The Case of the Disappearing Protease Inhibitors

They were supposedly the end of AIDS — why are they so infrequently prescribed today?

This is in some sense the second in a series of posts I began with The Drugs Don’t Work. I would note that this is very introductory and will certainly be enhanced and updated in the coming months. This oddity we’ll discuss today represents one more piece of the puzzle that is the motivation behind the “anti-HIV medication” scheme that is not only ongoing today, but is actively trying to get these “anti-HIV drugs” into as many HIV-negative people as possible as well via PrEP.

I have to admit that until I fell entirely by accident into covering PrEP and the Truvada disaster, I was not all that interested in the specifics of so-called anti-HIV medication. I was more interested in a meta, philosophy of science kind of way as to why this paradigm can’t logically be true. That all changed when I began to look into PrEP and Truvada, and one thing that I have learned that is very weird to me is that among the most commonly prescribed multi drug therapies for HIV, very few of them contain a protease inhibitor at all. (As an added bonus, I’ve discovered that learning these specifics actually enhances the “meta” understanding of the whole thing.)

If you are as old as I am, you recall that David Ho was named Time’s Person of the Year in 1996 for his papers endorsing protease inhibitors and “hit hard, hit early” antiretroviral therapy. It was in that year that the first protease inhibitor, ritonavir (one half of Paxlovid), was approved. If you recall, the protease inhibitors were heralded as a miracle that had ended AIDS. Why are they barely being used any longer? It’s interesting to me that there are only five FDA approved protease inhibitors, of over thirty “anti-HIV” drugs, and that only one of them, ritonavir, was approved before 2003.

It can’t be because we have such great, new and improved drugs (most of which have been developed “in silico,” which is highly suspicious), because in almost every single multi drug therapy for HIV is at least one, and sometimes two, nucleoside analogue drugs, which as you recall is the class of drugs to which the OG AIDS drug, the notorious AZT, belongs.

The rest of this post will be a bit technical, because I will discuss every medication that is currently FDA approved for HIV, with particular attention to the components of the multi drug therapies, but I think that this is important information for us to have. It seems very strange indeed to me that the very drugs that supposedly ended the AIDS epidemic are no longer in use, and it certainly isn’t thanks to a vaccine. Note also that since this post mostly refers to FDA approval, this post refers primarily to drugs with such approval, but given how much AIDS funding the U.S. funnels to other countries, I’m sure their information is applicable in most places.

Here is the document I will be referencing:

FDA Approved HIV Medicines

Before we get started, I would like to remind you of the different classifications we have for “anti-HIV” drugs. I will include their abbreviation as well as the year of first approval. We have nucleoside analogue reverse transcriptase inhibitors (NRTIs; 1987); non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs; 1998); protease inhibitors (PIs; 1996); fusion inhibitors (FIs, there is only one; 2003); CCR5 antagonists (only one; 2007); integrase strand transfer inhibitors (INSTIs; 2007); attachment inhibitors (AIs, only one; 2020); post-attachment inhibitors (PAIs, only one; 2018); capsid inhibitors (CIs, only one; 2022); and pharmacokinetic enhancers (PEs, only one; 2014, although the protease inhibitor ritonavir is often used now as a PE.)

Here are the multi drug therapies. There are 22 of them, all but two of which include at least one nucleoside analogue inhibitor, but only 5 of which include a protease inhibitor. The formulations that contain a protease inhibitor are indicated with an asterisk (there are 5), and the formulations that contain either “good Truvada” (Descovy; which has its own serious adverse effects) or “bad Truvada” are bolded (there are 12.)

Epzicom - abacavir and lamivudine, NRTIs

Triumeq - two NRTIs, abacavir and lamivudine, and an ISTI, dolutregavir

Trizivir - abacavir, lamivudine, and zidovudine (otherwise known as AZT!!!!) - all NRTIs

Evotaz* - atazanavir (a protease inhibitor) and cobicistat, a “pharmacokinetic enhancer.” This seems an unorthodox combination.

Biktarvy - Biktregavir is not actually listed in the approved medications column, which must be some kind of error. Never mind, it’s an integrase strand inhibitor, per Wikipedia. It contains TAF and emtricitabine, both NRTIs. This is one formulation used in PrEP.

Cabenuva - cabotegravir (ISTI) and rilpivirine (an NNRTI)

Prezcobix* - darunavir (a protease inhibitor) and cobicistat, a PE

Symtuza* - darunavir, cobicistat, emtricitabine, and TAF (PI, PE, two NRTIs)

Dovato - lamivudine (NRTI), and an integrase strand inhibitor, dolutregavir

Juluca* - dolutregavir (PI) and rilpivirine (NNRTI)

Delstrigo - doravirine (NNRTI), lamivudine, and TDF (NRTIs)

Atripla - efavirenz (NNRTI), emtricitabine, and TDF (NRTIs)

Symfi - efavirenz (NNRTI), lamivudine, and TDF (NRTI) (also Symfi Lo)

Genvoya - elvitegravir (not listed, but it’s an ISTI), cobicistat (PE), emtricitabine, and TAF (NRTIs)

Stribild - elvitegravir (ISTI), cobicistat (PE), emtricitabine, and TDF (NRTIs)

Odefsey - emtricitabine , rilpivirine, and TAF (two NRTIs and one NNRTI)

Complera - emtricitabine , rilpivirine, and TDF (Does anyone else notice how close “Complera” is to “compliant?”) (two NRTIs and one NNRTI)

Descovy -emtricitabine and TAF (NRTIs, also used in PrEP)

Truvada - emtricitabine and TDF (NRTIs, also used in PrEP)

Cimduo - lamivudine and TDF (NRTIs)

Combivir - lamivudine and zidovudine (AZT) (NRTIs)

Kaletra* - lopinavir and ritonavir (both PIs)

I believe the most popular “anti-HIV” medication now is Biktarvy. Genvoya, Atripla, Dovato, Triumeq, Cabenuva (the injectable), and of course Truvada and Descovy are also by far among the most popular of these medications. What do we notice about these drugs? Besides Cabenuva, which does not contain an NRTI but does contain an NNRTI, they all include at least one NRTI, which you’ll recall is the “older, outdated” class of drugs. But the truly shocking thing is that not one of them contains a protease inhibitor. Not one. And do we even hear about Evotaz, Prezcobix, Symtuza, Juluca, or Kaletra?

A visit to AIDSMap (a U.K. site) indicates that initial treatment consist of a backbone of two NRTIs and another medication, usually an ISTI but in some situations a PI. The drugs recommended are Biktarvy, Dovato, Triumeq, Descovy, and a medication containing a PI called Tivicay that is used in the U.K. Drugs containing PIs are more frequently used when changing treatment while undetectable (defined as “below 50 copies of HIV RNA”—how is that “undetectable” if it can be detected?), but they are nowhere near universally used.

It’s possible that these medications are not frequently prescribed any longer because of the liver and cardiovascular toxicities patients experienced while taking them, which should cause concern. Recall from this week’s post on Paxlovid that the “HIV” protease inhibitor, ritonavir, is included as a “pharmacokinetic enhancer” to increase concentration of the other active ingredient in the liver, which seems like a wildly dangerous concept. (In fact, ritonavir is not used as a PI for “HIV” at all anymore; it is used as a pharmacokinetic enhancer.) As stated in Medical News Today:

The FDATrusted Source notes that protease inhibitors can also cause serious liver problems and increase bleeding in individuals with hemophilia, a condition in which the blood does not clot as it should.

This post has only scratched the surface of this topic, and I will be investigating further, but I want to leave you with a thought to contemplate and weigh in on. The all too perfect HIV AIDS story basically claims that the approval of ritonavir in 1996–after which it was not until 2003 that the next PIs were approved—ended AIDS. Yet the NRTIs, which are the oldest class of drugs and the ones that the PIs were claimed to have WILDLY improved upon, are included in every major combination therapy today, whereas the PIs are barely used any longer. Someone please make this picture make sense.

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