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Hepatitis C eradication and profit


Note: This is a guest blog by Helmut Jäger. Dr Jäger’s website and blog provides more information and thoughtful comments on healthcare issues at: http://www.medizinisches-coaching.net/

Good news: hepatitis C can be cured

Since 2016, the World Health Organization recommends treating hepatitis C infection with sofosbuvir (NS5B-Polymerase-inhibitor)The manufacturer (Gilead) demands an extremely high price, and

“.. the public paid twice: for the pharmaceutical research and for the purchase of the product. The enormous profits flow to the Gilead shareholders.”(Roy BMJ 2016, 354: i3718)

The evidence for the effectiveness of direct-acting antivirals (DAA) for chronic hepatitis C comes from short-term trials. Cochrane is unable to determine the effect of long-term treatment with these drugs:

DAAs may reduce the number of people with detectable virus in their blood, but we do not have sufficient evidence from randomised trials that enables us to understand how SVR (sustained virological response: eradication of hepatitis C virus from the blood) affects long-term clinical outcomes. SVR is still an outcome that needs proper validation in randomised clinical trials. (Cochrane 18.09.2017: http://www.cochrane.org/CD012143/LIVER_direct-acting-antivirals-chronic-hepatitis-c.)

Egypt is particularly affected by hepatitis C. Here the government negotiated special discounts with Gilead, so that relatively cheap treatment will be available. It’s the foundation of just another lucrative business based on a man-made disaster.

tourcure

Tour’n Cure: The profitable medical eradication of a problem that would not exist without medicine.

Bad news: Hepatitis C will still be transmitted by skin piercing procedures

About 2-3% of the world’s population is infected with the hepatitis C virus (HCV); 350,000 of these 130-170 million people die per year. HCV causes liver infections, which are chronic in more than 70% of infected persons. That is, they do not completely cure after an infection. After one or maybe two decades, the damaged liver can fail, or develop cancer. The survival rates are low in the late stages of the disease, even under optimal treatment conditions.

Hepatitis C viruses are very sensitive to environmental influences so they are transmitted almost exclusively through blood or blood products or unclean syringes. Unlike hepatitis B or HIV/AIDS, HCV infections through sexual contacts are rare. Hence, the incidence of HCV is an indicator of a dangerous handling of needles, syringes, other medical instruments or products that lead to a direct blood contact. And new cases of HCV are acquired most likely in health care facilities or by intravenous drug use.

Treatment of disease and prevention of new infections 

The World Health Organization (WHO) announced in 2016 that it wants to “combat” hepatitis C and “exterminate” it by 2030. (WHO 2017: http://www.who.int/mediacentre/factsheets/fs164/en/)

unsafe-needles

Hazardous needles somewhere in Africa (image: Jäger, Kinsahsa 1988)

WHO’s optimism is caused by the availability of sofosbuvir. The drug is said to have cured up to 90% of affected patients in clinical trials, and consequently was added to the WHO list of essential medicines. The pharmaceutical company Gilead faces a huge global market with high profit margins (WIPO 2015): The treatment costs in the US are US$84,000 and in the Netherlands €46,000. The production cost of the drug is estimated not to exceed US$140.(‘T Hoen 2016)

Most people affected by hepatitis C are poor. They now learn through the media that their suffering could be cured, and at the same time that this solution seems to be unavailable to them. Consequently, they will demand the necessary funds for humanitarian reasons from their governments. Gilead expects sofosbuvir will not be manufactured and sold without a license (about 100 times cheaper). The Indian authorities already concluded in 2016 a license agreement with Gilead, which will guarantee high profit rates on the subcontinent.(‘T Hoen 2016)

Attractive medical products and markets increase the risk of the production of counterfeit medicines

In India, the requirement to allow the production of the hepatitis C drug in the “national interest” license-free is not only risky for legal reasons. India already is the world’s leading producer of fake medicines. Counterfeit drugs look exactly like real ones, but contain nothing (in the best case) or poison. About 35% of the malaria drugs in the African market are fake or useless, and they are mostly from India or China (see below: fake drugs). In the case of Egypt, medical institutions tried to open up a lucrative international market (“Tour’n cure”). Therefore, it will not be long until the first fake “sofosbuvir preparations” are offered.

The history of the hepatitis C epidemic in Egypt

The disaster of hepatitis C contamination started in Egypt more than sixty years ago. Efforts to regulate the Nile increased the risk of schistosomiasis infections. These parasites cause numerous health problems, mostly in the pelvic organs, and in rare cases, cancer. The worm larvae swim in stagnant water that has been contaminated by human urine or feces, and they enter the blood system of healthy people by piercing the skin.

The frequency of these worm infections increased rapidly after 1964, when the fast-flowing Nile was tamed by the Aswan Dam. In a relatively short time 10% of the Egyptian population was colonized by the parasite. The Ministry of Health then treated large parts of the population with injections containing antimony potassium tartrate. Until 1980 this toxic compound was considered the only effective remedy for this worm-infection. Today it is no longer used, not even in veterinary medicine.

Many years after the start of the campaign an initially unexplained epidemic of hepatitis C  was noticed in Egypt. It turned out that most of the patients with hepatitis C virus received anti-schistosomiasis injections.

Those initially infected with hepatitis C virus had higher risks to be treated in health care facilities, where the virus was then transmitted to other patients. Today (according to different estimates) 3-10% of the Egyptian population is infected with hepatitis C, and 40,000 patients die per year with the disease. Because many patients are infected, today the risk to acquire hepatitis C infection in Egyptian health facilities, even in optimal hygenic conditions, is significantly higher than in countries where hepatitis C is relatively rare.(Strickland 2006, WHO 2014)

Hepatitis C epidemic in industrialized countries

But Egypt is not an isolated case. Hepatitis C affects mostly the residents of developing and emerging countries. But even in Germany more than half a million HCV infections are recorded.

In England, in 2015 the government had to apologize for the infection of nearly 3,000 people who received infected blood products between 1970 and 1990.(Wise 2015)

In the US hepatitis C is called a “hidden epidemic” because 300,000 people were infected each year a few decades ago.(Ward 2013, Warner 2015, CDC 2015, RKI 2015, Pozzetto 2014)

Syringes and blood products are dangerous if handled improperly or if they are used although they are not necessary

blood

Blood Bank in Kinshasa (Congo, 1990, image: Jäger)

Needles (in particular the worldwide introduction of disposable syringes and their inflationary use) contributed to the spread of viruses like HCV, HIV and others.(Jäger 1990-92) The problem of the HCV epidemic is caused by the health care system and its waste products that fall into the wrong hands. The causes of the infections mostly are: bad medicine or intravenous drug addiction. What happened in Egypt is just another example that sometimes (medical) solutions of seemingly controllable health problems can lead to much larger problems: because sometimes “the things bite back.”(Tenner 1997, Dörner 2003)

Therefore WHO’s strategy to eradicate hepatitis C, based only on treatments, cannot succeed as long as the much of the medical sectors in many poor countries remain dangerous-purely-commercial and in large parts uncontrolled. The WHO campaign certainly will enrich Gilead and some health institutions, but a reduction of the hepatitis C incidence will not take place if “bad medicine” and “drug addiction” are not targeted, preferably eradicated, or at least reduced.

Unnecessary medicine is risky and should be avoided

WHO and other international health organizations should strive to avoid unnecessary therapeutic skin piercing procedures, injections, surgery and transfusions, and (if these sometimes life saving procedures are necessary) establish strict quality control. The commerce of medical tourism and beauty-interventions (botox, piercing, tattoo) should be strictly controlled.

unsafe-injection

Hazardous needles anywhere else in Africa (image: Jäger)

And we should invest in training patients: They should be supported to reduce their demand for health-care-products and to increase their knowledge in order to distinguish “good” and “bad” medicine.

 More

Literature

Bad Medicine in economically weak countries (such as “fake drugs”):

Why things bite back

Pre-Exposure Prophylaxis: Risks in the Pipeline?


An estimated 1 million Kenyans are receiving antiretroviral drugs, about 64% of all HIV positive people. Partly as a result of this, death rates, along with the rate of new infections, have continued a decline that started in the early 2000s, and the early to mid 90s, respectively. Now pre-exposure prophylaxis (PrEP) is being added to the country’s HIV strategy, a course of antiretroviral drugs taken by HIV negative people, which should significantly reduce the risk of their being infected.

So this should be a good time to look at how HIV treatment in its various forms should be targeted. ARVs are relatively straightforward, people testing positive can be put on treatment. But PrEP, if it is expected to reduce infections, needs to be prescribed for those most at risk. This is not as simple as it sounds, because HIV resources have so far been flung far and wide in Kenya, as if those who most need them will magically benefit.

The ruling assumption for high prevalence countries has been that 80-90% of all HIV transmission is a result of ‘unsafe’ sexual behavior. HIV prevalence is seen as a reliable indicator of ‘unsafe’ sexual behavior, and ‘unsafe’ sexual behavior, or perceived behavior, is seen as a reliable indicator of prevalence.

This is completely circular, of course. But if these prejudices are carried over from addressing the HIV positive population, and applied equally to the HIV negative population, the bulk of the drugs may as effectively be flushed down the toilet. The majority of Kenyans are, were, or will be sexually active. But the majority are not at risk of being infected with HIV.

Kenya’s HIV epidemic, in common with the epidemics in several other East African countries, is quite old. The virus has been circulating since the 50s and 60s, so the epidemic is about half a century old, give or take a few years. In other countries, such as the DRC, the virus has probably been around for about 100 years, although it must have affected only small numbers of people for many decades.

Don’t be fooled by figures suggesting that HIV has only been around since it was first recognized by doctors in the early 1980s (or just a little bit earlier), and later described by scientists. UNAIDS estimate that prevalence was already about 3% in Kenya by 1990, rising to over 10% later in the decade, to peak at almost 11%. From 2000, prevalence declined for a few years, rose again from 2005, then dropped to 6%.

This suggests that the rate of new infections (incidence) peaked and started to decline in the early to mid 90s, prevalence peaked and started to decline by the late 90s, and death rates would have peaked in the early 2000s. By 2007 prevalence was 8% and it is now 6%, so it has hovered between 6 and 8% for more than 10 years. Declines are slow, irrespective of major interventions.

Although the widespread use of ARVs, which began in the late 2000s, has contributed to a decline in new infections, prevalence and death rates, it is not possible to attribute these improvements to drugs alone. Making PrEP available to all those assumed to be ‘at risk’ of being infected, purely on the basis of the circular argument mentioned above means that this is going to be an expensive, but very ineffective intervention.

This sounds like bad news, but it doesn’t have to be seen that way. If the HIV risks people face could be identified, whether they are sexual or non-sexual, this will reduce the number of people who need PrEP. Most non-sexual risks, for example, exposure to blood and other bodily fluids through unsafe healthcare, cosmetic and traditional practices, are easily and cheaply avoided. No need to give PrEP to all the patients at a clinic when you could just clean up the clinic, right?

But also, things have changed, PrEP allows us to target those most at risk much more accurately than before. If people know they can protect themselves, they will. Clinics can now safely return to the practice of ‘contact tracing’, identifying how each person testing positive may have been infected, and then addressing that source of infection, whether it was a sexual partner, a clinic, a tattoo artist, or whatever.

The decision to discontinue tracing contacts, which was made in a very different context (a rich country, where the bulk of HIV transmissions were occurring among a relatively small population, and resulting from an easily identified set of behaviors) is inappropriate for a country with a massive HIV epidemic, where the risks have not been clearly demonstrated, and averted. In Kenya, for example, the majority of people who become infected with HIV do not face the high risks identified in rich countries, receptive anal sex and injecting drug use.

If identifying how people become infected can allow HIV negative people to avoid being infected, and allow HIV positive people to avoid infecting others, then contact tracing is vital in high prevalence countries. It is also vital if interventions such as PrEP are to be effective, or even affordable. Already, researchers have found that not being able to identify where the risks are coming from will significantly increase the quantity of drugs each person needs, in addition to vastly increasing the number of people deemed to be in need of PrEP.

Despite ample evidence that non-sexual risks are as important as sexual risks, evidence that has been available since the virus was first identified as causing Aids, most research concentrates on reporting sexual risk only, collecting data about sexual risks, recommending strategies to reduce sexual risks only, while ignoring, denying or failing to collect data on non sexual risks.

Mass ARV rollout complements pre-existing trends in HIV epidemics, though not as much as it could have, had the contribution of non-sexual transmission been acknowledged. However, PrEP will be a slow and inefficient solution unless targeted at those truly at risk, as opposed to the tens or hundreds of millions who are sexually active. People can only protect themselves if they know what the risks are, whether they do it by avoiding exposure, or by taking prophylactic drugs.

Drugs for All Deemed More Profitable than Circumcision


Demands to roll out mass male circumcision programs, claimed to reduce HIV transmission, date back at least 20 years. Other claims about the ‘benefits’ of circumcision go back centuries. But by the time the programs had started several other interventions had been identified that have a far better claim to reduce HIV transmission.

For example, ‘test and treat’, the practice of putting everyone who tests positive for HIV on ARVs immediately, is claimed to reduce transmission to a HIV negative sexual partner by 96% or higher. (Note, 90 is something of a magic number in UNAIDSland at the moment, with their 90-90-90 strategy replacing various other magic numbers conjured up in the past.)

PrEP, the practice of giving ARVs to HIV negative people who are thought to be at risk of infection with the virus, is also claimed to reduce transmission to a HIV negative partner by 96%.

If the number of HIV positive people in the world is something around 30 million, depending on which estimates you use, and about half of them are claimed to be on ARVs already, there are still around 15 million who can benefit from ARVs. That’s worth, say, a few billion dollars.

Although a lot of those opposed to mass male circumcision don’t seem to realize this, many of those promoting circumcision are the same people who promoted behavior based programs, particularly those with an emphasis on ‘abstinence’. Those programs, although they never completely died out, were a disaster. Even the people formerly pushing them now admit that they probably had no impact on HIV transmission. But they wanted to find another source of funding to replace the vast amounts that used to go into ‘prevention’, a lot of which was spent on behavior based rubbish.

Circumcision seemed like the answer because the number of people who could be targeted for circumcision could run into hundreds of millions. Every year millions more male children would be available to keep the programs profitable.

At first the promoters claimed they were only targeting sexually active adults, but they quickly found that most of them didn’t want to be circumcised. It was much easier to recruit children and now they can turn their attention to infants.

But with test and treat, coupled with PrEP, how can the circumcision enthusiasts still claim that there is any benefit to the operation? They need to target almost the entire male population in countries where circumcision is not widely practiced. They must carry out the operation on about 75 men for every one claimed reduction in HIV transmission.

The other interventions, test and treat and PrEP, are claimed to be targeted at those most at risk. Let’s take a look at who is thought to be most at risk, and see just how many hundreds of millions of people that involves, who would need to be taking these drugs for the rest of their lives in the case of test and treat, and for as long as they are thought to be at risk for PrEP.

In western countries there are few groups who are thought to be at risk. The biggest group is men who have sex with men. The second biggest group is injecting drug users. But aside from commercial sex workers, who are given some choice in prevention options in many rich countries, there are not many others.

The picture is completely different in southern and eastern African countries, with high prevalence and/or large numbers of people infected with HIV. This article about a PrEP program in Kenya says the groups of people claimed to face the highest risk of being infected include:

  1. Discordant couples (where one partner is HIV positive and one is HIV negative)
  2. People who frequently contract sexually transmitted infections
  3. People who are said to be unable to ‘negotiate’ condom use
  4. People who frequently use post-exposure prophylaxis (a short course of ARVs for people who suspect they may have been infected, taken within 72 hours of contact)
  5. People who share injecting equipment

Out of the estimated 77,600 new infections in Kenya it is not clear how many arose among any of the listed ‘risk’ groups. High prevalence countries tend not to trace contacts, assuming that the bulk of transmissions (about 90% if you exclude infants said to have been infected by their mothers) were a result of heterosexual intercourse.

You could easily add other risks to the above list, for example (most of the following are a risk in developing countries although 7, 10 and 12 are likely to be more common in rich countries):

  1. People who have given birth in a health center/clinic
  2. People who have given birth at home, or anywhere other than in a health center/clinic
  3. People who have received birth control injections
  4. People who have had injections, blood tests, transfusions, dental care, infusions, etc
  5. People who have had operations that involved piercing the skin, major or minor (including circumcision)
  6. People who have received some forms of traditional healthcare that involved skin piercing
  7. People who use injected appearance or performance enhancers (eg botox, steroids, etc)
  8. People who get their head shaved or where skin is pierced and/or weakened by processes
  9. People who receive manicures, pedicures, etc
  10. People who have body piercings
  11. People who practice scarification and other practices
  12. People who get tattoos

Of course, with the second list, you could warn people about the risks and clean up health centers, cosmetic establishments and anywhere skin piercing occurs (the list is surprisingly long). This would seem preferable to putting almost everyone in a population on expensive drugs for many years.

But UNAIDS, CDC, WHO and other establishments object to calls to warn people about the risks they face in health and cosmetic facilities in developing countries. They warn some people from rich countries about the risks in poor countries but they refuse to warn people in poor countries.

Even concentrating on the risks listed in the Kenya article it is easy to identify many millions of people who could be said to need the $775 per annum PrEP, which is the estimated cost of the drugs alone (I don’t know what other costs there may be).

So you can see the attraction for the HIV industry. If there were only 5 million people requiring years of ARVs, for some, a lifetime of ARVs, that’s several billion dollars for Kenya alone. There are countries with higher prevalence and others with higher numbers of people infected than Kenya.

With only a few billion dollars for mass male circumcision, with its 1.3% absolute risk reduction, or even the claimed 60% relative risk reduction, drugs for the sick and the well seems like a far more lucrative strategy. Even if the benefits realized for mass male circumcision far exceed those unlikely claims, they can’t come close to the claimed benefits of test and treat and those of PrEP.

One problem is that you can’t roll out PrEP for many of the groups claimed to benefit. For example, in discordant couples the positive partner should already be receiving ARVs. People who share injecting equipment could be better served by a clean syringe and needle program. There may be other examples, where overlapping PrEP and test and treat might raise eyebrows among the more scrupulous in the industry.

And it would be perverse to give PrEP to people while they still attend clinics and other places where skin piercing procedures take place without warning them about the risks and also ensuring that those places start to abide by strict infection control regulations that people in rich countries (and rich people in poor countries) enjoy.

If PrEP and test and treat strategies are as wonderful as we are told, let’s hope they do as well in the field as they did in trials. But let’s also get rid of these silly mass male circumcision programs. We no longer have to pretend that they will reduce HIV transmission, or even pretend that that’s why they were rolled out in the first place. Worse still, the profits are orders of magnitude lower than the drug based strategies.