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by the US Food and Drugs Advisory for possible production by 2014 that we heard so much of just a year ago has been replaced by the kind of silence we've come to expect from results that can't even be dressed up to look a little bit positive.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.