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.