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?

Apologies for Lack of Posting

It's been some time since I have been able to write a post for this blog but I will get back to it as soon as possible. I also write about the lunacy of prohibitively expensive and purely technical approaches to what are public health and development issues on my HIV in Kenya blog and also on the Don't Get Stuck With HIV blog and website.

Treatment As Prevention: Dream or Nightmare?

In the light of current enthusiasm for 'treatment as prevention (or 'is' prevention or some other permutation)', it's sobering to read an article from the US entitled 'Only 28% of HIV patients have condition under control'. The idea of treatment as prevention, sometimes referred to as 'test and treat', is that it will be feasible to test about 80% of an entire population, not just once in a while, but regularly, perhaps once a year or more. Upon being found HIV positive people will receive immediate treatment, regardless of clinical stage.

The US spends over $7,000 per capita according to WHO estimates for 2009; that's over 15% of GDP. Tanzania, in contrast, spends $57 per capita, 4.5% of GDP. So if only 28% of HIV positive people in the US are rendered unlikely to transmit the virus to others through having a low viral load, at least through (safe heterosexual) sex, and about 20% of those infected don't even know they are positive, where does this leave countries like Tanzania?

Figures for how many Tanzanians are on antiretrovirals vary a lot and are vague; they don't make it clear what percentage on treatment have the virus under control. Quite a lot of people said to be on treatment are lost to follow-up every year. Many die or move to another area, but this also suggests that numbers on treatment are overestimated as some are registered in more than one place. The majority of HIV positive people in Tanzania are not on treatment and a majority of the population have never been tested for HIV. A large number of people who have never been tested are estimated to be HIV positive.

I just don't feel convinced that the money is going to be stumped up to test tens of millions, perhaps hundreds of millions of people every year for the foreseeable and to treat tens of millions for several decades to come. But perhaps I'm just a sceptic (or 'skeptic' if you're in the US).

Tenofovir Vaginal Gel Trial Stopped Because It's Ineffective

The Microbicide Trials Network (MTN) have announced that Tenofovir gel will no longer be used in the current VOICE trial (Vaginal and Oral Interventions to Control the Epidemic) shortly after the same decision was made about the oral version. Both arms of the trial have been stopped for the same reason; neither are any more effective than a placebo. Trials of Truvada, a combination of tenofovir and emtricitabine, will continue for the moment.

Incidence, the rate of new infections, was extremely high, at 6%. I wonder if the trial has got any closer to figuring out just why HIV transmission is so high among study participants? For instance, were sexual partners tested and were their HIV types matched? Were possible non-sexual HIV exposures investigated, for example, through unsafe healthcare, traditional healthcare, cosmetic practices, or any others?

All the talk about 'fast-tracking' approval of tenofovir by the US Food and Drugs Advisory for possible production by 2014 that we heard so much of just a year ago has been replaced by the kind of silence we've come to expect from results that can't even be dressed up to look a little bit positive. With viable gels and PrEP pills so far in the future, it might be a good idea to put into effect some low technology (though far less lucrative) HIV prevention programs.

The full results of VOICE are unlikely to be available for some time, perhaps another year or two. But if good data is collected on non-sexual transmission, the thousands of participants will not have wasted their time completely. It won't be much consolation for the hundreds of people whose infections were not prevented, nor the hundreds of thousands of new infections that will occur elsewhere in the meantime, but everyone will benefit if a little less attention is paid to their sex lives, which may not be as relevant as orthodox HIV theory suggests.

Mitchell Warren, the Executive Director of the AIDS Vaccine Advocacy Coalition (AVAC, a front group for the HIV pharmaceutical industry), has expressed disappointment. One researcher is reported to have said "the failure of one method in one trial did not mean that the trial, or the idea of microbicides, had failed." Which is quite true. The failure could be for entirely different reasons, incorrect and unwarrented assumptions about the relative contribution of sexual transmission in serious epidemics being just one.

Treatment is Not Prevention, but it is Far More Lucrative

It's a relief to hear that there are some people working with HIV who are willing to speak out against the apparent assumption that treatment is prevention, that all we need to do is substantially increase the number of people taking expensive antiretroviral therapy (ART) for the rest of their lives, regardless of the known consequences of such a strategy, and HIV transmission will magically decline and eventually disappear.

Alison Rodger, Andrew Phillips and Jens Lundgren recommend that before adopting ART as a prevention policy, we need to assess the risk of HIV transmission through unprotected sex (ie, without a condom) when the viral load is undetectable. So far, research has revealed that transmission could be unacceptably high under such circumstances, but neither the media nor the academic hype around treatment as prevention has alluded to this.

Xiaohua Tao, Dan Shao and Wei Xue call for an assessment of how a policy of treating HIV positive people at an earlier stage of disease progression would affect their sexual behavior. They point to evidence that use of ART increases risky sexual behavior. They also express worries about the development of resistance to ART, which is one of the known consequences alluded to above.

Enthusiasts of the treatment as prevention strategy, Myron S. Cohen, Ying Q. Chen and Thomas R. Fleming, accept that the benefits of ART are unknown where condoms are not used as part of the strategy. They also note the frequent occurrence of pregnancy and sexually transmitted infections (STI) among trial participants, which suggests that self-reported sexual behavior was not so accurate, or that condoms are a lot less effective in reducing STI transmission and pregnancy than we are led to believe.

Essentially, Cohen and colleagues are a bit vague with one of the real worries about a treatment as prevention strategy: the lack of clarity about how HIV is transmitted so rapidly in only some countries. The orthodox view is that heterosexual sex is responsible for 80-90% of transmission. But why should a virus that is difficult to transmit through penile-vaginal sex be transmitted so rapidly in certain populations? Do they all secretly engage in anal sex? Or are there non-sexual risks that some of them face?

Uganda is an interesting case in point. The orthodoxy gather up lists of 'most at risk' people, men who have sex with men, intravenous drug users and the like. They also add in sex workers, truckers and other groups who are said to be vulnerable because of their 'mobility', whatever that may mean. But there is always the assumption that heterosexual sex is the key. Yet none of these circumstances explain massive rates of transmission in some countries, where most people don't fall into any of those groups said to face high risks.

Indeed, the majority of transmissions in Uganda and other countries are among people who do not face high risks, they fall into low risk categories, even by the strictures of UNAIDS and others in the industry. Don't these astute people notice the contradiction in their claims, that most HIV transmission occurs among low risk people, those who do not have high risk lifestyles? What is it about Ugandans? Is it their sex lives, their sex organs, or something else?

It's not just treatment as prevention or any other smug strategy that will fail if we don't make it clear how HIV is being transmitted, why it is being transmitted amongst people whose ostensible risk behavior levels are low and why doling out ever increasing amounts of drugs to ever increasing numbers of people should make any difference; because, so far, for every person put on drugs, two become newly infected. If putting 6 or 7 million people on ART doesn't reduce transmission, why should doing so with 16 or 17 million, or more?

Treatment is not prevention and until the actual modes of transmission, rather than assumed modes of transmission, have been properly assessed, HIV prevention efforts in Uganda and elsewhere will continue to be as unsuccessful as they have been so far. The fact that ART keeps HIV positive people alive does not mean that it will keep HIV negative people negative. It may help, but it is not enough.

[For more about non-sexual transmission of HIV through unsafe healthcare and cosmetic services, see the Don't Get Stuck With HIV site and blog.]

RETRACTION: 127 Zimbabwean Women Were Not Infected With HIV During Trial

Following an article in ZimEye.org, I mistakenly wrote that one arm of the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, involving the antiretroviral drug Tenofovir, was stopped because 127 women taking the drug became infected with HIV. In fact, these women were taken out of the trial because of 'futility', the finding that it would not be possible to show that the treatment they were receiving was more effective than the placebo that another group was receiving.

I apologise for reporting something so alarmist when the only source was an online article (which apparently also appeared in the Sunday Mail) that was released without any named author. I will take more care in commenting on such articles in the future. I have removed my blog post from the three sites where I placed it and will make the same efforts to publicize this retraction as I made with the original.

There will be a press release confirming the above, which I will post as a comment to this report as soon as it is available.

Give Them Pills: Wealth, Health and Education Will Magically Follow

A major worry about PrEP is not that it won't work, nor even that it may result in increases in 'unsafe' sexual behavior, but that it simply ignores the conditions in which HIV is transmitted. It's is a process of giving people drugs but leaving them in the very circumstances in which they are thought to be at risk from infection with HIV and various other diseases.

If people engage in high levels of unsafe sex, PrEP may result in increases in such behavior; or it may reduce such behavior, though claims that it does are probably wishful thinking. But PrEP is not designed to influence behavior, it's designed to protect people from HIV transmission, even if they still engage in risky behavior. If it was feasible to influence people's sexual behavior, PrEP would not be necessary.

So it may reduce the 'risk' of a HIV negative person becoming infected. But it doesn't aim to reduce their risky behavior. The same applies to treating HIV positive people with antiretroviral drugs regardless of the clinical stage they have reached, known as 'treatment as (or 'is') prevention', 'test and treat', etc; this also doesn't reduce their risky behavior, nor that of their partners.

Surely, if people face risks as a result of their sexual behavior, it is their sexual behavior that needs to be influenced, not just their risk of infection with one or two diseases? And if their risks are not just sexual, if they also face risks from unsafe healthcare or unsafe cosmetic practices, surely those also need to be addressed?

Because, even if massive increases in the numbers of people on antiretroviral drugs result, either because of PrEP, treatment as prevention or any other scheme or combination of schemes the pharmaceutical industry dreams up, such risks are not acceptable. They would also be far more cheaply and efficiently addressed in their own right, rather than by using a scatter gun approach using drugs alone. Nature and other commentators appear to be concentrating on commercial risks, while ostensibly worrying about potential failure of PrEP to reduce HIV transmission.

Attempts to influence sexual behavior have been very unsuccessful, but what about the need to influence (antiretroviral) drug taking behaviors and various other measures to reduce risk, for example, by using PrEP or treatment as prevention strategies? If people are not highly compliant, the drugs won't work and may result in increased rates of resistance, which can be transmitted from person to person, as well as developing in individuals on ARVs.

This problem is particularly acute in resource poor settings, where HIV transmission rates may be highest. UNAIDS claim that 80-90% of HIV in African countries is transmitted through heterosexual sex. But they have never said what it is about heterosexual sex in a few African countries that could result in massive rates of transmission.

How could putting millions of people on drugs be a substitute for explaining why Africans face such huge risks when there is no evidence that people with HIV engage in, or have ever engaged in, types of sexual behavior that would greatly facilitate HIV transmission?

Where would PrEP come in? By doling out drugs to every HIV negative sexually active person? And treatment as prevention? By doling out drugs to every HIV positive sexually active person? African countries have not even come close to getting all HIV positive people who have reached a specific clinical stage of HIV progression on antiretroviral drugs, without which they will die. What magic is going to put half or more of the populations of some countries on drugs?

Also, enthusaists claim that PrEP, treatment as prevention and other strategies are not just about drugs, that people receive a whole range of benefits, such as regular testing, counselling and various other things. But this is not true. For most high prevalence countries, being on antiretroviral treatment doesn't even guarantee the supply of drugs. Several countries have run out of drugs, some on more than one occasion. But most people on drugs get little more than drugs.

Mitchell Warren, director of AVAC, a pharmaceutical front organization that aims to increase the use of HIV drugs, at all costs it seems, is quoted, as usual. He says "We think of PrEP as a pill, but we all recognize that PrEP is about a much broader programme". Recognizing this is not the same as providing a 'much broader program'. So far, those who receive the drugs are lucky to do so and those who can also feed themselves and get hold of other treatment needs are luckier still.

As for the necessity to test people at two to three month intervals, which country has succeeded in testing all sexually active people once, let alone once every two or three months, or even once a year? Countries with high HIV prevalence tend not to have the health service capacity to do any of the things AVAC and other pharmaceutical flag wavers glibly take for granted.

Another article asks "Will healthy uninfected people consistently take an expensive and powerful drug that can cause a range of side effects?" But that question seems to be of secondary importance compared to questions about ignoring the direct risks people face as a result of their sexual behavior and the state of health care and other services in their country. The question also ignores the problem of identifying exactly who could benefit from these strategies in high prevalence countries and how those most in need would be identified.

Apparently proponents of PrEP have said it would be "unethical" not to explore its potential. Perhaps so. But a prior concern would be establishing exactly what risks people in high prevalence countries face, rather than assuming that the risks are all sexual. Otherwise strategies like PrEP and treatment as prevention will only serve the interests of the pharmaceutical industry. That's probably all the industry wants, but recipients of these drugs might require a little more.

Do High HIV Prevalence Countries Have the Resources for Test and Treat?

When the 'treatment is (or as) prevention' (or 'test and treat' and various other names) hypothesis was first mooted, some wondered how it would work. The plan is to test everyone in a population for HIV regularly and treat everyone found to be infected immediately, rather than waiting for them to reach a particular clinical stage. Adherents of the strategy have vaguely suggested testing 80% or so of a population but this has not been achieved in any high prevalenc country. But if such levels of testing are achieved, how often would testing need to be carried out, and what would be the feasibility of testing such large numbers of people that often?

These issues are still fuzzy. But recent research suggests that many people are unaware of their HIV positive status, even where high rates of testing have been achieved. According to Salim Abdool Karim, this illustrates "the need for frequent repeat testing and comprehensive prevention efforts".

Whatever 'frequent' testing means in high resource, low HIV prevalence countries, it seems an unlikely option in high prevalence countries, which are all poor. Health services are generally not able to cope with relative simple health conditions and in many countries are simply too expensive to afford or too distant to reach. Karim's study shows that rates of new transmissions, which are unbelieveably high in parts of South Africa, are also high among those who tested negative only a short time before.

Getting everyone to test once for HIV, even where 'everyone' means 80%, is hard enough, but getting them to test every year would be a whole lot harder. And every year is not enough in the South African study area in question. So test and treat still raises more questions than answers; are there any high prevalence countries that can meet the challenge of testing so many people so frequently?

Resolved: We Must Stop Ignoring Bloodborne HIV in Africa

Why do so many HIV-positive children in Africa have HIV-negative mothers?For example, approximately 30% of HIV-positive kids aged 0-11 years have HIV-negative mothers in Mozambique (see pp. 177-181 in: http://www.measuredhs.com/pubs/pdf/AIS8/AIS8.pdf).

Why are so many virgin men and women found with HIV? In the Republic of Congo, for example, virgin women aged 15-49 years have higher HIV prevalence than all women, 4.2% vs 4.1% (see p. 101 in: http://www.measuredhs.com/pubs/pdf/AIS7/AIS7.pdf).

The personal stories behind these statistics are hard to fit with the common view that almost all infections are from sex. Why has there been so little attention and response to Africans with unexplained infections?

THE PURPOSE OF THIS NOTE IS TO INITIATE DEBATE ABOUT WHETHER TO CONTINUE TO IGNORE NON-SEXUAL HIV INFECTIONS IN AFRICA. To do so, this note presents four arguments for AIDS activists, both in Africa and elsewhere, to recognize and respond to HIV from skin-piercing procedures in African health care and cosmetic services.

1. DE-STIGMATIZING HIV/AIDS: Programs for HIV prevention in Africa – including especially foreign-funded programs -- focus almost exclusively on sex. With all attention on sex, the emotions, prejudices, and controversies around sex naturally spill over into HIV programs. Thus, it is not only wrong to think that all African HIV comes from sex (see points 3 and 4, below), but also confusing and distracting. Currently, stigma against HIV is so great that most people with unexplained infections keep silent, so as not to be accused of sexual behaviors that some people don’t like. When the public discourse is corrected to recognize blood-borne as well as sexual HIV (see: http://dontgetstuck.wordpress.com), people with HIV from blood risks will be able to speak out without facing stigma compounded by charges they are lying. And they will then be able to contribute to public efforts to make health care and cosmetic services safe.

2. PREVENTING HIV INFECTIONS: Ensuring that medical facilities are safe will not only prevent HIV infection but also the transmission of other blood borne pathogens. Across Africa, HIV prevalence is lower in countries where more people are aware of blood-borne risks for HIV; see: http://dontgetstuck.wordpress.com/africans-aware-of/

3. SEX ALONE CAN’T EXPLAIN AFRICA’s HIV EPIDEMICS: All attempts to explain Africa’s epidemics as exclusively sexual have failed to find anything that is so different about sex in Africa that could account for Africa’s high rates of HIV prevalence. Studies find that Africans have fewer partners and use condoms more than Americans and Europeans.

Circumcision is less common in Europe than Africa. Sex can’t explain how HIV prevalence is lower after long term wars, and among people living further from health clinics. Sex is a risk for HIV because so many Africans are infected – but how are so many infected?  

4. EVIDENCE THAT AFRICANS GET HIV FROM SKIN-PIERCING EVENTS: A lot of evidence shows HIV transmission through skin-piercing procedures in Africa. Evidence is both old and new. For example:

(a) In 1985, Project SIDA in Kinshasa, Zaire (now the Democratic Republic of Congo), tested inpatient and outpatient children aged 1-24 months and their mothers for HIV. Seventeen (39%) of 44 HIV-positive children had HIV-negative mothers. Among children with HIV-negative mothers, “medical injections seemed to be the most important risk factor for HIV…” The study team noted, “Injections are often administered in dispensaries which reuse needles and syringes yet may not adequately sterilize them” (Mann et al, Risk factors for human immunodeficiency virus seropositivity among children 1-24 months old in Kinshasa, Zaire. Lancet 1986, ii: 654-7. p. 656.)

(b) Around 1990, WHO’s Global Programme on AIDS coordinated a study in Rwanda, Uganda, Tanzania, and Zambia to test in-patient children 6-59 months old and their mothers for HIV. Sixty-one (1.1%) of 5,593 children were HIV-positive with HIV-negative mothers; only three had been transfused. WHO experts concluded “the risk of non-perinatally acquired HIV and of patient-to-patient transmission of HIV among children in health care settings is low” (Global Programme on AIDS. 1992-1993 Progress Report. Geneva: WHO, 1993). A similar conclusion would be unthinkable if 1% of inpatient children in London, Boston, or Seoul were found with non-vertical HIV infections.

(c) A study among women in Malawi, 2003-05, found that women who had received hormone injections for birth control were 10.4 times more likely than other women to return with incident HIV infections, and 23 of 27 women with incident infections had received such injections; relative risk was adjusted for age, bacterial vaginosis, and number of sexual partners; reported condom use was uncommon for both women who acquired HIV infection (11.5%) as well as for those who remained HIV-negative (15.1%) (Kumwenda et al. Natural history and risk factors associated with early and established HIV type 1 infection among reproductive-age women in Malawi. Clin Infect Dis 2008; 46: 1913-1920).

(d) Many other studies in Africa link incident HIV to injections, report virgins with HIV, and report kids with HIV but HIV-negative mothers (see Chapters 7, 8, and 9 of Points to Consider, available for free download at: http://sites.google.com/site/davidgisselquist/pointstoconsider).

PROPOSAL: Let’s dialogue about this at these websites – http://aidsperspective.net/blog/, http://hivinkenya.blogspot.com/, http://blogs.poz.com/sean/, http://dontgetstuck.wordpress.com/ http://signpostonline.info/ – about the evidence, what to do, anything else relevant to the issue.


Simon Collery, David Gisselquist

Treatment As Prevention? Not By a Long Shot

There's an interview available with Myron Cohen on HIV treatment being a possible key to ending the pandemic. It would certainly be wonderful if existing drug therapies could reduce transmission enough for the pandemic to eventually be eradicated. Recent findings show that HIV positive people taking antiretroviral (ARV) drugs are less likely to transmit HIV to their partner. And there are good arguments for starting ARV treatment early, for the benefit of both the positive and the negative partner.

Frustratingly, the benefit of early treatment is highest for heterosexual couples. But the majority of HIV transmissions in the US are through male to male sex and intravenous drug use. However, the findings suggest that HIV treatment and transmission reduction is making a lot of progress in Western countries.

There is a somewhat different problem in African countries. Only a small percentage of HIV transmission is thought to come from intravenous drug use and men having sex with men, combined. And, according to UNAIDS, almost all HIV transmission is either through heterosexual contact or mother to child transmission.

It is clearly not feasible to put all people thought to be at risk of transmitting HIV on ARVs because the majority of them are not aware of their HIV status. And the stigma associated with HIV stems to a large extent from the view that it is almost always transmitted sexually. It means that every African, at least in high prevalence countries, is thought to be at risk, and mostly because of their sexual behavior.

Still, it would be interesting if UNAIDS were to rethink their attitude towards modes of HIV transmission, especially considering the orthodox view is not the result of any empirical investigations. Big Pharma could make a lot of money by persuading Western governments to use even more aid money to pay for drugs for HIV positive people. Global HIV policy would benefit from clarifying the relative contribution of various modes of transmission, sexual and non-sexual. Big money may work where the goal of reducing stigma, or even of implementing effective HIV prevention programs, hasn't.

The role of non-sexual modes of transmission, such as unsafe healthcare and cosmetic services, really needs to be questioned. Unless it is established how people are becoming infected, most prevention interventions will fail. Treatment may help with prevention, but it is not the same as prevention. It doesn't obviate the need to find ways of preventing HIV, however it happens to be transmitted.

Overall Benefits of PrEP as a Strategy Still Unclear

A trial comparing tenofovir microbicide with oral PrEP for HIV prevention is dropping the oral arm before the trial completion date. A monitoring board decided that it would not be possible to demonstrate any difference in effect between tenofovir PrEP and a placebo in preventing HIV infections. Other arms of the trial will continue.

Pharmaceutical industry front group AVAC's Warren Mitchell has expressed disappointment. But adverse publicity about PrEP is unlikely to be publicized as widely as the spin associated with favorable results, or results that can be dressed up as favorable. So far, it is the effectiveness of PrEP in preventing HIV transmission to women that is still in question. Women account for the majority of infections in young people in high prevalence African countries.

The HIV industry has still failed to show that PrEP, microbicide and various methods said to reduce HIV transmission do so in the specific case of sexual transmission. It is possible that drugs like Tenofovir also protect against non-sexual transmission, such as through unsafe healthcare and cosmetic services. But even if PrEP does protect against non-sexual transmission, it will not be the most appropriate strategy in these instances.

The best way to provide safe healthcare and cosmetic services is to ensure that strict hygiene and infection control procedures are followed, something the industry has long resisted. Separating any effect PrEP and microbicides may have on non-sexual transmission modes from its effects on sexual transmission modes would seem like a smart move. After all, there is little point in targeting populations who will not benefit from it; but nor is there much point in developing a strategy that is entirely inappropriate, even when that is where it may produce the best results.

The trials, the wishful thinking and the spin continue.

Health in Africa: Always a Crisis, Never a Priority

Tanzania and Kenya are both issuing warnings about 'fake' and unregistered drugs. Unfortunately, many people have been led to believe that 'fake', 'generic', 'counterfeit' and even drugs with 'Made in China' on them are all the same; useless. The chances of protecting people from substandard drugs, out of date drugs, those with the wrong ingredients, those with no active ingredients or those with the wrong quantities of ingredients, etc, is now seriously diminished.

The pharmaceutical industry, not short of a few billion dollars itself, wants regulatory authorities and others to protect the industry's profits, so they are in favor of such scare tactics. But they have brought about the situation where people will produce their own versions of drugs and create a thriving black market. Big Pharma has failed to produce drugs at a price that is affordable to those who need them most.

I suppose I have to spell it out that I don't think there's anything wrong with making a profit. But many drugs are developed using public money, in publicly funded institutions. The cost of researching drugs, which is very high, is not entirely borne by the industry. Only the profits are entirely borne by the industry. And the same industry often spends many times more on advertising, lobbying and marketing than they do on research.

There really is a problem with drug supply in East African countries; there are too few of them, many are of the wrong kind, some are fake or counterfeit. But some are generic, that being the best that people in developing countries, the majority of people in the world, can afford. And all drugs, even generic drugs, are overpriced. There is still no true competition, where prices are set according to what the market can bear rather than what the over-subsidized industry can grab.

Pharmaceutical outlets, even many health facilities in East Africa, can be badly run, semi-formal, informal or downright illegal, and are in bad need of regulation. But running around closing them down or curtailing their activities will do little good unless proper facilities are made available to people. The lion's share of health spending in East Africa goes into the pockets of Big Pharma, mostly for branded drugs and products developed with Western needs and economies in mind. There's no shortage of money.

Unsafe drugs are only one of the many risks that East African people face in pharmacies and health facilities. The priority is to improve conditions in these facilities and increase people's access to them, not to increase the amount of donor and public money that helps inflate pharmaceutical industry profits. Drugs are only a part of health care, but only when there are adequate health facilities with enough well trained and equipped staff. Stop using aid money to support pharmaceutical multinationals!

[For more about unsafe health care and cosmetic services, visit the Don't Get Stuck With HIV website]

Drug-Based HIV 'Prevention' Strategies Alone Will Fail

While about 25% of HIV postive people in the US and the UK are thought not to know their status, only about the same percentage of people in some African countries are aware of their status. Many years of testing campaigns are only changing that figure slowly. But the pace of development in pharmaceutical products and treatment practices available is way ahead of the testing campaigns. Marketing and media campaigns are similarly ahead of the game, ahead of the evidence, some might say.

PrEP has been undergoing various trials for quite a few years now, but it has not yet shown itself to be the most appropriate strategy in countries with high HIV prevalence rates. Even 'test and treat' ("testing all adolescents and adults annually for HIV infection and immediately treating those found to be infected") may sound good on paper; but it will struggle to prove itself as a strategy in less well off countries.

Test and treat would work best if it could catch new HIV infections at the earliest clinical stage, during which it is most likely to be transmitted to others. But if far less than half of the HIV positive people know their status, the chances of a substantial number of early infections being identified are small. It is more likely that most infections will continue to be identified when people have been infected for many years, even at the latest stage of infection (which is often far too late).

If the plan is to test sexually active people every year, this will involve a huge scaling up of current testing practices and a massive change in the testing behaviors of the entire population of quite a number of poor countries. One might even ask if testing sexually active people once a year is enough, given that 'early stage of HIV infection' means the first six months. (Testing at least every six months is estimated to be required by the author of the above article.) But this must be compared to the consideration that the majority of people in African countries have never tested; many of those who have tested only did so once.

Like PrEP, test and treat seems suspiciously passive, as if we are waiting till lots more people become infected and then treating them with the ostensible aim of preventing further infection. In conjunction, these strategies will be great for pharmaceutical company profits, there's no question about that. But as to whether they will cut infection rates substantially, there is plenty of room for doubt. Early initiation of antiretroviral therapy (ART) has also been pushed as a highly beneficial strategy, but the evidence is not yet convincing.

These three strategies (PrEP, test and treat and early ART initiation) are a little like prevention of mother to child transmission (PMTCT) in that they require at least one infection in order to 'protect' some unknown number of infections in the future. The percentage reduction in mother to child transmission gained through use of PMTCT is, of course, well established. But brilliant levels of PMTCT rollout, and it is by no means widespread in many of the highest prevalence countries, is puny when compared to low HIV prevalence among young women, pregnant women and mothers.

South Africa has the highest number of HIV positive people in the world, over five million. The majority of new infections are occurring in young women. To the best of my knowledge, no large scale effort has ever been made to asses the sexual and non-sexual HIV risks that these women face. The view that they are almost all infected through heterosexual behavior is still just an assumption, albeit one supported by almost every HIV academic currently writing. If there are HIV positive people infecting these women, find them. They also need treatment, more urgently than anyone else.

This is not a call to increase the levels of anti-African prejudice that UNAIDS and the HIV industry currently enjoys; it is a serious suggestion that sexual partners of young HIV positive women be identified. Many South African men, young and old, will be found to be HIV negative. The same would be true of men in other high prevalence African countries. Therefore, young women's non-sexual risks also need to be identified.

The above HIV drug-based strategies center around the belief that HIV is almost always transmitted through heterosexual sex and almost never through any non-sexual routes, such as unsafe medical or cosmetic services. If these assumptions turn out to be false, the above strategies will cease to appear so tempting.