HIV Drug Regimes: the Good the Bad and the African

The reactionary (or 'mainstream', if you prefer) view of HIV transmission in African countries is that it is predominantly a result of 'unsafe' sexual behavior. Early interventions to reduce transmission included exhortations to 'abstain' from sex, to be 'faithful to one faithful partner' (or something like that) and to use condoms (an approach that later became known as ABC). Most people didn't know what words like 'abstain' and 'faithful' meant, but they became very good at repeating them until other interventions were dreamed up.

Like 'ABC', more recently touted interventions such as mass male circumcision and pre-exposure prophylaxis (or PrEP; the use of antiretroviral drugs by HIV negative people with the expectation of reducing the risk of infection), also depend on replacing some kind of 'unsafe' behavior with some other kind of behavior, deemed to be safe, or safer, or fervently hoped to be safer. Both circumcision and PrEP require that people also adhere to the strictures of the ABC approach (and if the name sounds paternalistic, that's exactly what it is).

Ever-paternalistic when writing about Africa, the BBC has heard that "some sex workers are having unprotected sex - and taking antiretroviral drugs afterwards to cut the infection risk". This is called post-exposure prophylaxis, or PEP. It has long been available in developed countries to people who are accidentally exposed to HIV, through their occupation, as a result of sexual assault, etc, although it is probably not as widely available in high HIV prevalence countries with inadequate health services, low levels of education and poor drug supply systems.

The BBC article is claiming that sex workers should be using condoms, but sex workers themselves are pointing out that they can make more money if they don't use condoms; clients are often willing to pay more. Most sex workers don't have the massive number of clients that media outlets such as the BBC have reported in the past, so they need to get as much money as they can each time they do get a client. The BBC is also 'concerned' that sex workers are using PEP too often; some say the drugs should only be used a maximum of once a year, otherwise they may cease to be effective.

In contrast, those touting PrEP can't speak highly enough of the use of drugs to reduce the risk of HIV transmission (as a look back through previous posts on this blog will show). Trials of such drugs are promoted in frequent press releases, perhaps in the hope of receiving the customary spontaneous standing ovation that some announcement must receive at every AIDS conference. The media generally picks up the press releases and spreads them far and wide, sometimes embellishing them with an extra layer of gilding.

PrEP and PEP are different. In general, PEP is taken after exposure. PrEP is taken before exposure by a person who faces a high risk of infection, or who is thought to face a high risk (which is just about every sexually active person in high HIV prevalence countries). But there are different versions of PrEP, daily and intermittent. The daily version involves taking the drug every day; but the intermittent version is taken just before sexual intercourse, or even just after.

Both versions require strict adherence to the regime, but it's clearly a lot easier to take a drug just before or just after a specific event than to take a drug every day because you or someone else considers you to face high risks of infection. Intermittent PrEP is still being studied, but the general tone of Big Pharma press releases about PrEP is that it is a great thing, that trials are doing very well, and that if people (and governments) will just pay their exorbitant prices, everything will be great. Strangely, the tone used about PEP is usually far more measured; perhaps PEP is just not lucrative enough as a market?

But the BBC can't resist the temptation to point (or at least wag) their finger. If people in African countries are infected, it's because of their behavior. If interventions don't work it's because of people's behavior. If drugs don't work it's because of lack of adherence. If people don't appear to be following instructions it's because they are failing to 'adhere to the regime'. If people are infected and know it wasn't because of their sexual behavior they are said to be 'under-reporting', or simply lying. Etc.

You get the picture. We are clever and they are not. Some people writing on the subject are even happy to use the word 'stupid', because the 'good AIDS/bad AIDS' dichotomy didn't disappear in the 1980s, as it should have. It lives on in the media, in popular books about AIDS and various other sources. There are also different drug regimes available for the good and the bad, those who were infected 'by accident' and those who are 'reckless'.

Could PrEP be in Competition with Mass Male Circumcision Programs?

After years of trying to create a market for pre-exposure prophylaxis (PrEP) pills, such as Truvada, Big Pharma has turned to their favorite mass marketing ploy: dumping their products in African countries that are starved of health funding. Of course, why wouldn't they dump them in Africa, won't they be paid for with donor funding?

An article in Kenya's The Star entitled "Kenya: 'Wonder Pill' for Risky Sex On the Way" takes the unusual step of raising some difficult questions about PrEP, rather than repeating the Big Pharma press release, despite a shaky introduction. The article continues "Kenyans involved in risky sex behaviours will soon get a 'wonder pill' that can prevent HIV infections. Experts say Truvada, which some call the 'new condom', can reduce chances of catching HIV but there are fears the drug may be misused by the youth".

What, exactly, would constitute misuse of the drug? If it can cut the risk of infection by "up to 75 per cent if one faithfully swallows it daily", what could go wrong? Well, as the article eventually reveals, most people don't swallow drugs daily and most people can not expect 'up to 75%' reduction in risk. That figure is not even from a randomized controlled trial, but from a 'sub-group' study, where the best results are used to exaggerate the level of protection people, in (comparatively) strict trial conditions, may expect. Outside of that sub-group, and outside of drug trial conditions, risk reduction is far lower.

It's odd that such reports talk about studies and proofs for something that they then refer to as a 'wonder pill', a 'new condom' and talk of 'up to 75% protection' (although that's a bit weak compared to the term 'invisible condom' used by those marketing mass male circumcision), and the like. These are PR buzzwords, not scientific findings.

It is said that PrEP programs intend identifying those most at risk of being infected, such as sex workers, intravenous drug users and men who have sex with men. This will be a departure from vilifying these already stigmatized and criminalized groups; it remains to be seen how much donor funding will actually be spent on these groups to provide them with PrEP, given that it has been so difficult in the past to provide them with condoms, injecting equipment and even basic sex and sexuality education.

As the article says, Truvada is expensive, and it has made billions of dollars for Gilead. So it's worth their while pushing as much of the stuff as possible in countries with high HIV prevalence while the patent guarantees that their product will face little competition. By the time the patent expires the likes of Bills Clinton and Gates will surely have set up some program whereby the drugs can continue to be purchased at inflated prices.

The article makes the important point that nearly 1 million HIV positive Kenyans currently need antiroviral drugs just to keep them alive. So why would donors want to provide these same drugs to people who are not yet infected with HIV (aside from an obvious desire to enrich big pharma)?

Oddly enough, a cost effectiveness study makes its estimates using existing levels of male circumcision and antiretroviral therapy. This means that the three multi-billion dollar programs will be in direct competition with each other for funding, and each one will be trying to claim that any drop in HIV incidence is a result of their work. The study also seems to assume far higher levels of success than have been achieved so far. But that's big pharma for you.

While Gilead and other pharmaceuticals can gain a lot from any increase in antiretroviral therapy and PrEP programs, they may not stand to gain from mass male circumcision programs. Their assumption that their PrEP programs will be cost effective only in countries where circumcision levels are low suggests that by the time their product may be approved, the circumcision programs will already need to have failed, some time around 2015.

Worries that people may use PrEP as a kind of recreational drug, so they can dispense with the use of condoms when they are engaging in sex with people who may face a high risk of being HIV positive are not very convincingly addressed; nor are worries that overuse and misuse of antiretrovirals, either for HIV positive people or as PrEP, are brushed aside, with remarks about "government policy" and making the drug available "in form of a package that probably includes HIV testing and other prevention methods".

I seem to remember condoms, circumcision, ABC and various other programs being made available in the form of a package, without that leading to extraordinary results. But it will be interesting to see if PrEP will erode some of the funding currently being made available to, or earmarked for, mass male circumcision programs.

Circumcision programs stand to rake in billions for the big providers, but widespread use of PrEP would be worth far more. It's unlikely that a full scale version of both programs could co-exist; they are not mutually exclusive, but their cost effectiveness is predicated on their being the only or the main program in high HIV prevalence countries.

Whether one program displaces another, or whether they all get funded, the losers will be people in high HIV prevalence African countries, which will continue to suffer from under-funded health and education sectors. They will continue to be a mere 'territory' for sales reps, who will continue to carve things up in ways that should be very familiar to us by now.

Treatment Action Group Raises Concerns About Thai PrEP Trial

The media reacted predictably when it was announced that a pre-exposure prophylaxis trial in Thailand showed some promise in reducing HIV transmission among intravenous drug users (IDU). However, many raised concerns throughout the course of the trial about how it was being conducted. One concern was that clean needles were not provided to trial participants, even though these are known to be the best means of reducing transmission among IDUs. But there were other serious issues that put a question mark over the value of the trial.

Another observation is that "the extent to which tenofovir protected against parenteral versus sexual exposure is unknown". The extent to which sexual versus parenteral exposure may have been involved was never questioned in many other PrEP trials, in mass male circumcision trials and in trials of numerous other HIV prevention interventions. Many HIV related trials fail to account adequately for modes of transmission, assuming that the virus is almost always transmitted sexually, often despite evidence to the contrary.

I'm just curious to know why these concerns have been raised by the Treatment Action Group about this trial in particular, when serious concerns about some other HIV prevention trials don't seem to be heard much, at least, not without attracting accusations of 'denialism' and similar ad hominem responses.

Give ARVs To Those Who Need Them; PrEP Can Wait

It's been a while since I've written anything about PrEP and it's hard to keep up with two blogs. But there have been a few articles on the subject. One, and I've only seen the abstract, finds that PrEP has high acceptability but that adherence and use are more challenging. This may be a reflection of the sheer idiocy of throwing drugs at a disease that is treated in almost complete isolation from all other diseases, from the conditions in which people live, from their overall health status, etc.

Interestingly, people on PrEP ran the risk of being perceived as HIV positive, giving rise to stigma, rumors and relationship difficulties. A paper about lymphatic filariasis reports that people have difficulty understanding why they should take pills for a condition for which they have no symptoms, and also why they should take the same pills for what they see as two different conditions (swollen legs and swollen testicles).

The authors of the PrEP article note that "adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work". The research into giving antiretroviral drugs to HIV negative people took place in Kenya, a country where many HIV positive people with a critical need for the drugs are not receiving them, and where many babies are still being infected by their mothers (or perhaps through some other route that antiretroviral drugs will not be able to address, such as through unsafe healthcare).

A review of a mathematical modelling study of PrEP mentions the ethical problems of rolling out such a program in a country where many HIV positive people are not yet on antiretrovirals. The article finds that the strategy would be cost effective in a middle income country, such as Peru, but only if it was highly targeted. However, this is where PrEP and most other HIV interventions come unstuck in African countries. HIV in high prevalence African countries is characterized by not disproportionately affecting just a few easily identifiable groups. While prevalence is high in certain groups, the largest groups of HIV positive people don't have obvious sexual risks that could easily be targeted. Also, these groups are far too large for any African country to afford.

What I don't really understand about PrEP though, is why it is necessary at all. Proponents of the use of antiretroviral drugs in as many scenarios as possible (early treatment, lifetime treatment for women receiving prevention of mother to child treatment, etc) tell us that someone on ARVs is not very infectious. If PrEP could be targeted at people who are thought to be at risk, targeting those who put them at risk would seem like a much better prospect; that is, targeting people who are already HIV positive. They are a far smaller group, for a start, and this would be a good reason for putting all HIV positive people on ARVs as soon as they have a clear clinical need for them.

PrEP is Win-Win for Big Pharma, Lose-Lose for Ordinary People

When a PrEP trial produces poor results, the reaction is often to point the finger at the patient: they didn't take the drugs regularly, 'adherence' was low, etc. The irony of this is that people thought of as good candidates for PrEP are often those who have not successfully modified their sexual behavior, or have shown themselves unwilling to do so. If they will not or can not modify their sexual behavior, why would they be more willing or able to modify their drug taking behavior?

Some drug trial reports parcel up the high achievers and exclude the low and medium achievers and call it a 'sub-study' or something similar. But the point of a randomized controlled trial is to make it clear what kind of result can be expected of people taking part, not what kind of result can be expected if everyone behaved as drug manufacturers would wish them to. Given that people don't behave in real life as they do during drug trials, the results for strategies such as PrEP so far have been somewhat encouraging, but not good enough to roll out the strategy.

Even with PrEP, people are encouraged to engage in safe sex, to limit their number of partners, to use condoms, etc. If they can't or won't do some or all of those things, PrEP will not be very effective; but it may not have any positive impact at all. Those behind the trials and those producing the drugs are anxious to portray the strategy as tested and proven, but it is most definitely not, not yet anyhow. One of the main exponents of the strategy tries to persuade us that PrEP is the way to go, but some of his readers are clearly not convinced. And the opposing case raises additional concerns about PrEP, referring to the strategy as 'grasping at straws'.

In countries where HIV prevalence is very high and transmission is highest among low (sexual) risk groups, those engaging in heterosexual sex with one HIV negative partner, PrEP is not going to be feasible. Those who face the lowest risk, but are paradoxically the highest risk group in Modes of Transmission Surveys, are unlikely to be targeted by a PrEP campaign.

And given that the majority of HIV positive people in need of treatment are still not receiving it due to cost, infrastructure, political and other reasons, it would be odd to offer the same drugs to people who are still HIV negative. It would seem far better to establish what exactly the risks are and address those risks before throwing yet more drugs at the problem. But PrEP is the way to go if you want to sell lots of drugs to healthy people; if that doesn't work, you'll then have lots of sick people to sell even more drugs to.

Truvada Manufacturer Gilead Stops Funding to Critics

The Aids Healthcare Foundation (AHF) provides healthcare for HIV positive people and advocacy in the broader field of HIV health. In that capacity, the AHF has criticized the pharmaceutical company Gilead Sciences on a number of issues, including drug pricing policies.

But in addition, AHF has questioned the use of Gilead's Truvada as a pre-exposure prophylaxis (PrEP), a pill to be taken by HIV negative people to give them some protection from HIV infection. It could be taken, for example, by someone whose sexual partner is HIV positive. However, PrEP is not as effective as using a condom and it doesn't protect against other sexually transmitted infections.

More importantly, using a drug like Truvada can give rise to the development of drug resistant strains of HIV, especially in users who are unknowingly infected when they start taking the drug or who unknowingly become infected while taking it. AHF have argued that every time someone gets a prescription for Truvada, they should also be able to show that they have been tested for HIV and the result is negative.

Drug manufacturers are not known for their tolerance of public accountability; as a result of AHFs actions, Gilead have stopped their funding to AHF. This is particularly unfortunate right now because approval for Truvada as PrEP, which was expected to be rushed through the usual regulatory procedures, has now been delayed so that the requirement for a negative HIV test be stipulated. But it's likely that Gilead will continue to lobby for the right to aggressively pursue their own ends at the expense of public health.

The increasing dependence on drugs with outrageously high prices is worrying even in a wealthy country like the US. But as the country has the highest HIV prevalence in the Western world, it would be an even bigger threat to the country's public health systems if widespread resistance to Truvada were to develop. As well as resistance developing in an individual taking the drug, resistant strains of HIV can also be transmitted to others.

Also of concern is that, up until now, HIV drugs have been used by HIV positive people. The use of the same drugs by people who are HIV negative should be raising questions in people's minds about how far public health should go with what is effectively medical treatment for perfectly healthy people.

They may even ask how far it is possible for public health to go; the number of healthy people should, hopefully, far outnumber the number of sick people; it's undoubtedly a great market. But some level of drug resistance is inevitable. So are companies like Gilead stealthily creating new markets for even more costly second line drugs by vastly increasing the number of healthy people taking Truvada?

Experts Unambiguously Opposed to Saying the Wrong Thing

Apologies for the lack of posting this year but I have had enough work keeping my other blog going. The subject of PrEP and related issues do also crop up there, though.

Daily use of Truvada has been backed for pre-exposure prophylaxis use by a panel of 'experts', which generally refers to people who are so well paid to say the right thing that no one else will disagree with them. It's likely that this use of the drug will soon be approved by the FDA. I wasn't able to find a register of the 'experts'' interests but I'm sure it would make interesting reading.

If approved, the drug will be prescribed for HIV negative people who are thought to be at high risk of being infected sexually, which generally refers to men who have sex with men in Western countries. The drug is not being considered for use by intravenous drug users. It is also unlikely to be of much value for commercial sex workers in wealthy countries as they are rarely infected unless they are also intravenous drug users or face other serious risks.

This suggests that PrEP is unlikely to be effective in high HIV prevalence developing countries, where high risk groups are not easy to identify. In many African countries, the bulk of infections among adults occur in married people and those in long term relationships, who don't face very high sexual risks. In other words, the drug is of little use as PrEP where it is most needed. But I'm sure that won't stop Big Pharma from lobbying the right people so that the potential tens or hundreds of millions of Africans can be exploited.

The process of palming off useless but extremely expensive drugs with potentially dangerous side-effects on Africans has been eased by years of publicity for the dominant HIV transmission paradigm, which says that almost all HIV in African countries is transmitted through heterosexual behavior. The fact that the paradigm is seriously challenged by empirical data has done little to influence policy, which concentrates on the politician, religious leader and media friendly process of wagging fingers, pointing fingers and poking fingers into the many HIV fuding pies.

Opposition from groups who claim to represent the interests of HIV positive people has almost all been taken care of in the time honored fashion of paying off anyone who speaks out of turn (or rubbishing anyone who won't take payment). A rare voice of dissent comes from the Aids Healthcare Foundation, which has consistently opposed the current trend of rushing into practices which have little empirical backing, but which mysteriously receive full backing from 'experts'.

Pharmaceutical front group Aids Vaccine Advocacy Coalition (AVAC), predictably, blow the trumpet for PrEP; pharmaceutical products ostensibly produced to treat illness would never have become as profitable if they were only used by sick people. But the UK's Nick Partridge puts his finger on the problem, probably inadvertently: "But we need to know if people at highest risk of infection are prepared to take a pill every day and whether there would be an increase in risk-taking behaviour which could outweigh the prevention effectiveness of Truvada."

The truth is, we don't know who is at highest risk in high prevalence countries, we know that most will not take the pill every day and it's very likely there will be an increase in risk-taking behavior, especially where people opt for PrEP because they know (or even think) they are at risk.


[For more about non-sexual HIV transmission and male circumcision, see the Don't Get Stuck With HIV site.]

Tenofovir Products in Search of a Market

A few days ago, an article appeared on AidsMeds.com about the drug Tenofovir being associated with an increased risk of irreversible kidney disease, which does not reverse even when the drug is no longer taken. Tenofovir is one of the main ingredients in a vaginal gel developed to reduce the transmission of HIV, although a recent trial was stopped early because the gel was found to be ineffective. Another trial of Tenofovir taken orally as pre-exposure prophylaxis was also stopped early as it was clear it would not be possible to demonstrate a difference in effect between the drug and a placebo.

Despite these findings, Poz.com reports that the US Food and Drug Administration (FDA) has accepted an application from the makers of Tenofovir, Gilead Sciences, to give a priority review of the use of the drug, in combination with emtricitabine, to be marketed as Truvada. Despite some less favorable findings about Tenofovir, the more favorable findings led to immediate calls for application for use as PrEP to be fast-tracked.

In addition to the above worries about Tenofovir, widespread use of PrEP is also likely to give rise to drops in use of condoms. This possibility is denied vigorously by defenders of PrEP, and some data has been produced to support that defence. But like male circumcision and the hormonal contraceptive Depo Provera, people tend not to think about dual protection against both HIV and unplanned pregnancy.

Interestingly, while injectable versions of Depo Provera and similar methods are said to be 'female controlled' relative to the oral version, this objection doesn't appear to be used or alluded to by proponents of PrEP or vaginal gel.

A paper has been published discussing these diverging trial results and the authors pay particular attention to adherence to the drug regime, which needs to be very high. The authors mention identifying "optimal populations for PrEP"; but they may find that these populations are least likely to need the drug. It's all beginning to sound like a product in search of a market; but where would Big Pharma be if it never took that approach?

Science Awards: Virtuous Circle or Spooky Cabal?

There are few things that make me think 'collusion of interested parties' than prominent awards, with the exception of peer reviewers, who always me think of Freemasons for some reason. For all I know, though, they could all be completely innocent and/or unrelated.

Anyhow, Science Magazine has awarded two of their ten prizes to the highly controversial and unconvincing Tenofovir vaginal gel (the CAPRISA 004 trial) and the almost equally unconvincing pre-exposure prophylaxis drug (the iPrEx trial). There is a lot of USAID and PEPFAR funding behind both of these, so the poor trial results may not matter too much.

The ongoing concentration on capital hungry technologies and technical expertise tends to mask one of the biggest problems that poor countries face: shortage of skilled health personnel. Here in Tanzania there is one doctor for approximately every 50,000 people (compared to about one for every 170 people in Cuba). What are people going to do with all these drugs and other technologies, assuming they can ever afford them?

This problem, like many of the other real problems developing countries face, is ignored by the cabals of industrialists, megaphilanthropists, technologists, politicians, religious fanatics and other jackals of the HIV industry. But it is not going to just go away.

Of course, it's of little interest to the same interested parties, who wish to establish markets, not undercut the very source of their current and future wealth. In addition, HIV related technologies need to be put through rigorous trials in countries with high HIV prevalence to prove their worth. So even if 'aid' money will not be diverted to subsidize these markets, contacts with developing countries need to be maintained. After all, that's what 'aid' is, a tool of foreign policy.

Botswana has announced that it is going to concentrate on prevention, and not before time. The country has one of the worst epidemics in the world. But perhaps now they will reject the self-serving arguments about treatment 'being' prevention and about HIV funding 'strengthening health systems' or about it  not diverting funding from other health issues. If only other high prevalence countries, and even low and medium prevalence countries, would follow suit and stand up to the moneyed interests.

Botswana simply can't afford antiretroviral drugs at current levels of usage, never mind the annual increases in incidence adding to the costs, along with resistance and other factors ensuring that costs will rise exponentially, not linearly, in the future. All high prevalence countries with large numbers of people on antiretroviral drugs are experiencing the same problems as Botswana.

But Botswana also seems to have realized that much of the money spent on behavioral interventions has been wasted. Perhaps they'll take another step and realize that this failure of behavioral interventions may be because HIV transmission is not all about sexual transmission?

Using mere technologies to solve deeply rooted development problems is as likely to work as planting seeds on the moon (in its present state). And if I thought the HIV industry really wanted to solve development problems, health and HIV related problems in particular, I would think they are behaving like fools.

But I don't think anyone seriously believes such naive claptrap. They are business people, involved in protecting their markets and ensuring that they make as much money as possible, regardless of the consequences for people in developing countries.

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.

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.