Alarming surge in drug-resistant HIV uncovered
nature.com
nature.com
PrEP should be really cheap (~£10/mo) but the generic status of Truvada (emtricitabine and tenofovir) is being held up by legal shenanigans, so the NHS tariff price is currently £355.73/mo for the branded formulation. This has obviously severely constrained availability on the NHS, so a lot of at-risk individuals are just buying the generic online.
> It has been estimated that the average lifetime cost to the NHS for a person living with HIV is £360,000. Around two thirds (68%) of these costs were for anti-HIV drugs. The cost of a year’s HIV treatment is about £11,000 and of PrEP £5,000. The NHS obtains Truvada at a cost of £3,000–£4000 per person per year. People need to take HIV treatment for the rest of their lives but PrEP will generally be needed for a much shorter period. It is believed that the patent for one of the key drugs in Truvada, Tenofovir, expires in 2017, slashing the cost of the drug from this time. There has been a collective call on Gilead, from those involved in PrEP activism, to lower the price of Truvada for use in PrEP, as there are concerns that PrEP may not be deemed to be affordable.
$6000 for a 'one off' course of treatment sounds very expensive.
The NHS does not prescribe PEP long-term for anyone.
For HIV+ people, it prescribes HAART, which everyone who has HIV should be on.
HIV- people can take PrEP, which is different from PEP and does not include any NNRTIs.
Just shameful.
For those curious; in Australia, it's prescribed and costs about $50-60 p/month. In the UK, it varies; England and Wales are doing trails, and Scotland it's prescribed. Under the NHS, it's £9. In Canada, the generics cost upward of $300 per month.
You might think it's improper, but the evidence says otherwise - PrEP is safe, well-tolerated, marginally cost-effective at proprietary prices and clearly cost-effective at generic prices.
One of the fundamental principles of modern medicine is informed consent. Patients have the right to make their own decisions about their treatment based on their own assessment of the risks and benefits. PrEP is an incredibly compelling proposition for a lot of patients.
PrEP is well tolerated given it's known side effects but conservative medicine dictates that we don't prescribe medications unless we have a measurable benefit and that's not a large group of people. A homosexual male who has lots of unprotected sex with strangers should probably be on it. A hetereosexual mostly monogamous person probably shouldn't be.
A big factor here is that the prevalence of HIV in the US is low, at .34%. Globally it's a bit higher at .48%. It is also often not that contagious. That being said, under the right circumstances it could be so it's real important to be aware of the risk factors.
My husband and me both take prep, his first Doctor refused since it promoted "promiscuity" and would only prescribe it if you are in a relationship with someone positive.
Which is bull.
Find a new doctor that is actually sex positive and won't refuse it for stupid reasons.
(Admittedly I am lucky where I am though to have a doctors office that focuses on LGBT issues, which happens to include HIV prevention/care)
On January 25, 2007, Thailand’s interim government issued compulsory licenses–which require
manufacturers to license generic versions of their patented drugs–for two Western medicines:
Kaletra, an advanced anti-AIDS medicine manufactured by Abbott; and Plavix, a blood-thinning
treatment to help prevent heart disease, produced by the France-based Sanofi-Aventis and U.S.
firm Bristol-Myers Squibb. These attacks were preceded in November 2006 by a violation of
Merck’s patent on the anti-AIDS drug Stocrin.[5] The government threatened to break
patents on eleven more drugs.[6] Explaining the rationale behind Thailand’s decision, health
minister Mongkol Na Songkhla said that “the move is permissible under international trade
rules in the event of national public health emergencies. . . . We have to do this because we
don’t have enough money to buy safe and necessary drugs for the people under the government’s
universal health scheme.”[7]
Perhaps "evergreening" is also an issue in the USA that might keep prices high for a long time?
> On January 25, 2007, Thailand’s interim government issued compulsory licenses–which require manufacturers to license generic versions of their patented drugs–for two Western medicines: Kaletra, an advanced anti-AIDS medicine manufactured by Abbott; and Plavix, a blood-thinning treatment to help prevent heart disease, produced by the France-based Sanofi-Aventis and U.S. firm Bristol-Myers Squibb. These attacks were preceded in November 2006 by a violation of Merck’s patent on the anti-AIDS drug Stocrin.[5] The government threatened to break patents on eleven more drugs.[6] Explaining the rationale behind Thailand’s decision, health minister Mongkol Na Songkhla said that “the move is permissible under international trade rules in the event of national public health emergencies. . . . We have to do this because we don’t have enough money to buy safe and necessary drugs for the people under the government’s universal health scheme.”
Fucked up private insurance in US, they charge that much and then do the reimbursement so they can bill the huge monthly cost to plans / government that will cover it.
We should be giving this out for free.
My MD said Truvada might go generic next year, so perhaps there's hope.
The US should establish an agreement whereby US patients pay a LOT less but that the foreign patients need to pay the same.
The amount the industry earns should be low enough to make it reasonably financially accessible to patients but high enough to prompt our best and our brightest to pursue new drug development as a career.
> Adjusted product gross margin was 87.3% compared with 84.2% in the year-ago period. Research & development (R&D) expenses were relatively flat at $916 million. Selling, general and administrative (SG&A) expenses increased 20.8% to $1.01 billion.
https://finance.yahoo.com/news/gilead-gild-q2-earnings-sales...
They’re doing OK, I think.
What about when you take all the pharma companies and average how well they do over several years? The average net profit margin for the industry is 14.05% according to a January 2018 study by New York University’s Stern School of Business.
14.05%, not great, not terrible.
In addition, the overwhelming majority of those dividends and share buybacks from one company are subsequently plowed back into the industry in different companies depending on which of those companies are working on the most profitable drugs.
source: I have several friends that control a lot of AUM that specialize in pharma investments.
Well, the discussion was about the atrocious cost of HIV medication, and Gilead is the company that holds the patent on Truvada. You didn't provide a link, but http://pages.stern.nyu.edu/~adamodar/New_Home_Page/datafile/... suggests it's actually lower in 2019 at 10.94%.
From the linked Excel sheet there, there are 28 industries with higher net margins, and 65 with lower net margins. They're still doing just fine :).
As I said, not great, not terrible. They're doing just fine, but they are also far from abusing their position. An industry abusing its position would be one with higher net margins than almost all other industries. The fact that 30% of industries have better net margins suggests that this industry is far from being abusive in its pursuit of profit while improving people's quality of life.
Profiting off someone's misery would be when you cause the problem and provide the solution. If you merely recognize an existing problem and provide a solution where there previously was none or where the previous solution was inadequate/inferior.
Attitudes like yours makes me not want to continue using my talent to create on solutions to problems that qualitatively and quantitatively improve people's lives. If people are going to look at it as profiting off misery and deny me the opportunity to increase my wealth, I and others will just take our talents elsewhere. There is no lack of other industries and problems where those capable of contributing solutions can make money and not be subject to your shitty attitude towards how they make a living.
Lastly, I say all this as someone who takes an orphan drug myself that would not exist at all if the US didn't have a legal framework that gives pharmaceutical companies the incentive to bring drugs to market. The drug I take is available in only one other country and only because a US pharmaceutical company brought it to market.
The consumer didn't choose to have greedy companies that like to make a quick bug over someones suffering.
This is pretty simple semantics. Not sure what you're struggling to understand here.
All they talked about during the dinner was price fixing, tricky deals to block generics, and schemes to maximise the amount they could get each country to pay. Nothing about the science, medicine behind the drugs, or benefits to patients.
That's the reality of pharma today.
That people are flying abroad is the start of ripping up their local monopoly along with uncertifified online pharmacy importation and grey market sales - taking risks to avoid costs is a sign that the market /isn't/ bearing it.
https://www.investopedia.com/articles/personal-finance/08061...
There would be costs involved but they can always tell them to get stuffed and manufacture their own if they won't be reasonable. Notably there is a lack of pharmaceutical companies who decide to abandon world markets entirely because positive N is always greater than 0.
https://media.xconomy.com/wordpress/wp-content/images/2014/0...
I am not sure this explains the discrepancy between the healthcare cost between US and Switzerland.
More in depth analysis:
"There were two causes of this massive increase: government policy and lifestyle changes.
First, the United States relies on company-sponsored private health insurance. The government created programs like Medicare and Medicaid to help those without insurance. These programs spurred demand for health care services. That gave providers the ability to raise prices. A Princeton University study found that Americans use the same amount of health care as residents of other nations. They just pay more for them. For example, U.S. hospital prices are 60 percent higher than those in Europe. Government efforts to reform health care and cut costs raised them instead. Second, chronic illnesses, such as diabetes and heart disease, have increased. They are responsible for 85 percent of health care costs. Almost half of all Americans have at least one of them. They are expensive and difficult to treat. As a result, the sickest 5 percent of the population consume 50 percent of total health care costs. The healthiest 50 percent only consume 3 percent of the nation's health care costs. Most of these patients are Medicare patients. The U.S. medical profession does a heroic job of saving lives. But it comes at a cost. Medicare spending for patients in the last year of life is six times greater than the average. Care for these patients costs one-fourth of the Medicare budget. In their last six months of life, these patients go to the doctor's office 29 times on average. In their last month of life, half go to the emergency room. One-third wind up in the intensive care unit. One fifth undergo surgery. "
https://www.thebalance.com/causes-of-rising-healthcare-costs...
You can read the rest it is very informative. I still don't think that healthcare cost in the US is caused by the rest of the world not paying their fair share in drug discovery.
That's a rather weird statement.. I suppose it's true in some sense, but what I'm reading online from real people in the US is that they get bills that are easily 10-100x as much money for going to the hospital than I get.
There's a few others I wonder about:
> These programs spurred demand for health care services. That gave providers the ability to raise prices.
At least requires some numbers, because I'm constantly hearing about Americans not going to the doctor because for the real fear it might bankrupt them.
> The healthiest 50 percent only consume 3 percent of the nation's health care costs.
This is also questionable. Again maybe technically true, but not suitable for conclusions.
The ailments, pain and other bad stuff that Americans will walk around with instead of going to the doctor is incredible (again for the real fear it might bankrupt them). In the US I spoke to a real person who was trying DIY dentistry. There was an AskReddit thread about what general advice doctors say people shouldn't do, and the top advice was: don't perform operations on yourself.
I'm pretty sure it's the price driving down demand.
> The U.S. medical profession does a heroic job of saving lives.
Wait, why does it suddenly stop comparing to the EU?
> But it comes at a cost. Medicare spending for patients in the last year of life is six times greater than the average. Care for these patients costs one-fourth of the Medicare budget. In their last six months of life, these patients go to the doctor's office 29 times on average. In their last month of life, half go to the emergency room. One-third wind up in the intensive care unit. One fifth undergo surgery.
And this is different in the EU because ... ?
I don't like these statistics. I think they're using them to lie with.
I was reflecting to this. If drug cost is part of healthcare cost than by definition it cannot be apples to oranges comparison.
Also about 20% of Americans are on medicaid, and generally do not pay any premiums, deductibles, or copays
It costs about £30 pm in that case which is about $40
Often they'll be running studies at the same time to assess the feasibility of Prep on the NHS.
https://www.who.int/tb/areas-of-work/drug-resistant-tb/xdr-t...
What if it becomes common enough to get into the water at much lower doses? What if people split pills to reduce costs? ISTM that there are many potential avenues for evolving resistance.
If someone is using PrEP and is exposed to HIV, then either the drug works and they avoid infection (in which case there is obviously no impact on drug resistance) or they become HIV+. But in that case, they were either exposed to an already-resistant variant, or they were astonishingly unlucky and the drug failed to prevent infection - in which case, resistance is a moot point.
A person needs to develop an active HIV infection in order to communicate the disease to another. PrEP prevents this from happening in the first place.
That's why it's important for people taking PrEP to be screened regularly, and put on a proper cocktail if they test positive.
https://en.wikipedia.org/wiki/Antibiotic_prophylaxis
(I'm talking about the use in humans there)
I wouldn't take it unless I was a non monogamous gay man[0], the risks out-weights the benefits in any other demographics imho.
[0] not that I have anything against that per say, it's just statistically the most affected demographic
(Your also discounting drug users; but unfortunately those addicted and at risk are also the least likely to have the means to acquire the drug.)
Also sex workers, also trans women, also people from countries with a high prevalence of HIV in the general population.
For example there's a massive campaign targeting both men and women engaging in any sort of sexual activity that includes fluid exchange promoting usage of PrEP. One can see it in a subway and on local commercials on TV.
There's some new campaign now which unfortunately i don't quite recall but it is highly bizarre. It something along the lines of "equality. make hiv undetectable. Truvada for PrEP." or something like that.
If a drug user is doing something as stupid as sharing needles they're likely not in the right state of mind to take PrEP.
https://www.injectingadvice.com/v4/index.php/articles/harm-r...
2. Condoms are very effective and can be used in this type of situation.
Availability of PrEP coincides with a drop in condom usage:
https://www.theguardian.com/society/2018/jun/06/rapid-rise-i...
What are the chances you have the disease?
People on HN may be able to work this out, but I guarantee that many people (including doctors and nurses) can't.
See Gerd Gigerenzer's work on this in Reckoning With Risk or Risk Savvy.
1000 people take a test. 1 of them has a disease, and the test will probably return positive for that person. 999 of them do not have the disease, and the test will return positive for about 9 of them.
since all porn talent on all non-underground shoots is supposed to only engage in sex with others (on and off the set) who tested negative and since the new talent has to test negative first time weeks before the talent enters the pool even the look back tests are very effective.
Would you bet the rest of your life on a casual test like that?
On an individual level, this doesn't guarantee much, but on a population level this could provide a huge benefit. You yourself might not feel confident based on the test, but it would likely severely limit the spread of STDs (as long as treatment is available and accessible).
The main benifit of a bed-side test isn't that it informs the person who is infected. It is that it informs the person who is not infected.
Currently, most people who ask about STD status just take their partners word. Maybe a particuarly paranoid person will ask to see actual lab results, which could reasonably be months or years old at best (how often do you expect people to get tested?) or maliciously forged at worst (hopefully rare enough to be irrelevant at the population level).
With a bedside test, you get up to date information (subject to the quality of the test) on if you are about to get exposed, and can avoid the exposure if necessary.
There is still the cultural issue of needing to test your partner before an interaction, would might come across as prohibitively offensive.
HIV transmission is not so easy; last I checked, the rough odds of transmission from a single act of unprotected vaginal sex with a HIV+ partner was around 1 in 500.
If the test is 99% accurate, and your partner isn't in an obvious high risk group, it may push the odds into "less risky than other behaviors you commonly accept" territory.
For point of reference, condom use only decreases the risk by a factor of 10. Possibly less: https://www.catie.ca/en/fact-sheets/prevention/condoms
[1] https://www.healthline.com/health/hiv-aids/rate-global-diagn...
Either way, you only have to add a few more digits of risk mitigation and you're more likely to die in a car accident. A test that had even a 1% false negative rate would cover most of that ground.
That is a fairly large number of the population that would be placed on an expensive drug with several side effects.
Straight men/women can easily have it and one fuckup and you can be infected
The probability is low though, and apparently there are side effects. We also don't preemptively dish out antibiotics for similar reasons: they won't do you any good unless under very specific circumstances and you will likely experience side-effects. Do no harm.
But the plan for prep also specifically includes you going into the doctor every 3 months to not only test for those side effects but also for a full STD panel. (Source: my husband and me are both on prep)
Just saying that "at risk" people should be trying to prevent this ignores a large portion of the population to try to stop its spread.
Thankfully a vaccine is in testing now, but if this was a vaccine most people would probably not question taking it. So why is a pill to protect against something like HIV so much different?
> if this was a vaccine most people would probably not question taking it
Doctors would, or so I hope, not recommend taking a vaccine with serious side-effects without a reason. You typically don't get vaccinated for Dengue fever when traveling to Helsinki.
Maybe I should rephrase that, anyone in not in a monogamous relationship (and having sex) should at least discuss it with their Doctor and see if it would be worth them being on.
I find it shocking when I am talking to someone and find out they have no idea that prep even exists.
Anyone not in a monogamous relationship that has (unprotected) anal sex with different men.
Nothing else makes statistical sense. There is such a thing as a precautionary principle for medicine and it goes against most of what you wish to be.
What you are describing makes absolutely no sense for straight men or women that don't have unprotected anal sex.
The resistance in this article is to efavirenz and nevirapine, neither of which is used in PrEP. They're not even in the same class of drugs - both are NNRTIs, whereas PrEP consists of two NRTIs (in a single pill).
#Why -- No one is _really_ sure. The most popular hypothesis is that it happens when people go on and off the medicine. Why would people do this? Shame, access, and some mothers that went on only during pregnancy. WHO recommended a pregnancy only treatment until ~2015.
#Impact -- These resistant breeds can spread, presumably just like the other varieties. The people with it have a much worse prognosis than those without.
#PrEP -- All the other parent comments talk about it. Sure, it should be used more frequently. It's a bit of a pipe dream to see it used in the 3rd world.
Both drugs are members of the same class of anti-retrovirals, NNRTIs, which aren't prescribed together, they are two alternatives of the same type of drug and are used in combination with other drug classes.
None of the people have resistance to anti-retrovirals in general, they have resistance to a particular class which is no longer recommended in the US (as a first treatment) but is still a go-to in Africa. There are multiple other drug classes that can be put together for effective treatment.
In the US, Efavirenz (brand name Sustiva) used to be one of the first-line recommendations, but has been replaced by other drugs with fewer side effects and higher barriers to resistance.
Importantly, no currently recommended starting regimens contain a member of the NNRTI class.
All 4 of the current US recommended regimens now contain an integrase inhibitor (Dolutegravir, Bictegravir, or Raltegravir)
https://aidsinfo.nih.gov/guidelines/brief-html/1/adult-and-a...
The integrase inhibitors have exceptionally few side effects and are also very high barrier to resistance. Dolutegravir which is mentioned at the end of the article is especially good in this regard, to the point that it is the only drug currently used in an only 2 drug (vs 3 drug) combination therapy. The main thing that needs to happen is for these areas to transition off of these particular NNRTIs.
That can still make them distant? Is Australia less 'distant' from Europe now that it takes 24 hours instead of 6 weeks to get there? In some senses, yes, but not in the sense that the GP used 'distant' (i.e., as a objective word for 'not adjacent').
[...]
> People living with HIV might go on and off the drugs for several reasons.
They didn't mention the fact that in most countries for most medications people just don't take meds as they should. We see this for meds that are crucial to keep the person alive. Many organ transplants fail because the person fails to take meds correctly afterwards. We see this where patients need to pay for their meds and further treatment (the US) or where they get free meds and further treatment (the UK).
This isn't a few percent of people who take meds. It's over a third of them, maybe about half of them.
It's a big problem.
The wider and more frequently the drug is used the faster this process occurs?
There is some hope though: having a resistant trait is only useful if it helps you survive. Most resistant traits are "costly" to keep around. Thus if we stop using some treatment - completely stop - in 100 years it will likely become useful again as those "microbs" without resistance out compete those with it.
While it isn’t related to the primary focus of the parent article, it gives some useful context.
>> At the end of this first stage, the viral load stabilizes at a level that can, puzzlingly, last for many years. Doctors refer to this level as the set point. A patient who is untreated may survive for a decade with no HIV-related symptoms and no lab findings other than a persistent viral load and a low and slowly declining T cell count.
>> Eventually, however, the asymptomatic stage ends and AIDS sets in, marked by a further decrease in the T cell count and a sharp rise in the viral load. Once an untreated patient has full-blown AIDS, opportunistic infections, cancers and other complications usually cause the patient's death within two to three years.
>> The key to the mystery was in the decade-long asymptomatic stage. What was going on then? Was HIV lying dormant in the body? Other viruses were known to hibernate like that. The genital herpesvirus, for example, hunkers down in nerve ganglia to evade the immune system. The chicken pox virus also does this, hiding out in nerve cells for years and sometimes awakening to cause shingles. For HIV, the reason for the latency was unknown.
...
>> When the researchers reran the experiment, fit the data to the model's predictions and estimated its parameters again, they obtained results even more staggering than before: 10 billion virus particles were being produced and then cleared from the bloodstream each day. Moreover, they found that infected T cells lived only about two days. The surprisingly short life span added another piece to the puzzle, given that T cell depletion is the hallmark of HIV infection and AIDS.
>> The discovery that HIV replication was so astonishingly rapid changed the way that doctors treated their HIV-positive patients. Previously physicians waited until HIV emerged from its supposed hibernation before they prescribed antiviral drugs. The idea was to conserve forces until the patient's immune system really needed help because the virus would often become resistant to the drugs. So it was generally thought wiser to wait until patients were far along in their illness.
>> Ho and Perelson turned this picture upside down. There was no hibernation. HIV and the body were locked in a pitched struggle every second of every day, and the immune system needed all the help it could get and as soon as possible after the critical early period of infection. And now it was obvious why no single medication worked for very long. The virus replicated so rapidly and mutated so quickly, it could find a way to escape almost any therapeutic drug.
>> Perelson's mathematics gave a quantitative estimate of how many drugs had to be used in combination to beat HIV down and keep it down. By taking into account the measured mutation rate of HIV, the size of its genome and the newly estimated number of virus particles that were produced daily, he demonstrated mathematically that HIV was generating every possible mutation at every base in its genome many times a day. Because even a single mutation could confer drug resistance, there was little hope of success with single-drug therapy. Two drugs given at the same time would stand a better chance of working, but Perelson's calculations showed that a sizable fraction of all possible double mutations also occurred each day. Three drugs in combination, however, would be hard for the HIV virus to overcome. The math suggested that the odds were something like 10 million to one against HIV being able to undergo the necessary three simultaneous mutations to escape triple-combination therapy.
>> When Ho and his colleagues tested a three-drug cocktail on HIV-infected patients in clinical studies in 1996, the results were remarkable. The level of virus in the blood dropped about 100-fold in two weeks. Over the next month it became undetectable.
[0] https://scientificamerican.express.pugpig.com/2019/03/13/how...
"Eschew flamebait. Don't introduce flamewar topics unless you have something genuinely new to say. Avoid unrelated controversies and generic tangents."
and "Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith."
https://news.ycombinator.com/newsguidelines.html
We detached this subthread from https://news.ycombinator.com/item?id=20580974.
STI incidence among MSM using PrEP Men who have sex with men (MSM), particularly those who have indications for pre-exposure prophylaxis against HIV (PrEP), are at high risk for sexually transmitted infections (STI). In a study of nearly 3000 MSM in Australia who were initiating PrEP, the incidence of new chlamydia, gonorrhea, or syphilis over the subsequent year was 92 cases per 100 person-years [2]. Nearly half of the participants were diagnosed with an STI during the study period, with 25 percent of participants accounting for 75 percent of all STIs diagnosed; the risk of STI was proportional to the number of sexual partners and frequency of group sex. These data highlight the importance of frequent STI screening for MSM using PrEP.
2. Traeger MW, Cornelisse VJ, Asselin J, et al. Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection. JAMA 2019; 321:1380.
But as more people start using PrEP and get tested regularly due to the general requirements, it is possible that STD rates will decline, but we're probably a few years away from seeing that in the statistics.
It's a matter of having some sense of personal responsibility really.
This exact phrase was used to spin the deaths of thousands of gay men as a personal failing not many years ago. Stop doing it.
2. Some people are allergic to them
3. There are some activities that you really don't want to do with a condom
4. How about we just don't fucking shame people for not wanting to use a condom as long as both (or all) parties agree. Especially when there is a drug like prep.
Wear condoms.
Contracting HIV with unprotected sex is difficult (1/1000 for vaginal sex and insertive anal sex, 1/71 for receiving anal sex - all numbers for unprotected sex) [1], breaking a condom is also difficult (4% cases in anal sex between gay men - which is the higher number [2]). Meaning that contracting HIV while wearing a condom, is extremely difficult (0.05% in the worst hypothesis).
It's up to you then, to prove that PrEP is more efficient than 99.95% of times (while still disregarding that unlike condoms, PrEP doesn't protect you in any way from other STDs... yes, those STDs that people not using condoms and that think they are entitled to have other tax/insurance payers providing PrEP for them, are spreading around).
[1] https://www.catie.ca/en/pif/summer-2012/putting-number-it-ri... [2] https://www.ncbi.nlm.nih.gov/pubmed/27227161
That depends if it's those people bearing the full cost of buying PrEP, or if they expect the state/insurance companies to do it for them.