HIV Drugs: Expert Opinion Trumps Randomized Controlled Trial

One of the biggest HIV industry funded junkets on the calendar, the International Aids/Antiviral Society's (IAS) AIDS 2012 Conference, is currently underway in Washington DC, the area with the highest HIV prevalence in the Western world. Conspicuously, despite an avowed commitment to fighting stigma, many of the most prominent victims of HIV related stigma will not be attending the conference as sex workers and other stigmatized groups are unable to get a visa to visit 'the most democratic nation on earth'. They have been relegated to a small and less well funded conference in India.

The IAS is said to be the "world's leading independent association of HIV professionals". But my attention has been drawn to their new guidelines on 'treatment as prevention', hailed as a 'game changer' in the press. This is the use of antiretroviral drugs as soon as the patient has tested positive for HIV, as opposed to waiting until they have reached a particular clinical stage, which is what happens at the moment.

The authors of the guidelines disclose conflicts of interest that read like a who's who (or should it be 'whose') of Big Pharma. In addition, it appears that treatment as prevention is being adopted as a strategy before the results of a randomized controlled trial have been reported, a trial designed to answer questions such as when is the best time to start taking antiretroviral drugs.

As well as casting doubt on their independence, the use of expert opinion to trump evidence based medicine also raises a serious question about their professionalism; if the results of the trial are preempted by these experts' recommendations, what is the point of the trial? What if the trial results, due some time in 2016, contradict their conclusions? The possible risks of early antiretroviral treatment include various short and long term side effects, the development of resistance to these and similar drugs and, presumably, other possible risks that can not be listed until the trial has finished.

One of the objections raised to treatment as prevention is that many people who are already in urgent need of ARVs, especially in high prevalence countries, are unable to get the drugs. So would it be acceptable to start doling out these extremely expensive drugs to the potential millions of people who may be HIV positive, but are not currently judged to be in need by their physicians?

Much of the demand for early treatment, treatment as prevention and pre-exposure prophylaxis arises in wealthy countries, where HIV prevalence is relatively low. This demand is actively encouraged by the pharmaceutical companies who produce the drugs; so it's a match made in heaven for some. Even if resistance does develop, many people in wealthier countries can still afford (or their insurance company can still afford) the much more expensive second round drugs that must be used. But if first round drugs are unavailable to many in developing countries, second round drugs will be unavailable to almost everyone there.

Despite hearty reassurances that adherence to complex drug regimes was not a problem in poor countries in the early days of mass treatment, research has shown otherwise (perhaps demonstrating the difference between expert opinion and evidence based medicine). The BBC cites research that the most rapid increase in ARV resistance occurred in East Africa, where HIV prevalence is medium rather than high. Resistance was found to have occurred at 29% a year there and at 14% in Southern Africa, where prevalence is high.

The BBC article goes on to say that adherence can be improved by measures such as access to food and clean water. This is a reminder that many Africans receiving 'treatment' for HIV get little more than a bottle of pills and a bit of finger wagging. They may swallow the pills with contaminated water and eat little food to help them tolerate medication which can be toxic to people who are suffering from poor nutrition. Numbers on treatment seems to be a lot more important than the precise impact the mass treatment strategy is having on the epidemic.

The real 'game changer' in the HIV industry would be to put HIV in perspective; it is one disease out of many health issues and it is no more independent of people's overall health than any other disease. Could there be a more poignant signal of how out of perspective HIV is than the realization that many infections over the last 20 years could have been averted if more attention had been paid to prevention through improving health and other social conditions? And even HIV positive people often die of easily preventable and treatable diseases, such as water borne diseases, respiratory infections and the like.

Treatment as prevention is depicted as an effort to treat every HIV positive person in order to decrease onward transmission of HIV, but it is, in reality, a strategy to sell overpriced drugs to as many people as possible. It goes hand in hand with early treatment and pre-exposure prophylaxis, which all together should increase the market for ARVs from less than 10 million people to many tens of millions of people. And spending ever increasing billions on this one disease means that less is spent on the sort of things that really improve the lives of people in the poorest countries, such as health, education, infrastructure, employment and social services.

It is worth reflecting on the 'risks' that those taking part in the randomized controlled trial of early ARV treatment face: side effects are an opportunity to try different drugs and different combinations of drugs, even more expensive drugs. The risk is to those receiving the drugs, not to the pharmaceutical company. And resistance, of course, represents an even more significant opportunity because the response is far more expensive drugs. People, once on these drugs, will need to take them for life. What could be better for Big Pharma? So why wait for an irritatingly long trial when you can just pay experts to tell the world what you would like them to hear?

[For more about non-sexual HIV transmission and mass male circumcision, see the Don't Get Stuck With HIV site.]

English Guardian Issues Press Release On Behalf of HIV Industry

It's not rocket science and there's probably even a name for it, I just don't know what it is. But when a company wants to charge a ridiculous price for their product, they have to start with something astronomical. Suppose the ridiculous price was $100, the seller needs to put the word around that they will be charging $1000. Everyone will gasp, but they will praise the seller when the price is very publicly dropped to $800 and, over a period of years, goes down to $200, double the price the seller originally wanted.

Of course, sales of antiretrovirals are now very much higher than they were years ago, when the cost of the drugs was in the thousands of dollars per year. Numbers of people on treatment was in the tens and hundreds of thousands at first. But once the market expanded to millions of people the drug companies could afford to drop their prices by what looked like substantial amounts. Bills Gates and Clinton and anyone else jumping on the bandwaggon could happily boast about how 'cheap' treatment was, as long as no one looked beyond the drug costs. Generic versions of the drugs could be made for a fraction of the cost but this was exactly what the philanthropic foundations did not want, non-patented drugs undercutting Big Pharma.

Now Bill Clinton's organization, which specializes in lobbying for higher quantities of (patented) antiretroviral drugs to be sold to developing countries and paid for by 'aid' money, is claiming that the entire costs of treatment, not just the drugs, is much lower than anyone realized before. The 'game-changing' work by Clinton's Foundation just happens to be ready for the forthcoming International Aids Conference in Washington, which is a very expensive forum for the HIV industry to move its latest products and strategies up the agenda (and will doubtless host a number of 'game-changers' over the course of the event).

In the five countries the Foundation researched, the entire costs for treatment came to an average of $200, which says a lot about how badly health professionals are paid and what exactly 'treatment' includes in developing countries. But the argument was never really about cost alone. The argument was about how much money certain multinationals could make and how quickly they could make it. Instead of advocating for the development of health systems, building new hospitals, training more health professionals, increasing the amount of money spent on health and other social programs and the like, the HIV industry agenda has always been about cherry-picking the most profitable strategies.

Thirty years into the pandemic an estimated 2.5 million people will be newly infected with HIV in the next 12 months and nearly two million will die. And yet the big conferences are all about commerce and politics. But why are so many people still being infected with HIV every year and why are so many still dying? The industry, for political reasons, can just point to sexual behavior. But why do we still not know what kind of sexual behavior could give rise to such high transmission rates or how such high levels of 'unsafe' sexual behavior could occur, or if they even do occur?

In Western countries, HIV transmission has been primarily a problem among men who have sex with men and people who inject drugs. But rates of male to male sex are no higher in high HIV prevalence countries in Africa than they are in the West and intravenous drug use is generally a lot lower. And the vast majority of people infected are neither men who have sex with men nor intravenous drug users. In fact, the majority are people who face very low sexual risks and there are far more heterosexual women than men infected. 'Women are more susceptible' says one of the mantras of the HIV industry; but they are not more susceptible in Western countries. In the West, few women are infected through heterosexual sex and almost no men are.

Clinton's Foundation, naturally, latches on to the 'treatment is prevention' reflex that the HIV industry currently pins its hopes on. After all, this could eventually take numbers on treatment from mere millions to tens of millions. Almost anyone who is HIV positive could be 'put on treatment' (and in developing countries, the idea of choice does seem to be absent), as if they are a risk to the public unless they are 'adhering' to a drug regime that is claimed to prolong their lives and ensure the health of those around them. (The SERO Project puts forward a similar line of reasoning about treatment as prevention, but entirely from the point of view of the US and similar contexts.)

The 'sexual behavior of Africans' is to blame, according to the HIV industry, ably fronted by an entire UN institution, UNAIDS. Article after article attests to the entire lack of sexual continence throughout the whole of sub-Saharan Africa. The more restrained factions tend to blame feckless men and bemoan the lot of their female 'victims', who tend to outnumber the men when it comes to being infected with HIV. But the fact that levels of sexual behavior do not generally correlate with HIV transmission rates, despite this being well established, is rarely alluded to by a hungry industry.

The HIV industry continues to claim that 80 to 90% of HIV transmission is through heterosexual sex in African countries, even though heterosexual transmission is the exception in Western countries. The industry also claims that almost no transmission occurs through unsafe health care practices, such as reuse of single use needles, improper use of gloves and various other lapses in infection control procedures. Not only are HIV and other diseases transmitted through unsafe healthcare, but such isolated outbreaks can result in hundreds and even thousand infections in a short space of time, something even eye-watering levels of 'unsafe' sexual behavior could not do.

But while nosocomial outbreaks of HIV and other diseases are regularly and publicly investigated in Western countries, this has never happened in sub-Saharan Africa. I mean that investigations have never been carried out, not that such outbreaks have never occurred. They may never occur, but looking at the low figures for treatment that Clinton's Foundation cites, it sounds like health services get by on a shoestring. And if HIV, one of the most hyped viruses in history, gets by on a shoestring, it's hard to imagine how badly funded less media (and industry) friendly health issues get by.

The Guardian article cited above is a dolled-up press release for the Clinton Foundation and the pharmaceutical and HIV industry it represents (and the Gates Foundation, which funds the Guardian's Development section). It is not a 'breakthrough' or a 'game changer', which terms readers should recognize as clear signals that what they are reading is hype, and not genuine research findings. HIV treatment is treatment; it's what HIV positive people need when they have reached an appropriate clinical stage; it is not prevention. HIV prevention will only be achieved when serious outbreaks, which are very common in some African countries, have been investigated without prejudice, commercial interest or anything else skewing the findings.

[Note: the "average of $880" the Clinton Foundation estimates for treatment seems high compared to the "between $450 and $800" in another study, published in a peer reviewed journal. This could take quite a lot of the wind out of the Clinton sails, especially considering that publicity is just wind. I wonder how much scrutiny some of the other Clinton Foundation claims could bear.]

Prejudice Can Determine Which Hypotheses Are Tested

The 'no sex for a month' idea was big news for the usual period that these fads can hold the media's attention. But now that it has been 'tested' by a mathematical model and found to be no better than other HIV prevention strategies, the press is not quite so interested. However, measuring its possible effectiveness against other strategies and finding it to be no better is sneaky because it doesn't emphasize quite how ineffective the other strategies really are, nor why they are all ineffective. As the authors say "Despite significant investment in programmes for the treatment and prevention of human immunodeficiency virus (HIV) infection, the prevalence of such infection in sub-Saharan Africa remains stubbornly high."

Before anyone rushes to point out that prevalence figures in some countries remain higher because widespread treatment keeps more HIV positive people alive, they should also bear in mind that "for every two individuals starting treatment, five become infected with HIV": incidence is also still high. Which is even worse for the 'treatment is prevention' brigade, because it isn't, especially in high prevalence countries. The percentage of HIV positive people on treatment may not be high enough to test the 'treatment is prevention' hypothesis, but the strategy is clearly not enough on its own.

Parkhurst and Whiteside are good at milking the publicity machine and are aware of the benefits of toeing the HIV industry party line. As well as attracting press attention, a 'no sex month' assumes that most HIV transmission is a result of heterosexual sex. Some probably is, perhaps most is, but we don't know the relative contribution of sexual an non-sexual transmission. Where non-sexual transmission, such as through unsafe healthcare or cosmetic practices, is common, a no-sex month will have very little impact. Worse, it will deflect attention from practices that risk transmitting all sorts of blood-borne pathogens, such as hepatitis, bacterial infections, scabies and whatever else.

Sadly, Kenya is said to be considering such a campaign; they wouldn't want to miss the opportunity to get more funding for yet another useless strategy, and there's also the publicity. Worse still, Swaziland, with one of the worst HIV epidemics in the world, is also said to be considering a no sex month campaign. So I hope they read the article that shows that the strategy is like all the others: media-friendly hype.

People who give up something (or try to) for Ramadan, Lent or any other period will know how hard it is to break a habit or deny themselves a pleasure, even for just a month. But where an addiction or compulsion is involved, even reducing ones indulgence is difficult, and may not happen at all. Alcoholics and people with certain eating disorders, for example, may be able to release themselves completely from something that blights their lives if it were possible for them to stop for just one month. But sex, for most people, is neither a habit, an addition nor a compulsion. It's an appetite, a normal, healthy appetite at that. It's also a human right.

Many people can and do exercise self control as and when they need to. But what is the status of an imperative such as a 'no sex for a month'? It's irrelevant for most people, even in relatively high HIV prevalence countries; most people are not HIV positive, many who are are not sexually active, many don't have HIV positive sexual partners. A blanket, self-imposed ban on sex for a month is nothing like a similar ban on smoking, drinking, overeating, sugar consumption, drunk driving, texting while driving or anything else that results in high levels of injury or bad health. And banning any of those addictions, compulsions and anti-social habits has rarely had much impact. A no sex month wouldn't even have the arguable advantage of a religious motivation.

The mathematical modelling exercise is useful because it finds that none of the interventions show much benefit; it's not just the no sex month idea that is unlikely to give benefit, even if everyone were to magically abstain from sex for a month. But there are also interesting thought experiments around a no sex month. During Lent, chocolate eating, alcohol consumption, smoking and whatever else is probably more concentrated in high-user groups, those most likely to benefit from abstaining from their addiction, habit or compulsion. Heterosexual HIV transmission should end up being confined to those most likely to transmit heterosexually in the normal course of events!

If a no sex month didn't look like a non-starter before you thought about it for a few minutes, you would quickly dismiss it after a few minutes. It just shows you how much time, resources and effort could be avoided with the employment of a bit of thought. But where money and careers, even egos are involved, there's no accounting for the conclusions people will arrive at. The authors "do not conclude that an intervention based on a yearly no-sex or safe-sex month would be ineffective, merely that it would be as effective as an alternative policy that spreads out the reduction in transmission across the whole year".

However, money, careers and egos probably are involved and the silly idea, the sort that the media like the most, may result in more wastage and increased morbidity and mortality, or at least a continued failure to reduce these. The authors recommend comparing a no sex month strategy with male circumcision, concurrency reduction messages and condom promotion. But these, while possibly not so silly, have been shown to be wrong headed and/or ineffective. Different things need to be considered, not more of the same. As a non-scientist, I would suggest that a reduction in anti-African and anti-female prejudice among HIV researchers and the HIV industry could do more than the combined benefits of all the clever and stupid ideas that have been discussed over the last 30 years.

[For more about non-sexual HIV transmission and mass male circumcision, see the Don't Get Stuck With HIV site.]

Uganda's HIV Response: Hit Snooze Again

There have been several mentions of results from Uganda's 2011 Aids Indicator Survey over the past 6 or more months. However I can't find a copy of the report anywhere, not even the highlights or executive summary. But the news doesn't sound good. According to one of the newspaper mentions, the number of people infected with HIV has increased from 1.2m in 2005 to 2.4m today. That's a heck of an increase for a country that is supposed to have been the first in Africa to bring the epidemic under control.

As usual, someone has pointed out that high prevalence does not necessarily mean failed prevention policies because if more people are on treatment they will live longer, keeping the prevalence higher. However, the figure is increasing quickly, not staying the same. Tens of thousands of HIV positive people still die every year. The fact that about half of the 600,000 people eligible for treatment are receiving ARV drugs is great, but it's probably better not to draw too much attention to an epidemic that more than doubles (almost half a million probably died) in 7 years, despite the amount of money being spent on treatment.

The 'treatment as prevention' strategy, which goes under various names, involves the hypothesis that if every HIV positive person, or at least 80% of them, were to be put on ARVs straight away, they would be far less likely to transmit HIV to others. Transmission among people responding to treatment has been shown to be very low. But Uganda struggles to keep less than 15% of HIV positive people supplied with drugs, with frequent stock outs and many people being lost to follow up every year and resistance developing at an increasing rate.

There is still the constant argument and counter-argument about promiscuity and the rest, but this aspect of HIV transmission is now sounding rather idiotic. It's been going on since the 1980s. If people want to believe that a few sound bites about abstinence and faithfulness had any significant influence on the course of the epidemic, let them. But it's not having any influence any more, nor has it likely to have played any part for the last 20 years. It's time to move on.

Another article claims that HIV prevalence in Kabarole district among secondary schools is 30%. If that's true, and I have no way of corroborating it, such an outbreak would need to be investigated. It is claimed that a lot more females than males are infected, which is attributed to cross-generational sex. Males, on the other hand, are said to have been infected since birth.

The proportion of males infected must be very small indeed as prevalence among children under 5 is less than 1% and many of them will not survive into their teenage years, let alone adulthood. The percentage of children receiving treatment for HIV is also very low. Someone interviewed for the article said they want to avoid infections by using the ABC (abstain, be faithful, use a condom) strategy, presumably believing that it was used successfully in the past.

Perhaps believing it will be successful in the future, despite evidence being slight, students in a Uganda high school are putting their faith in male circumcision. The target of 1000 students was exceeded by 23, so now those extolling the virtues of circumcision have to ensure that neither the students nor their sexual partners believe that they can enjoy unprotected sex just because the male has had the operation. You'd think that wouldn't be too hard, but research has shown these beliefs to be common.

Sadly, although male circumcision may reduce HIV transmission from females to males, prevalence is currently a lot higher in females; and male circumcision may increase transmission from males to females. So it's hard to see any net benefit.

Instead of obsessing about sexual behavior, which is probably not that different in Uganda than in many other countries, those who express concern about HIV transmission rates could take a look at conditions in health facilities. If they expect people to use those facilities, safety and infection control procedures would need to be increased. But hospitals and clinics are understaffed, underfunded, there are shortages of drugs, equipment and supplies, standards of safety and hygiene are appalling. This is likely to have some influence on HIV transmission rates. But even if it doesn't, everyone will benefit from better health and healthcare and confidence in health service provision will increase.

But somehow, I can't see campaigns to improve health services, nutrition and food security, water and sanitation, infrastructure and education having quite the headline grabbing value as campaigns about sex, Africans, HIV positive babies, abstinence, condoms and whatever else the publicity people at UNAIDS dream up. I imagine the 'Woes of Tororo Hospital' and 'Kitgum Hospital - a Facility Falling Apart' receive a lot less attention than ones about circumcision, sex in schools, gay bashing and HIV figures doubling. It's hard to know what proportion of HIV is transmitted through non-sexual routes, such as unsafe healthcare. But it's unlikely to become clearer until healthcare associated HIV infections are properly investigated.

[For more about non-sexual HIV transmission and mass male circumcision, see the Don't Get Stuck With HIV site.]