Truvada and Tenofovir PrEP Trials Continue in Kenya Despite Setbacks

There are still PrEP trials going on in Kenya, this time among 4,800 discordant couples in the Thika area. The work is partly funded by the Gates Foundation, which is not surprising. But one of the findings in the shelved FEM-PrEP trial was that more women on the drug became pregnant than those on the placebo, despite all women taking some kind of contraceptive as a condition of the trial.

Increased fertility will not please either FHI, the institution running the FEM-PrEP trial, not the Gates Foundation, as both are firm believers in the assumption that development is a matter of population control, something that used to be called 'eugenics'.

Although antiretroviral (ARV) industry front group AVAC are trying to paint a rosy picture of PrEP, FEM-PrEP wasn't the first disaster. The iPrEx trial results were far too poor to allow further trials to proceed without extreme caution. Despite that, some groups are calling for approval of the use of Truvada as PrEP to be fast-tracked by the US Food and Drug Administration (FDA).

[For more about HIV and development, see my other blog.]

AIDS Healthcare Foundation Are Right to be Cautious

The AIDS Healthcare Foundation (AHF) are a good friend to Western gays but Western men who have sex with men (MSM) seem to think otherwise. Gilead's Truvada, was found to be 44% effective in preventing HIV transmission in MSM in the iPrEx trials. This result means that the drug would be of marginal benefit, at best, outside of trial conditions. At worst, HIV transmission rates could stay the same or increase.

All AHF are saying is that FDA (US Food and Drug Administration) approval for use of Truvada as pre-exposure prophylaxis should be delayed until it is fully understood why effectiveness is so low and what sort of value this use of the drug has, if any. Do Western MSM wish to be guinea pigs in what would merely be a re-run of the trials but under less favorable conditions?

The FEM-PrEP trial of Truvada as pre-exposure prophylaxis for women engaging in (presumably vaginal) sex with men showed no effectiveness whatsoever in reducing HIV transmission. Most of the study participants were women in African countries, and perhaps Western MSM are not so worried about this group. But AHF are drawing attention to the fact that it is far too early to give the drug approval. They are not saying it should never get approval.

In areas where HIV transmission is phenomenally high, such as in the study areas, entire sectors of the female population are being infected. And even after these supposedly controlled trials, research doesn't appear to have shown why women are being infected in such large numbers, especially when their sexual behavior is similar to that of women in low prevalence countries and the men they are having sex with are far less likely to be infected.

If you don't know how people are being infected, throwing drugs at them will not solve the problem. Gilead may be able to increase their profits by a billion or more, but the HIV industry wasn't established to make wealthy and powerful pharmaceutical companies wealthier and more powerful. If and when PrEP is able to show its value in reducing HIV infection, it should be considered for approval. But it has not yet shown its value and the HIV industry should distinguish between who is suffering from the effects of AIDS and who is profiting from it.

[For further comments about PrEP, see my other blog.]

Unbelieveably High Adherence Doesn't Guarantee Effectivenss of Truvada

A less well publicized trial of Truvada for pre-exposure prophylaxis has finished early. Not only is it less well publicized, but the results are not being released in full until further notice.

Family Health International's (FHI) press release said "the Independent Data Monitoring Committee (IDMC) advised that the FEM-PrEP study will be highly unlikely to be able to demonstrate the effectiveness of Truvada in preventing HIV infection in the study population."

This trial was like the iPrEx study except that it was testing the use of Truvada to prevent HIV infection in women. The release of preliminary data only contrasts strongly with the way iPrEx data was released, even though the latter data was not particularly impressive.

Adherence appears to have been extremely high, higher than in the iPrEx study. But the rate of new infections was very high, at 5% per year, and there was not difference in rate between those on Truvada and those on a placebo.

Interestingly, 66% of women were using injectible contraceptives. This a popular contraception method in many African countries. Unsafe injection rates, which are extremely high in developing countries, might explain at least some of the transmissions.

Higher pregnancy rates were found among women who were taking Truvada and this was quite unexpected. It's good to hear that researchers and other commentators are being cautious, unlike with the iPrEx trial results.

PrEP Should Never Be First Line of Defence Against HIV

There's an interesting exchange that I heard about through JournalWatch. Readers of HIV/AIDS Clinical Care journal were asked if they would prescribe PrEP for a high-risk patient. Remarkably, 45% said they would not. More surprisingly, 35% said they would prescribe PrEP intermittently, surprising because this is not a currently recommended use. Only 20% said they would prescribe daily PrEP, the only use that is  currently available.

But two detailed responses outline what the practitioner would do, step by step. And it is these steps that makes me wonder what form PrEP prescription would take in developing countries, where most people are unlikely ever to see a doctor.

Those with only vague notions of what PrEP is, anyone who has been informed by following the mainstream press, might think it is a pill that you can take to prevent yourself from being infected with HIV. In fact, it's a pill that may play some small part in reducing the probability of infection if you also take other precautions, such as always wearing a condom, reducing your number of partners, etc.

As one of the practitioners says, PrEP "should never be the first line of defense against HIV infection". The same practitioner says "the healthcare system [in the US] currently lacks the infrastructure to support PrEP care in the manner recommended by the CDC". Whatever Western health infrastructures lack, they sure as hell will not be found in developing countries.

But there is a sort of paradox about behavioral interventions that aim to reduce HIV transmission: PrEP depends on strict adherence, which is a behavioral matter. Whether someone is considered to be at high or low risk of HIV infection is based on their behavior. If their behavior is tractable, their risk can be reduced. If their behavior is not tractable, their risk can not be reduced.

So, if someone is the sort of person who would adhere strictly to a PrEP prescription, they would be likely to benefit from PrEP. But then they would be unlikely to be at high risk of infection. But then a person would be unlikely to be able to benefit from PrEP if they are genuinely at high risk of infection because of their behavior.

Perhaps a partner of someone whose sexual behavior puts them at high risk of HIV infection could benefit. They would need to take other precautions aside from PrEP, otherwise it is unlikely to give them much protection. But penile-vaginal sex is not particularly high risk, so PrEP is unlikely to be the intervention of choice anyway.

Will Profits From the HIV Pandemic Ever Be Accompanied By Progress?

The answer to the question 'will Africans most in need of PrEP be able to access it?' is not a straightforward yes or no. If the question were 'will Africans in need of the most common and effective drugs for the most common, treatable, preventable and deadly diseases have access to them?', the answer is 'they certainly don't have access right now'. So why should we believe they will ever have access to PrEP?

But the question is harder to answer than that. Even if the HIV industry were to wave a magic wand and grant PrEP to whoever needed it most, they have no idea who those people would be. They don't know who is at most risk of HIV infection or of transmitting HIV and they have never known. Or they have never been quite frank about it.

There are Modes of Transmission Surveys, but these are figures cobbled together from a disparate collection of assumption, guesswork, prejudice, overactive imagination and devotion to the tooth fairy. In the end, some Africans are more likely to be infected than others, but those the industry says are most likely to be infected are not the most likely, or they are not likely to be infected for the reasons the industry says.

The majority of infections in East African countries are in married couples and those in long term relationships. Many of these people are not promiscuous, many only have sex with their partner, they don't have sex very often and many of them even take precautions to prevent infection with HIV, other sexually transmitted infections and unplanned pregnancies. In other words, a disease that is difficult to transmit through any kind penile/vaginal sex is commonly transmitted through low-risk heterosexual sex.

An update from a recent conference doesn't mention the above issues. It is accepted that effectiveness is only moderate. But there is a tendency to believe that adherence will, almost miraculously, become better than anything every seen in the history of healthcare that focuses on technical fixes.

One only need look at the number of HIV positive people who die without treatment, the number who die on treatment, the number whose treatment has failed and they are seriously ill, the levels of resistance that are mounting up over the years, etc, to wonder where all the optimism about PrEP comes from. It may be great, but will it have a great impact, or any impact, where it is most needed?