't Worked; Let's Try Pills

It is very reassuring that a commentator in Kenya has mentioned, albeit briefly, that providing ARVs to HIV negative people will strain resources in a country where it is not even possible to supply all HIV positve people with them.

Many people don't have food, water, cheap drugs for everyday, but deadly, diseases, contraception and family planning, proper education, infrastructure, and a great many other things. Why the obsession with grossly overpriced drugs that will not make any material differenc to most people's health?

But there are some odd remarks in the article. One person mentioned in the article that she had not had sex with her husband for the first three years after finding out that he was HIV positive. Then she started to use condoms.

So far so good. Condoms give a good level of protection if they are used properly and used all the time. There are all sorts of stories about condoms breaking but this should be rare if people really know how to use them properly. And at least condoms are cheap and have other benefits, protecting against sexually transmitted infections and preventing unplanned pregnancies.

But the article is about using drugs to reduce HIV transmission. This would be in the form of pre-exposure prophylaxis (PrEP), where a HIV negative person takes an antiretroviral drug regularly to reduce the probability of being infected, or 'treatment as prevention', where the HIV positive person takes ARVs which reduce the viral load to a level where HIV is a lot less likely to be transmitted.

If condoms are used, is the risk that the HIV negative partner faces going to be reduced further when they also take PrEP? Perhaps so, perhaps a belt and braces policy gives more protection.

But if the HIV positive partner is on ARVs, taking them correctly, responding to them (to the extent that their viral load is low, etc), does the HIV negative partner need to be taking PrEP? Couldn't the HIV negative partner just make sure that condoms are used?

The more important questions are about whether there will be enough money for all HIV positive people to receive the drugs and other care they need, as well as for HIV negative people to receive the most effective prevention assistance available.

Currently, only 20-40% of people in need of ARVs are receiving them. Will the need for PrEP be given priority over the need for ARVs, given that PrEP is for people who are healthy and normal ARV treatment is for people who are sick and will die without the drugs?

But even 'treatment as prevention' is not that straightforward. The majority of people in most African countries do not know their HIV status. Even the majority of HIV positive people do not know their status. How easy will it be to identify all HIV positive people and keep on identifying new infections for as long as they occur.

Apparently Swaziland is going to test its entire population and put everyone found to be HIV positive on ARVs, effectively, 'treatment as prevention' or 'test and treat'. There are only 1.2 million Swazis but an estimated 200,000 of them are HIV positive.

Yet only about 60,000 HIV positive Swazis are on ARVs and the country doesn't even have enough supplies for them. Similar shortages have occurred in other African countries. Health services can barely cope with keeping a fraction of people on treatment, let alone all those who need them.

The Kenyan article continues with the sort of honesty that you wouldn't normally find in an article about HIV: prevention so far has had little impact and the rate of new infections is still very high; sexual behavior change, the main aim of most prevention programs, has not occurred to any great extent.

But UNAIDS and the HIV orthodoxy have, according to the article, been targeting the wrong people all along. They have been talking about reducing numbers of partners, using condoms and even giving up sex altogether. But many new infections occur in mutually monogamous couples, often among people who take precautions and who don't take risks.

The biggest problem with both PrEP and 'treatment as prevention' is that we have been very poor at identifying where new infections are coming from, so we are still, many years and billions of dollars later, in a poor position to know how to traget these expensive interventions, if the money does miraculously appear.

HIV prevention programs are usually targeted at whole populations, many of whom are not at risk. But even those who are not 'at risk' by UNAIDS' criteria become infected with alarming frequency. The plan seems to be to put as many people as possible, HIV positive and HIV negative, on drugs because, rather than despite the fact that, we haven't a clue why most people are infected.

ARVs appear to have an effect, whether used for PrEP or 'treatment as prevention', but we don't really know who to give them to. So we are going to try and give them to as many people as possible, in the hope that it will work, apparently. Is this modern medicine? It's no wonder people are suspicious about 'public health' programs.

ARV Resistance: the Ultimate Pharmaceutical Industry Wet Dream

Few in the pharmaceutical industry wish to discuss the important issue of resistance developing to antiretroviral drugs (ARV). Resistance inevitably develops but the question is, at what rate? In high prevalence countries, which are also resource poor countries, there are very few types of ARV available. So when resistance develops to the common ones, there are few alternatives left and most of them are prohibitively expensive.

Ed Susman discusses resistance, which seems to develop rapidly in the US. The US has one of the highest average spends on healthcare in the world. People on ARVs there are monitored carefully and their regime is changed relatively quickly when the patient is not responding for any reason. This is unlikely to happen in developing countries, where most detailed monitoring is beyond their reach, for a variety of reasons.

Another thing Susman discusses is transmitted resistance, which means that a person with a resistant strain of HIV can transmit their resistance, along with the virus. Therefore the current rate of resistance could rise sharply, especially where HIV transmission rates are high.

This might be an acute problem in countries where there is talk of rolling out PrEP on a large scale or using HIV treatment as a means of preventing HIV transmission. Huge numbers of people will be on ARVs with very little monitoring and probably fairly lax adherence. Given that it takes many months to discover non-response to drugs and provide a change of regime in some rich countries, this problem is going to be a lot more challenging in poor countries.

Susman does not discuss resistance in a context where some, perhaps a lot, of HIV is transmitted non-sexually. If large numbers of people are being treated in unsterile conditions and HIV happens to be transmitted nosocomially, the rate of resistance to common drugs, usually the only affordable ones, could increase and leave many patients beyond help.

As one of Susman's informants says "individuals infected with HIV who respond to antiretroviral regimens can anticipate a life expectancy that is similar to uninfected people, because of the number of treatment options currently available. However, in these young people who already have lost one or two or more classes of drugs, [there will be] limited options for therapy". The options will be a lot more limited in African countries, if there are any options.

Pharmaceutical Industry Front Group Blows its Own Trumpet

Pharmaceutical industry front group AVAC is blowing the usual trumpet for PrEP because some recent trial results have been encouraging. They said predictably little about results which were not so encouraging.

The problem with PrEP still remains: no high prevalence country has managed to put all HIV positive people on antiretrovirals, not even all those who are at the stage of disease progression where it is a serious threat to their health. Why does anyone think they can roll out a drug for people who are not infected with HIV on the grounds that it might give them 'up to' 73% protection?

If 20% of sexually active people are infected with HIV and most of the other 80% are considered to be at risk of infection, will they all be given PrEP? Think of the cost, the logistics, the high levels of resistance, the side effects, things instititutions like AVAC and UNAIDS don't seem to be willing to discuss sensibly.

It also seems like a humiliating climbdown for UNAIDS and all the others who maintained that HIV is almost always spread through unsafe heterosexual sex in African countries (though hardly ever in non-African countries, however unintuitive that may sound). Are all 'risk reduction' strategies now to cease?

Will we instead just give out drugs and ignore the things we appeared to deplore for the last thirty years, promiscuous men, survival sex, commercial sex work, exploitation, early and unplanned pregnancies, early marriage, concurrent relationships, large numbers of partners, low use of condoms, lack of family planning and whatever other issues we have spent so long bemoaning?

Warren Mitchell from AVAC remembered to thank the trial volunteers, presumably mostly guinea pigs who, if they are African, will never be able to afford the drugs and for whom the money to pay for them may never be raised. I don't suppose he was being ironic, either.

Another move which looks suspiciously like a way to vastly increase the volume of ARV drug sales, and thereby increase dependency on drugs and funding, is a strategy called test and treat (or various other names). This involves testing the whole population of a country regularly, perhaps every year, and putting everyone found positive on treatment.

Testing even a reasonable percentage of people in a population once has remained elusive, let alone the whole population or the whole population every year. But even testing once a year is not thought to be enough, so test and treat is still just a theory. And it is well known that early treatment carries a lot of risks that have not yet been adequately explored.

It is to be wondered if people will be obliged to take the drugs by law or if they will face stigma if they refuse. UNAIDS has many years of experience in the use of stigma as a weapon with which to threaten people and punish them for being African so perhaps they have some plans in this area. No disease has ever been beaten by drugs alone so it seems hard to believe that HIV will be the first. But it is great news for the pharmaceutical industry.

[For more about PrEP and HIV issues in Africa, see my other blog, HIV in Kenya.]

Is the Big Pharma Tail Wagging the Dr Dog?

In addition to the good work that the Aids Healthcare Foundation is doing to question the 'fast-tracking' of the use of Truvada as PrEP when it has so far shown such poor efficacy, a group of 55 US physicians have signed a letter, also urging the US Food and Drug Administration (FDA) to delay approval until further tests, which may take years, have been carried out.

PrEP may be a great theory and Truvada may be a great drug. But there is little to get excited about yet. If effectiveness in the real world (as opposed to efficacy in carefully controlled trial contexts) can reach a reasonable level, which would be a lot higher than the unimpressive 44% found in the iPrEX study, then it will be time to consider the use of Truvada as PrEP.

It's good to hear that some doctors are standing up for their patients. Others appear to be in the thrall, or in the pocket, of Big Pharma. Many AIDS and human rights activists seem to have got the wrong end of the stick on this one: people have a right to safe healthcare, not to be used as free lab-rat material.

Interest in PrEP Wanes with Accurate Information about Effectiveness

The Aids Healthcare Foundation is one of the few very influential institutions questioning the wisdom of rushing into widespread use of PrEP before we really know how well it will work, what challenges it may present and whether it is the best option for some, or even any, risk group.

Their survey is worth a look but a couple of the findings in particular caught my eye. Aside from the fact that most people think they are not at risk, even thought they are sexually active and engaging in anal sex, only 42% say they always use condoms. Saying they 'sometimes' (34%) use condoms is rather vague and may not differ from those who 'rarely' (9%) use them. And 15% say they never use them.

These figures for condom use contrast strongly with answers to the question about using condoms if taking PrEP as well. 83% say they would continue to use condoms if they knew that PrEP was only 90% effective. And only 63% said they would be 'very likely' to remember to take PrEP every day.

The need for regular health visits and other measures only reduce the percentage willing to take PrEP a bit but sharing costs puts a lot of people off. $720 a year results in 59% of people saying they wouldn't choose PrEP. The result is not much different when the cost sharing goes down to $400 per year.

But resistance and side effects are taken very seriously by these health conscious people, many of whom only sometimes use condoms when engaging in anal sex. A small risk of kidney damage or bone loss over a long period of time taking the drugs results in 66% saying they would not take it.

And for the possibility of resistance to certain antiretroviral drugs if the user becomes infected with HIV, which may be far more likely than the side effects mentioned, a whopping 71% say they would not take PrEP. Perhaps they are aware of the implications of resistance, one of which is that the cost of their treatment will rocket.

It's good that the Aids Healthcare Foundation are interested in probing the issue of PrEP, rather than joining in the wholly unwarranted jubilation. Perhaps HIV drug users and potential users are aware that resistance, which is so incredibly valuable to the drug industry, is a potential disaster for them.

Can PrEP Be Used As and When People Need it or Must it Be Taken Daily?

So far, PrEP has only been approved for daily use, not for intermittent use. Intermittent use, if it works well, could be a lot cheaper than daily use. It could also be a lot easier to adhere to that way. The side effects of taking strong medication might be reduced. And perhaps resistance would develop more slowly with intermittent use. Who knows?

These aspects of intermittent use will be examined in the HPTN 067 ADAPT study (Alternate Dosing to Augment PrEP Tablet-taking). Of course, the retail price of PrEP will be higher if those eventually using it are only taking the drug when they need it, but individuals should need fewer doses. And the hope is that it will work out cheaper for them. The effect of the availability of PrEP will also be assessed for its effect on sexual risk taking.

Would People Take PrEP Every Day? How Much Would they Pay?

An article by Enrique Rivero discusses the reactions of some people to the concept of pre-exposure prophylaxis (PrEP), the use of HIV antiretroviral medication by HIV negative people to reduce the probability of becoming infected. So far, there has been little written about PrEP that is not industry driven hype.

A study carried out in Peru used consumer marketing techniques to gauge the attitudes of some members of 'high risk' groups there. Apparently cost was a lot more important to them than effectiveness. The amount they would be willing to pay would not be considered much in the minds of the pharmaceutical industry, whose greed is boundless.

But there's also a problem with expectations because people expected PrEP to be 100% effective. In trial conditions, PrEP was only found to be 44% effective, which doesn't bode well for its use outside of trial conditions. People also expressed a preference to use the pill intermittently, a use that has not yet been demonstrated. In the much hyped trial with the 44% effetiveness, participants were supposed to take it every day.

I'm not a big fan of such techniques but they do suggest that the issue of PrEP would be better dealt with through sober research and honest reporting than the infantile hype that we have seen so far.

Also, the lowest cost, which participants preferred, would still be far too high for most Africans in high HIV prevalence countries to afford. PrEP never looked like something intended for people in high prevalence countries but I guess those trying to hawk PrEP still hope that bucket loads of aid money will be spent on it. So they don't want to pitch a competitive price if there is no real need to compete.

The study doesn't show much that couldn't have been worked out beforehand and the methodology will probably cut little ice in the scientific community. Which is a pity, because they seem more interested in marketing PrEP than in genuinely assessing its potential to reduce HIV transmission.

The industry clout behind PrEP seems much too strong to let a few problems like those alluded to in this marketing study have any influence on the process of foisting it on an unsuspecting public. If the study posed any threat at all, it seems unlikely it would have seen the light of day. Or perhaps I'm just too cynical, altogether.