HIV and ID Observations

An email query from a colleague:

Hi Paul,
Just got a call from one of our surgeons who got a needlestick from a suture needle, small amount of blood. Patient is HCV +. Any post-exposure prophylaxis recommended?
Thanks,
Dan

The quick answer is no, it’s not recommended. From the guidelines:

But it’s a natural question to ask for several reasons — on first blush, PEP for HCV seems like a no-brainer, because:

• It works for HIV.
• There’s no vaccine.
• Rate of transmission is approximately 10-fold higher than with HIV.
• The HCV drugs are practically side-effect free.
• It feels better doing something rather than nothing.

But despite the above issues that favor PEP today for HCV occupational exposures, there is absolutely zero chance this makes sense from a cost-effectiveness perspective. It’s just not possible.

A little refresher on basic principles of cost-effectiveness analysis:  something is cost-effective if you get good value for your healthcare dollar. You spend more money, and you prolong life. How much you spend compared to standard-of-care, and how more much life you get in return gives you the numerator and denominator in that all-important cost-effectiveness ratio. In the USA, if we spend <$100,000 for an extra year of life, that’s considered cost-effective; <$50,000, very cost effective.

So let’s consider the HCV needlestick scenario, with 100 exposures; all assumptions will be biased in favor of PEP, just to make the point:

• The risk of acquiring HCV from a needlestick is 2-8%, depending on the nature of the exposure; some will clear it spontaneously. So if we do nothing, around 5 of these 100 exposures will end up with chronic HCV.
• Let’s assume that two weeks of PEP with sofosbuvir/ledipasvir will be 100% effective in preventing HCV acquisition. There are no data, but let’s give it the benefit of the doubt. And note that the HIV PEP protocol is 4 weeks, but at least one pilot study is using 2 weeks for HCV. (Why? Not sure.)
• Two weeks of PEP will cost $15,000 per patient — actually, a bit more, but let’s round it to $15K or a total of 1.5 million dollars for our 100 exposures.
• If we didn’t give PEP after the exposures, we’d need to treat the 5 people who contracted HCV with 12 weeks of sofosbuvir/ledipasvir, which would cost $450,000. All would be cured.
• The PEP strategy therefore costs $1,050,000 more than the no PEP one (1.5 million minus 450,000), and prevents 5 cases of HCV. That’s $210,000/case prevented — so a lot.
• What about survival, the denominator part of the cost-effectiveness ratio? The projected survival of those in whom HCV was prevented by PEP vs later cured with HCV treatment should be roughly the same (no one is getting cirrhosis or hepatocellular carcinoma with early treatment) — but maybe there’s some “disutility” to getting HCV, even if it’s rapidly cured. So let’s give the PEP strategy a bit of a quality-adjusted survival advantage — how about 10 weeks, since that’s the extra time on treatment for an actual case? Of course we can only apply this to the 5 cases of HCV prevented in our 100 person cohort, so it’s an overall advantage of 0.5 weeks (10 weeks times 0.05), or roughly 0.01 years.
• Finally, we arrive at our cost effectiveness ratio, which is $1,050,000/0.01 years, or $105 million/quality-adjusted life year.

More than 100 million dollars for a quality-adjusted life year? Yep. I told you it couldn’t possibly be cost-effective.

Now again, I biased everything in favor of PEP. What if it doesn’t always work? What if failures of PEP lead to resistance? What if the PEP regimen needs to be 4 weeks long? What if the quality-of-life adjustment is an overestimate? What if some of the patients who get HCV have a very low HCV RNA, and can be cured with 8 weeks, not 12?

Well, then you’d be spending even more than $105 million dollars per year of life saved. But whether it’s $105 million, or even half my back-of-the-envelope estimates (which could be wrong — I was an English major, after all), the point remains: This can’t be a cost-effective intervention.

But as I was sharing these thoughts with my brilliant friend and colleague Rochelle Walensky, who does this stuff for a living, she reminded me of this important fact:

I might encourage you to acknowledge that many of these kinds of decisions (PEP, safety of the blood supply) are not made on cost-effectiveness grounds … Most of the cost-effectiveness data for the screening for the blood supply demonstrates it’s not at all cost effective. You may want to acknowledge that point (we pay more for lots of things that cost-effectiveness suggests we shouldn’t, including keeping health workers safe given their dedication to care, keeping blood supply safe etc).

[youtube http://www.youtube.com/watch?v=RSBaEz10sQk&w=560&h=315]