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?

Maximizing Profits from a Drug that Doesn't Work

Advocates of PrEP are probably as aware as anyone else that it hasn't yet shown much promise for men who have sex with men (MSM). It may not even be of much use in combination with other strategies (that also haven't shown much promise). But no one really wants to be the first to say that there is still a lot left to do, or admit that PrEP may end up in the broom cupboard.

Advocates still go back to their tack of 'sub-group analysis', taking the group that shows the best level of adherence to the drug and pointing out how effective it was for them. But high levels of adherence to PrEP could indicate other protective and risk avoidence practices, so care needs to be taken in interpreting this.

More importantly, levels of adherence in the group that shows the lowest levels of adherence could indicate that they engage in other risk behaviors and fail to take protective measures, adhering to PrEP just being one. Dr Joseph Sonnabend has discussed the folly of such analyses.

So these advocates of PrEP gathered around the ashes to figure out what to do and one of the questions they came up with was "what subset of men would be the most appropriate candidates for this new prevention tool?" Sonnabend's warning against sub-group analysis recommends an 'intention to treat analysis' as an alternative.

However, PrEP on an intention to treat basis would mean they would aim to put all MSM on the drugs. And then you have the problem that you will spend a lot of money for a miniscule return (if any). Even UNAIDS will start to notice if the effectiveness of PrEP doesn't improve considerably.

The group of advocates conclude that "PrEP is not a “magic bullet” and that it should not be viewed as the sole approach to reducing new HIV infections among MSM".

Exactly; they've also got a brand new roll of sticky tape, a stapler, a needle and some thread, a pot of glue and some thumb tacks, otherwise known as 'treatment 2.0'. So maybe they won't need the PrEP after all.

Is Most HIV Spread By Sex? No, But Billions of Dollars Say Otherwise

Most of the billions of dollars currently being spent on HIV go to treating and caring for those already infected. A small amount is being spent on 'preventing' HIV but most of that is targeted at sexual transmission, despite the evidence that this is not the only type of transmission. It may not even be the most common type of transmission.

My remarks apply to African countries because that's where HIV epidemics are worst, where most HIV positive people live and where most people at risk of being infected live. It's where HIV, rather mysteriously, almost always spreads through heterosexual sex, while everywhere else in the world it mainly spreads through anal sex and injecting drug use.

One third of research and development funding for over 30 'neglected' diseases is spent on HIV, according to the G-Finder report by Policy Cures, an 'independent' group that happens to rub shoulders with some of the top HIV industry and pharmaceutical players. None of the money spent on HIV R&D is being spent on nosocomial or iatrogenic transmission, transmission that occurs as a result of unsafe medical treatment. HIV drugs, whether they are pre-exposure prophylaxis (PrEP), microbicides, vaccines or antiretrovirals, are aimed at sexual transmission.

In fact, HIV, TB and malaria R&D funding accounts for more than two thirds of all funding, amounting to over two billion dollars a year. Conditions that maim and kill millions of people every year, such as water-borne and food-born conditions, only receive a fraction of this amount. (Although it's interesting to note that the authors of the report are aware of the significance of diarrheal diseases.)

As for provision of clean water and sanitation which would reduce incidence of all of these conditions, this is not even discussed in polite circles.

Developing health services and facilities is not much discussed either. Pharmaceutical and other companies competing for billions of what is, after all, public money, know that if money was spent on health services and facilities and improving access to them, they would end up with far fewer customers.

So, there is no evidence that HIV is almost always transmitted sexually, even in African countries. But an awful lot of money is being spent on 'preventing' sexual HIV transmission while next to none is being spent on non-sexual transmission. And being able to talk about sex and promiscuity is quite a blessing for an otherwise sterile industry. So don't expect attitudes to change quickly.

[For more about nosocomial and iatrogenic HIV transmission, see my other blog, HIV in Kenya.]

Your Solution Is The Problem, Mr Gates

Bill Gates seems to write at least some of this own materials. His 'annual letter' reads as you'd expect it to read if written by someone who has little understanding, of and probably little interest in, development. His priorities are high profile issues and his 'solutions' are high technology and narrowly focused. But development issues and appropriate measures to improve conditions are not isolated phenomena, they also have a context.

Gates' grasp of public health is particularly weak. He seems to think that a handful of diseases can be eradicated, without any attempt being made to improve the conditions that result in those diseases remaining widespread, often after decades of work and billions of dollars spent. He wants to eradicate polio and prevent cholera, for example, without ensuring that people have access to clean water and sanitation.

An article in Science and Development Network picks up on Gates' comments about the 'slow pace of progress' in fighting AIDS. In the case of treatment and care for HIV positive people, he probably has a point, although he seems to think this area is doing well. Yet, in high prevalence countries, only a minority are receiving the care they need and most of them are lucky to receive drugs, which are of limited value on their own.

The pace of progress in HIV prevention is even more lamentable, but I don't really see Gates and his Foundation doing much about it. He seems to think that if drugs and a few other things rain down from the heavens, everything will be fine. He doesn't seem to see the need for health facilities, trained personnel, equipment, processes and other supplies.

This naivety might be touching in someone who is still growing into such a role as his. But given the extent to which he and his Foundation skew global health, development and spending priorities, treating his word as gospel is downright foolish.

The fact is, Mr Gates, most deaths among HIV positive people in developing countries are preventable and treatable. Most of the people who are dying should not be dying. They die because developing country health services can barely even dole out the antiretroviral drugs they are given in such huge quantities (sometimes), while they don't have the cheap drugs they need to stop people from dying from diseases the Gates Foundation doesn't consider worth bothering about.

But Gates still reverts to his obsession, drugs, in the form of vaginal microbicides and PrEP. We've tried forcing drugs down the throats of HIV positive people, lets now try to force them down the throats of HIV negative people as well. Oh, and he wants a vaccine as well. And male circumcision.

Money is not going into investigating how people are becoming infected with HIV. It's assumed that sex is the problem and drugs are the solution. Health systems just don't seem sexy enough to merit attention, nor do improved infrastructures, water and sanitation, basic education or anything else that might alleviate the conditions that allow HIV to spread rapidly.

Gates said "given all the lives that are at stake, I am willing to be viewed as a troublemaker by people who are happy with the status quo". Sorry, Mr Gates, but you are the status quo in development, Indeed, that's what makes you a troublemaker.

In Case of Poor Health, Treat for HIV

Dr Joseph Sonnabend has a fascinating article on his blog about the original AZT trials, which notes that in the 1980s, many people with AIDS were dying of pneumocystis pneumonia, a preventable and treatable condition. That was in the US and other wealthy countries. But I suspect similar things are still happening in developing countries.

For example, sixty percent of people living with HIV in India are said to be dying of TB, a disease for which there are ample tests and drugs available. Dr Sonnabend notes a defeatist attitude in the 1980s but I don't think that attitude has lessened in resource poor countries.

In some countries, mothers are routinely treated with antiretroviral drugs to prevent transmission to their babies. But the health of the mothers themselves if often seen as being of little value compared to the life of  their babies.

HIV positive mothers who give birth to HIV negative babies are not likely to be seen as a priority and may become sick and even die from preventable and curable illnesses. And if mothers die, the chances of their children suffering ill health and even of dying are significantly raised. Prioritizing the needs of their babies and ignoring the longer term needs of their mothers is extremely short sighted and even self-defeating.

In Kenya, I met a number of HIV positive people who subsequently died from TB or from undiagnosed conditions. AIDS was always blamed, but the people who died were usually on antiretroviral medication. Just because they were HIV positive, it was assumed that they were going to die and when they became very ill, there was often little available to them that they could afford.

Many of them had TB, which was sometimes being treated. But even people with TB are assumed to be HIV positive, although only about half the Kenyans with TB are also HIV positive. There is little said about the massive TB epidemic raging in Kenya, unless insofar as it is associated with HIV. But it's a very easily transmitted disease and it appears to spread independently of HIV just as efficiently as in conjunction with it.

The article about India continues: "though we have 12,500 microscopy centers available across India, deaths occur mainly due to late diagnosis, owing to technology limitations". In Kenya, the problem may be due to factors other than late diagnosis, for example, lack of facilities for diagnosis, lack of access to health facilities and lack of drugs for even very common conditions.

Distribution of HIV technologies always seems to have a lot more to do with markets than about need. And when all you have is a hammer, everything looks like a nail. There seems little point in treating people with expensive antiretroviral drugs and allowing recipients to suffer from and die from preventable and treatable conditions. But who am I to tell drug manufacturers how to maximize their profits?

[For more about HIV and health care, see my other blog, HIV in Kenya.]

If You Need PrEP, You Probably Won't Receive It

Although not yet approved for use as a pre-exposure prophylaxis for men who have sex with men, CDC has issued guidelines for its use, a sort of de facto approval. But the guidelines make it clear that this is an expensive drug, intended for recreational use among those who can afford it. It's certainly not for people who live in the handful of African countries where HIV prevalence rates are the highest in the world.

For example, confirming that someone is at "substantial, ongoing, high risk for acquiring HIV infection" is going to be a bit of a challenge for the UNAIDS dominated prevention strategies in developing countries. As far as they are concerned, if someone is African and has sex, they are at high risk. The majority of infections occur among those engaging in what is essentially low risk sex. The contradiction doesn't bother UNAIDS.

Regular testing for those on PrEP is out of the question for most people in countries where most people are never tested and HIV positive people usually find out their status by the time their problem is AIDS rather than HIV. Similar remarks apply to regular sexually transmitted infection testing; poor countries don't have the health infrastructure to do this sort of work on large sectors of the population, even if they could identify which sectors those happen to be.

And so on. The measures recommended by CDC are pie in the sky for developing countries, where HIV prevalence wouldn't be nearly as high if they had such strong health services. And as for the remarks about adherence, the trial results cited completely fudge this issue. The overall 44% lower likelihood of acquiring HIV is constantly qualified by the higher figure achieved by those with high levels of adherence.

How about the lower figure for those who achieved the lowest level of adherence? People who fail to adhere to drug regimes or other measures that are intended to reduce risk of contracting HIV and other diseases are the very people who are at the highest risk. In other words, those least likely to adhere, and therefore to benefit from Truvada PrEP, are the ones who should be targeted. That's according to the guidelines, anyhow.

African populations are handy for testing out HIV drugs because there are very high levels of HIV transmission in many areas. But this drug is not intended for them. It is intended for those who wish to continue having risky sex but to minimize the risk of contracting HIV. The less risk they take, the better Truvada will work, but the less they will need it. The more risk they take, the worse Truvada will work and the more they will need it.

Mixed Messages From CDC for Men Who Have Sex with Men

Apparently only 'high-risk' men who have sex with men should use Truvada as pre-exposure prophylaxis. Who are these high-risk men but those who tend not to take precautions? PrEP, if it works, is a precaution. Therefore, the only people likely to take PrEP as recommended would be considered to be low-risk.

But is Truvada really intended for those men who have sex with men who are at highest risk of HIV infection? I don't really believe that. I would suggest that Gilead, the manufacturers of Truvada, intend to break into the recreational drug market. I'd say they want people who don't wish to use condoms to use PrEP instead. I think that's what the whole pharmaceutical industry wants.

The US Center for Disease Control (CDC) has not approved the drug for preventive use. Yet they issue guidelines for its use as PrEP. Anyone can use Truvada if they can get hold of it and any doctor can prescribe it. I think we can be fairly certain that it will be prescribed and used as PrEP, as a recreational drug.

After all, people who are at high-risk of becoming infected, well, take risks. CDC not approving it as PrEP, but issuing guidelines, is not going to make people think twice. And whether Truvada results in "78% fewer cases of HIV infection" or reduces "infection by 44%" will make little difference to those who may already be engaging in have unprotected anal sex.

CDC and others are giving mixed messages and they seem to be doing so knowingly. If people listened to advice, they wouldn't be at high risk of being infected with HIV. Therefore, I suspect this whole scenario is calculated to maximize profits and minimize risk for the pharmaceutical industry and has little to do with the risk of contracting or transmitting HIV.

Is PrEP Destined to Be a Recreational Drug for Westerners?

There's a lot of excitement, not so surprising, about the results of a PrEP trial which took place among gay men and transgender women; it can cut new infections by at least 44%, those carrying out the research say. Thankfully, there are also cautioning voices, suggesting that there is a long way to go and that 44% in ideal conditions may not translate into 44% in non-trial conditions, the above article being one of the cautioning voices.

Presumably timed to coincide with World Aids Day on the 1st of December, this good news is likely to dominate the headlines for some time to come. I needn't go through the ins and outs of the trial, they are widely available. And there are even some good critiques that raise questions that need to be asked about an approach to a disease that depends entirely on some drugs.

Technologies such as antiretroviral treatment (ART) are great when they are used to prevent and treat a virus like HIV.But something that bothers me about HIV drugs is that the, arguably more important, objective of preventing HIV transmission by finding out what its determinants are and mitigating them has long gone out the window.

I have argued elsewhere that a significant amount of HIV transmission comes from unsafe medical practices. The WHO estimates a figure of 260,000, likely to be on the low side. No drug is required to prevent this so-called nosocomial (or iatrogenic) transmission of HIV. All that is required is good, affordable healthcare.

But there doesn't seem to be much appetite for providing people with what they really need. Single diseases have always had greater appeal and the exaggerated association of HIV transmission with sex continues to make it the biggest single recipient of health funding ever.

Sean Strub has an interesting article on post-exposure prophylaxis (PEP), antiretroviral drugs used after a suspected exposure to HIV has occurred. He has found that many people who should know about PEP don't. Although it has been widely available to healthcare workers in wealthier countries, and ostensibly in poor countries, it is not promoted widely enough among the many people who may face similar or even higher risks.

[For more information about PEP, have a look at the PEPnow site.]

I have talked to a lot of people in Kenya and Tanzania who should know about PEP but don't. This is inexcusable because PEP has been available for many years. But the fact that it is nowhere near as well known as it should be suggests to me that the current enthusiasm for PrEP is not because it could reduce and perhaps eventually eradicate the virus.

The fact that 'we' or 'science' or 'technology' can do something does not mean it will be done. 20% of deaths in under fives could be prevented by provision of clean water and sanitation, another 20% are caused by easily preventable and treatable respiratory infections. The vast majority of maternal deaths are also preventable.

Dare I suggest that developers of PrEP are more interested in the 'recreational' drug market? Something to reduce the risk of contracting HIV without the need for condoms or other precautions, perhaps?

Will People Use Condoms With Pre-Exposure Prophylaxis or Microbicides?

A trial of combined condom and diaphragm use found that, although condom use increased during the trial, it returned to pre-trial rates afterwards. A commentator notes "What happens after trials has always remained very much a mystery". This appears to be true, and it's very disturbing.

Trial conditions are very different from non-trial conditions. Strict protocols are observed, at least in theory, so one would expect behavior to be substantially different once the intervention in question moves into the field. Especially when the trials show that the intervention only produced a small or temporary change in behavior. But results may even be a mere artefact.

Results of trials of mass male circumcision, microbicides (such as the tenofovir based gel tested in the CAPRISA trial), pre-exposure prophylaxis, test and treat strategies and other approaches to HIV prevention, which depend on the possibility of influencing sexual behavior, all share the risk of being artefacts.

Ariane van der Straten was involved in the Methods for Improving Reproductive Health in Africa project. This showed that, in many areas, the interventions involving diaphragms and lubricant, in addition to condoms and counselling employed for the control group, resulted in slightly higher rates of HIV transmission. However, the differences were not statistically significant.

Van der Straten points out that "it is a challenge to use concurrent HIV prevention methods, particularly barrier methods". All the technical solutions mentioned above require people to continue using condoms, even after circumcision and/or using microbicides or taking pre-exposure prophylaxis. Does she mean 'it is a challenge' or 'it is probably inadvisable'?

The study emphasised an unmet need for birth control, but this is hardly a surprise.

Van der Straten's concluding remark is particularly related to one of the assumptions about microbicides, though it may apply equally to pre-exposure prophylaxis. That is the claim that they are 'female-controlled'. Van der Straten says "In the past we have been naive, thinking that female-controlled methods could be used independent of men's involvement, but it's difficult to use any of these methods secretly, so there is a need to involve male partners in female-controlled methods so that they support their partners".

The full report is also freely available online.

Dear CAPRISA 004, You've Been Dumped

The most hyped issue by far at the hype-laden Vienna Aids Conference a few months ago was the CAPRISA 004 microbicide trials, which is said to be "at least 39% effective in preventing HIV infection" when applied before and after sex. There were calls for the technology to be made widely available as soon as possible, though the trial results are not impressive and several more years, at a minimum, are required before a viable product results.

On the strength of the hype, attempts were made to raise $100 million to carry out further trials. But only $58 million has been raised so far. What has happened to all the enthusiasm of a few months ago? Given his endorsement of technological fixes, especially pharmaceutical ones, why hasn't Gates coughed up the shortfall yet? And why is so much of the money coming from donors? Big Pharma constantly bleats about how much money they invest in products as an excuse for extorting enormous profits out of what is often publicly funded research. Where are they now?

Many African countries are finding just how quickly donors pull out when it suits them, although these countries were heroes in the fight against HIV only a short time ago. Far fewer people receive antiretroviral drugs than need them, many of them are lost to follow up, develop resistance, die of something curable or simply cease to be important now that HIV treatment on its own is no longer flavor of the month.

What could explain this sudden lack of interest? Will PrEP experience similar fluctuations?