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.

PrEP: How Many Lightbulbs Does it Take to Change a Prejudice?

One of the biggest puzzles that the HIV industry hasn't answered is that it is mostly intravenous drug users and men who have sex with men who are infected with HIV in Western countries, for example, the US. But it is mostly heterosexuals, the majority of whom don't engage in particularly risky behavior, who are infected in African countries. This is a potentially huge problem for PrEP (pre-exposure prophylaxis).

There's a rather smug article on Drugs.com entitled "HIV Experts Create the Roadmap for Providing PrEP to Uninfected Individuals to Reduce the Risk of HIV Infection". But the remarks in the article, while possibly relevant to those in Western countries, seem to have little relevance to people in the highest prevalence countries. That's not unusual in articles about PrEP and HIV drugs in general, but it doesn't inspire confidence in these 'experts'.

Firstly, it is not possible to target those 'most at risk' if you don't know who they are. Most new infections in African countries are not people who could be considered to be taking a lot of risks, not sexual risks, anyhow. Take, for example, Uganda. Most new infections are among those in long term relationships, a good many of them are not promiscuous and a good many have partners who are HIV negative.

Secondly, if the risks people face are not sexual, PrEP may not be the most appropriate prevention strategy. It's obtuse to prescribe PrEP to someone who is at risk of being infected at a dental clinic, in a hospital or at a tattoo parlour. And there are far more effective and cheaper options.

If the industry doesn't accept that people face non sexual risks they will fail to protect those who are genuinely at risk. Even those whose main risks are sexual will also probably be missed out. Because of the stigma attaching to HIV where heterosexual sex is said to be the main problem (as is the case in Africa, but not elsewhere), people don't wish to be tested, to talk about their status or to even face the possibility of infection in others.

PrEP is unlikely to be the most appropriate pretection from HIV infection for intravenous drug users, either. It would be far cheaper and more effective to provide them with counselling and supplies of clean injecting equipment. But as with men having sex with men and commercial sex work, criminalization ensures that those at risk are unlikely to come forward and unlikely to get the treatment they need if they do.

If and when prep is to be considered in developing and high HIV prevalence countries, both sexual and non-sexual risks will need to be assessed. This is something that is not currently done, though it should be. Otherwise, the strategy is likely to be of little benefit and may do a lot of harm. Anti-African prejudice in the HIV industry is not often discussed, but it is in danger of scuppering their current favorite 'game changer'.

Public Funding Disappears into Private Black Hole

Burundi is not the first African country to run short of antiretroviral drugs and it is unlikely to be the last. Apparently, the shortage has already been blamed for 20 deaths. Only just over 40% of Burundians in need of the drugs are currently receiving them. In addition to sickness and death, shortages of the drugs can give rise to resistance to the only antiretrovirals that are affordable to Africans.

The shortage is attributed to a serious drop in donor funding. But even a change in emphasis in donor funding could have a similar effect, for example, if it were decided that PrEP for HIV negative people could compete with ARVs for HIV positive people in the race for funding.

Meanwhile, other research shows that earlier treatment may result in reductions in HIV transmission. The claims made about the effectiveness of earlier treatment (and more people treated) are controversial because they are based on a best case scenario. However, pharmaceutical industry mouthpieces such as AVAC are playing down any possible worries that may be raised by a fairly compliant HIV industry, led by UNAIDS.

According to the head of UNAIDS, Michel Sidibe, 'treatment is prevention', a favored soundbite of the industries that stand to profit most from the HIV pandemic. Which competing interests will be benefiting from dwindling funds is not clear, though it is unlikely that any of the current beneficiaries will be any less well off.

Interestingly, the EU is busily trying to scupper any chance that drugs, formerly unaffordable to everyone, still unaffordable to those in high prevalence countries, might one day be priced at a level that can allow all those who need them to afford them. The EU wants India, the producer of the cheapest generic drugs, to sign an agreement that will prevent them from continuing to do so.

Sidibe also makes a common claim about HIV funding, which dwarfs funding for all other health areas in developing countries: he tries to include other diseases such as TB along with HIV as a possible target of the funding. However, there is a serious TB epidemic in many African countries that is quite separate from HIV, though the two overlap somewhat.

TB is another disease where drug resistance is a very serious problem, probably because it is targeted in  relative isolation from other diseases and from the conditions that give rise to serious epidemics and health problems. But it also makes a lot of money for the pharmaceutical industry and is likely to be a significant cash cow in the future.

I guess we should never expect public money for health or human rights to be prioritized over the need of multinationals to increase their profits at all costs.

HIV Continues to Enhance Pharmaceutical Companies' Profits

Though it doesn't stop the vigorous campaigning by Gilead to fast-track the approval process for it's Truvada antiretroviral drug for use as pre-exposure prophylaxis, little enough is known about the consequences of a large scale PrEP program. But also, the results of trials so far are far too poor to support widespread use.

The Aids Healthcare Foundation, who are opposed to this fast-tracking, have also highlighte another serious consequence. A serious black market in Truvada has emerged and one US state has passed a law so that the drug can only be prescribed when someone has been diagnosed as having either HIV or hepatitis.

Whatever the consequences of such market manipulation in the US, the same phenomena in developing countries could be very serious. Most people in high HIV prevalence countries receive medication paid for by donors. There is no current funding for PrEP. Therefore, drugs people are not receiving free of charge could rapidly increase in value in a black market.

The ethical problem of supplying a drug that is in short supply to people who are not HIV positive has not been addressed. But the ethical issue of creating a run on a drug that is keeping many people alive, just so some people can try out a HIV prevention strategy that is very unlikely to give them much protection, is also in serious need of consideration.

New HIV infections are not a problem for Gilead, far from it, they are all very welcome news. The development of resistance to cheap drugs is even more welcome as revenue from each 'customer' increases by as much several hundred percent.

Even a few deaths will not put much of a dent in profits, considering the customer base is being increased from a few million HIV positive people to a possible several tens, or even hundreds of millions of HIV negative people added to the current highly lucrative market. The article notes that the drug generated $2.6 billion in revenue in the last year and use of Truvada as PrEP could add anotehr billion to that.

Can HIV Drugs Replace Human Rights?

Here's another interesting post about PrEP from Joseph Sonnabend's blog. In addition to the iPrEx trial showing a very small absolute risk reduction for Truvada, the cost of preventing one HIV infection is also massive. Sonnabend's estimate is about half a million dollars.

Even at a fraction of that cost, it seems unlikely that any high HIV prevalence country could afford PrEP. Nor are any donors likely to be in a hurry to finance a large PrEP program.

But there are a couple of other worries expressed: PrEP will only be appropriate for a small number of people, and they are mostly living in rich countries. And HIV prevention as a whole is in danger of being thrown off course by the euphoria about PrEP. Money which should be going to education could be diverted to drugs which are expensive and of very limited use.

People still need to be aware of the risks of being infected with HIV and of what they can do to avoid it. Spending all prevention funds on PrEP will not have the impact being claimed by the HIV drug industry.

Here in East Africa, there has been so much discussion about people's rights over the years, how those rights have been denied and how this relates to HIV transmission. Are their rights now so worthless that they can be replaced with some overpriced drugs that don't even work very well?

Vital Distinction Between Absolute and Relative Risk Reduction

In order to understand how misleading all the jubilation about recent PrEP trials is, have a look at one of Joseph Sonnabend's two blogs. He explains the difference between relative risk reduction, which is the widely reported finding from the trials, and absolute risk reduction, which is the very low figure that doesn't seem to have been reported at all.

The first blog launches straight into explanations of the two risk figures and an account of why the difference matters so much. But either blog will demonstrate how the whole PrEP issue has been blown up into a 'game changer', in the words of the HIV industry.

Sonnabend shows that the absolute risk reduction is only 2.3%, a far cry from the 44% relative risk reduction reported, which doesn't really give you any way of evaluating the trial results. He also points out that 45 people need to be treated with Truvada to prevent one HIV infection.

There are over 40 million people in Tanzania and only a few hundred thousand of them currently receive antiretroviral drugs, out of well over one million HIV positive people. If PrEP just involved drugs it might be possible to work out the exorbitant amounts of money required, but drugs are only part of it.

It's time for a bit of honesty in reporting figures when it comes to drug trials. There are millions of HIV positive people and tens of millions of people who may be at risk. They deserve the truth.

Why PrEP When Condoms and PEP Would do the Job Better?

I'm still a little puzzled as to why PrEP is considered to be such a great idea, except by the pharmaceutical industry, of course. PrEP is nowhere near effective enough for people to depend on it; they will need to use condoms as well. So why go to such effort and expense? The chances of a condom bursting are very small and if it happens, people can use post-exposure prophylaxis (PEP).

The difference in cost is obvious. PEP would also reduce the likelihood of resistance developing and remove the need for long term adherence. And the side-effects which the pharmaceutical industry don't like to allude to, especially the long term side-effects, will be irrelevant except for the duration of treatment.

[For more about HIV and risk, see my other blog, HIVinKenya]

UNAIDS: Everyone in Africa is at Risk of HIV; so PrEP is Useless?

I've found an uncharacteristically sensible article on PrEP, although it's written from a US perspective. It concludes that "Findings from the randomized clinical trials that PrEP is efficacious should mark the beginning of the policy discussion, not its end."

The article also demands proof of desirability and even deliverability of PrEP before the strategy is implemented. The authors note that sustained and effective counseling is a must to ensure proper adherence to the drugs and that the level of counseling required, which makes up a major part of clinical trials, is unlikely to be part of a community implementation.

Also noted are the lengths that researchers had to go to in order to retain participants in the iPrEx trial, an aspect of such trials that is rarely mentioned when reports of standing ovations at expensive pharmaceutical sponsored conferences come out. The odds during the iPrEx trial seemed to have been stacked against getting a poor result. And yet the result was pretty unimpressive.

The article covers a lot of interesting aspects of PrEP that are rarely mentioned among the post trial hype, such as development of resistance to antiretroviral drugs, increased 'unsafe' sexual behavior among some who think PrEP will give them 100% protection and the sheer cost of such a program that provides drugs for uninfected people when there isn't even enough funding for those who are infected.

But the article, perhaps being written from a rich country perspective, doesn't mention how spectacularly unsuccessful we have been in identifying 'core transmitters' of HIV in developing countries. In fact, any group that could be considered to be contributing significantly to HIV epidemics in high prevalence African countries is dwarfed by the percentage of infections that are said to come from 'low risk' groups.

In short,if PrEP ever proved itself to be feasible in high prevalence African countries, we wouldn't have the faintest idea where to start.

[For more about HIV and risk, see my other blog, HIVinKenya]

Wagging Fingers Hasn't Worked; Let's Try Pills

It is very reassuring that a commentator in Kenya has mentioned, albeit briefly, that providing ARVs to HIV negative people will strain resources in a country where it is not even possible to supply all HIV positve people with them.

Many people don't have food, water, cheap drugs for everyday, but deadly, diseases, contraception and family planning, proper education, infrastructure, and a great many other things. Why the obsession with grossly overpriced drugs that will not make any material differenc to most people's health?

But there are some odd remarks in the article. One person mentioned in the article that she had not had sex with her husband for the first three years after finding out that he was HIV positive. Then she started to use condoms.

So far so good. Condoms give a good level of protection if they are used properly and used all the time. There are all sorts of stories about condoms breaking but this should be rare if people really know how to use them properly. And at least condoms are cheap and have other benefits, protecting against sexually transmitted infections and preventing unplanned pregnancies.

But the article is about using drugs to reduce HIV transmission. This would be in the form of pre-exposure prophylaxis (PrEP), where a HIV negative person takes an antiretroviral drug regularly to reduce the probability of being infected, or 'treatment as prevention', where the HIV positive person takes ARVs which reduce the viral load to a level where HIV is a lot less likely to be transmitted.

If condoms are used, is the risk that the HIV negative partner faces going to be reduced further when they also take PrEP? Perhaps so, perhaps a belt and braces policy gives more protection.

But if the HIV positive partner is on ARVs, taking them correctly, responding to them (to the extent that their viral load is low, etc), does the HIV negative partner need to be taking PrEP? Couldn't the HIV negative partner just make sure that condoms are used?

The more important questions are about whether there will be enough money for all HIV positive people to receive the drugs and other care they need, as well as for HIV negative people to receive the most effective prevention assistance available.

Currently, only 20-40% of people in need of ARVs are receiving them. Will the need for PrEP be given priority over the need for ARVs, given that PrEP is for people who are healthy and normal ARV treatment is for people who are sick and will die without the drugs?

But even 'treatment as prevention' is not that straightforward. The majority of people in most African countries do not know their HIV status. Even the majority of HIV positive people do not know their status. How easy will it be to identify all HIV positive people and keep on identifying new infections for as long as they occur.

Apparently Swaziland is going to test its entire population and put everyone found to be HIV positive on ARVs, effectively, 'treatment as prevention' or 'test and treat'. There are only 1.2 million Swazis but an estimated 200,000 of them are HIV positive.

Yet only about 60,000 HIV positive Swazis are on ARVs and the country doesn't even have enough supplies for them. Similar shortages have occurred in other African countries. Health services can barely cope with keeping a fraction of people on treatment, let alone all those who need them.

The Kenyan article continues with the sort of honesty that you wouldn't normally find in an article about HIV: prevention so far has had little impact and the rate of new infections is still very high; sexual behavior change, the main aim of most prevention programs, has not occurred to any great extent.

But UNAIDS and the HIV orthodoxy have, according to the article, been targeting the wrong people all along. They have been talking about reducing numbers of partners, using condoms and even giving up sex altogether. But many new infections occur in mutually monogamous couples, often among people who take precautions and who don't take risks.

The biggest problem with both PrEP and 'treatment as prevention' is that we have been very poor at identifying where new infections are coming from, so we are still, many years and billions of dollars later, in a poor position to know how to traget these expensive interventions, if the money does miraculously appear.

HIV prevention programs are usually targeted at whole populations, many of whom are not at risk. But even those who are not 'at risk' by UNAIDS' criteria become infected with alarming frequency. The plan seems to be to put as many people as possible, HIV positive and HIV negative, on drugs because, rather than despite the fact that, we haven't a clue why most people are infected.

ARVs appear to have an effect, whether used for PrEP or 'treatment as prevention', but we don't really know who to give them to. So we are going to try and give them to as many people as possible, in the hope that it will work, apparently. Is this modern medicine? It's no wonder people are suspicious about 'public health' programs.

ARV Resistance: the Ultimate Pharmaceutical Industry Wet Dream

Few in the pharmaceutical industry wish to discuss the important issue of resistance developing to antiretroviral drugs (ARV). Resistance inevitably develops but the question is, at what rate? In high prevalence countries, which are also resource poor countries, there are very few types of ARV available. So when resistance develops to the common ones, there are few alternatives left and most of them are prohibitively expensive.

Ed Susman discusses resistance, which seems to develop rapidly in the US. The US has one of the highest average spends on healthcare in the world. People on ARVs there are monitored carefully and their regime is changed relatively quickly when the patient is not responding for any reason. This is unlikely to happen in developing countries, where most detailed monitoring is beyond their reach, for a variety of reasons.

Another thing Susman discusses is transmitted resistance, which means that a person with a resistant strain of HIV can transmit their resistance, along with the virus. Therefore the current rate of resistance could rise sharply, especially where HIV transmission rates are high.

This might be an acute problem in countries where there is talk of rolling out PrEP on a large scale or using HIV treatment as a means of preventing HIV transmission. Huge numbers of people will be on ARVs with very little monitoring and probably fairly lax adherence. Given that it takes many months to discover non-response to drugs and provide a change of regime in some rich countries, this problem is going to be a lot more challenging in poor countries.

Susman does not discuss resistance in a context where some, perhaps a lot, of HIV is transmitted non-sexually. If large numbers of people are being treated in unsterile conditions and HIV happens to be transmitted nosocomially, the rate of resistance to common drugs, usually the only affordable ones, could increase and leave many patients beyond help.

As one of Susman's informants says "individuals infected with HIV who respond to antiretroviral regimens can anticipate a life expectancy that is similar to uninfected people, because of the number of treatment options currently available. However, in these young people who already have lost one or two or more classes of drugs, [there will be] limited options for therapy". The options will be a lot more limited in African countries, if there are any options.

Pharmaceutical Industry Front Group Blows its Own Trumpet

Pharmaceutical industry front group AVAC is blowing the usual trumpet for PrEP because some recent trial results have been encouraging. They said predictably little about results which were not so encouraging.

The problem with PrEP still remains: no high prevalence country has managed to put all HIV positive people on antiretrovirals, not even all those who are at the stage of disease progression where it is a serious threat to their health. Why does anyone think they can roll out a drug for people who are not infected with HIV on the grounds that it might give them 'up to' 73% protection?

If 20% of sexually active people are infected with HIV and most of the other 80% are considered to be at risk of infection, will they all be given PrEP? Think of the cost, the logistics, the high levels of resistance, the side effects, things instititutions like AVAC and UNAIDS don't seem to be willing to discuss sensibly.

It also seems like a humiliating climbdown for UNAIDS and all the others who maintained that HIV is almost always spread through unsafe heterosexual sex in African countries (though hardly ever in non-African countries, however unintuitive that may sound). Are all 'risk reduction' strategies now to cease?

Will we instead just give out drugs and ignore the things we appeared to deplore for the last thirty years, promiscuous men, survival sex, commercial sex work, exploitation, early and unplanned pregnancies, early marriage, concurrent relationships, large numbers of partners, low use of condoms, lack of family planning and whatever other issues we have spent so long bemoaning?

Warren Mitchell from AVAC remembered to thank the trial volunteers, presumably mostly guinea pigs who, if they are African, will never be able to afford the drugs and for whom the money to pay for them may never be raised. I don't suppose he was being ironic, either.

Another move which looks suspiciously like a way to vastly increase the volume of ARV drug sales, and thereby increase dependency on drugs and funding, is a strategy called test and treat (or various other names). This involves testing the whole population of a country regularly, perhaps every year, and putting everyone found positive on treatment.

Testing even a reasonable percentage of people in a population once has remained elusive, let alone the whole population or the whole population every year. But even testing once a year is not thought to be enough, so test and treat is still just a theory. And it is well known that early treatment carries a lot of risks that have not yet been adequately explored.

It is to be wondered if people will be obliged to take the drugs by law or if they will face stigma if they refuse. UNAIDS has many years of experience in the use of stigma as a weapon with which to threaten people and punish them for being African so perhaps they have some plans in this area. No disease has ever been beaten by drugs alone so it seems hard to believe that HIV will be the first. But it is great news for the pharmaceutical industry.

[For more about PrEP and HIV issues in Africa, see my other blog, HIV in Kenya.]

Is the Big Pharma Tail Wagging the Dr Dog?

In addition to the good work that the Aids Healthcare Foundation is doing to question the 'fast-tracking' of the use of Truvada as PrEP when it has so far shown such poor efficacy, a group of 55 US physicians have signed a letter, also urging the US Food and Drug Administration (FDA) to delay approval until further tests, which may take years, have been carried out.

PrEP may be a great theory and Truvada may be a great drug. But there is little to get excited about yet. If effectiveness in the real world (as opposed to efficacy in carefully controlled trial contexts) can reach a reasonable level, which would be a lot higher than the unimpressive 44% found in the iPrEX study, then it will be time to consider the use of Truvada as PrEP.

It's good to hear that some doctors are standing up for their patients. Others appear to be in the thrall, or in the pocket, of Big Pharma. Many AIDS and human rights activists seem to have got the wrong end of the stick on this one: people have a right to safe healthcare, not to be used as free lab-rat material.

Interest in PrEP Wanes with Accurate Information about Effectiveness

The Aids Healthcare Foundation is one of the few very influential institutions questioning the wisdom of rushing into widespread use of PrEP before we really know how well it will work, what challenges it may present and whether it is the best option for some, or even any, risk group.

Their survey is worth a look but a couple of the findings in particular caught my eye. Aside from the fact that most people think they are not at risk, even thought they are sexually active and engaging in anal sex, only 42% say they always use condoms. Saying they 'sometimes' (34%) use condoms is rather vague and may not differ from those who 'rarely' (9%) use them. And 15% say they never use them.

These figures for condom use contrast strongly with answers to the question about using condoms if taking PrEP as well. 83% say they would continue to use condoms if they knew that PrEP was only 90% effective. And only 63% said they would be 'very likely' to remember to take PrEP every day.

The need for regular health visits and other measures only reduce the percentage willing to take PrEP a bit but sharing costs puts a lot of people off. $720 a year results in 59% of people saying they wouldn't choose PrEP. The result is not much different when the cost sharing goes down to $400 per year.

But resistance and side effects are taken very seriously by these health conscious people, many of whom only sometimes use condoms when engaging in anal sex. A small risk of kidney damage or bone loss over a long period of time taking the drugs results in 66% saying they would not take it.

And for the possibility of resistance to certain antiretroviral drugs if the user becomes infected with HIV, which may be far more likely than the side effects mentioned, a whopping 71% say they would not take PrEP. Perhaps they are aware of the implications of resistance, one of which is that the cost of their treatment will rocket.

It's good that the Aids Healthcare Foundation are interested in probing the issue of PrEP, rather than joining in the wholly unwarranted jubilation. Perhaps HIV drug users and potential users are aware that resistance, which is so incredibly valuable to the drug industry, is a potential disaster for them.