HIV Boot Camp: NRTIs

HIV Boot Camp: NRTIs

Editor's note: To date, our most reader requested topic has been HIV. We've written a guest post at MedEd101 to cover the most NAPLEX-worthy testing points. But we thought we'd dig in a little further here. Over the next few weeks, we're posting a series called HIV Boot Camp. We'll shore up your HIV fundamentals. Then we'll breakdown each drug class piece by piece to highlight what you need to know. For convenience, we'll link each part of the series here. Part IPart II



Nucleoside Reverse Transcriptase Inhibitors make up what's called the "backbone" of every traditional HAART regimen. It is also an awfully long phrase to type, so I will refer to them only as "NRTIs" from here on out. 

But before I go on, there's another distinction I have to make. There are actually both nucleoside and nucelotide reverse transcriptase inhibitors. We lump them into the same "NRTI" bucket because they work in exactly the same way. But they are technically different from each other. 

I never thought my bachelors degree in Molecular Genetics would come in handy, but here goes. Let's time travel back to the stuff you learned about in your own genetics pre-pharm classes. All the way back to DNA base pairs. A DNA base pair is the A, T, G, and C that make up a DNA sequence. They also form the title of a charming movie called "GATTACA." 

In a technical sense, nucleoside is one of those DNA base pairs (A,T,G, or C) attached to a sugar.

A nucleotide is the same thing. But with a a phosphate attached to it. So you might have something like 5'-Adenosine monophosphate.

Chemically, what you have is this:

Nucleoside: Base + Sugar
Nucleotide: Base + Sugar + Phosphate

When a nucleotide loses it's phosphate through hydrolysis (or any other means), it becomes a nucleoside.

Back to our NRTIs. All of them are nucelosides....except for tenofovir. Tenofovir is the only nucelotide of the bunch. As far as I know, there is no active research into getting more NRTIs (nucleoside or nucleotide), so this is going to be the landscape for a while. 

Does any of this really matter much to you in terms of pharmacy school? No, not really. But you're here to learn right? You might win something on HIV drug trivia now. Or you can be like one of those smug people that go around correcting everyone on their english. 

Get it? Cause it's an owl. Owls say "who" ( Image )

Get it? Cause it's an owl. Owls say "who" (Image)

Anyway, that's enough "science" for now. Let's get on with it. 

How do NRTIs work?

NRTIs are designed to mimic natural nucleotides in structure, but not in function.

To try and describe how this works: imagine you run an evil corporation that makes knock-off cell phones. You go out to get some source material to make these cellphones, and some guy in a suit sell you what looks like gold and feels like gold for your circuits.

When you go and try to make your phones, the "gold" basically mucks up your systems. Your factory shuts down and you die of dysentery (for some reason) like you were on the Oregon Trail.

In the same way, NRTIs muck up reverse transcriptase by inserting themselves into the genome, but then shutting down transcription . No reverse transcription? No viral replication.

Or, to put it another way, think of when you were asked to recreate a drawing as a kid. You get that 4 crayon box with four colors (AGTC). What NRTIs essentially do is come in (like a bully) and replace the Crayola crayons you had with some plastic colored sticks that don't color at all. Now you can't recreate the drawing. You become sad, and you no longer function.

The nucleotides of art. ( Source )

The nucleotides of art. (Source)

Because crayons are life.

Or, for yet another example (because sometimes you need 3), we once made an analogy comparing NRTIs to Frodo and Sam marching undetected through Mordor to throw the One Ring into Mt. Doom and ruin Sauron's shit.

Moving on...

The downside of NRTIs is that since they mimic actual nucleotides, they can also screw up human genome replication (by screwing with DNA polymerase).

Luckily, beautiful human creatures like ourselves have built in redundancy to correct mistakes made by DNA polymerase. HIV's Reverse Transcriptase does not have said redundancy. Unfortunately, our redundancy process is not perfect and adverse effects still happen.

Let's talk about those adverse effects.

We'll start with class side effects. These are things that can occur with any NRTI.

Damage to DNA, particularly in the mitochondria (the power house of the cell!) leads to most adverse effects attributed to NRTIs. Lactic acidosis, lipoatrophy (if you don't know what this is, Google it and you will never forget), and peripheral neuropathy.

A mantra that fellow HU (#youknow) alumni will recognize is "lactic acidosis and hepatic steatosis." It was drilled in our heads by our wonderful IT2B professor. It rhymes. And it's a black box warning for every single NRTI. Remember this, and you will appreciate it when it shows up on the NAPLEX.

Moving on to individual agents, we're going to do something a little different. There are several NRTIs, and each has its own quirks. There's a lot of great resources available for HAART information. AETC (our personal fave), Aidsmap, WHO, and CDC to name a few. 

Well....we're going to give you more drug-specific information. The tl;dr way.

What you'll see in the tables below includes the pertinent dosing (and dose adjustments) you need for each agent. The tables will also highlight some important characteristics worth noting about each drug (ex. tenofovir is associated with both renal failure and osteoporosis). 

We tried to make it nice and easy by breaking things down in tables. It's not an exhaustive resource on each drug. But it's more than what you'd need for the NAPLEX (and for most practice situations). 

Do you want an HIV Cheat Sheet? 

It’s hard to even call this a cheat “sheet,” as this sucker weighs in at 16 pages. But you could call these 16 pages “Basically everything you need to know about HIV pharmacotherapy.” It’s got renal/hepatic dosing adjustments, adverse effects and clinical pearls, brand/generic/abbreviation for every drug and combination product, preferred regimens for healthy adults, pediatrics, and pregnancy, opportunistic infection prophylaxis and treatment, adult and pediatric dosing tables, drug-drug interactions, drug-food interactions, and (seriously) a lot more.

This cheat sheet will save you a ton of time and frustration as you prep for the NAPLEX or any time you come across HIV in your practice.

It’s yours for only $19.


The Drugs

Editor's Note: You'll notice as you go through these tables that the three-letter abbreviations are used for each drug. While it's not absolutely necessary to know the three-letter abbreviation for each HAART medication, it is incredibly helpful. You'll find that most literature and HAART resources use the abbreviations.

Most abbreviations make sense and follow some sort of rhyme/reason. Others (3TC, FTC and d4T I'm looking at you), unfortunately don't seem to have much of a naming scheme. You'll just have to memorize those. 

Anyway, we'll be using the abbreviations throughout the rest of HIV Boot Camp. So consider this a heads up. Again, they're not completely necessary to commit to memory...but they will make your life easier if you do.  

Tenofovir Disoproxil Fumarate (Viread)


Standard Dosing 300mg QDaily Preg: B
Renal Dosing
CrCl (mL/min) Dose
30 – 49 300mg Q48
10 – 29 300mg Q72 or Q96
Dialysis 300mg Q7D or 12H Post-Dialysis
Hepatic Dosing N/A
Notes ADRs of Note:
  • Fanconi syndrome (TDF will F' up kidneys)
  • Acute renal failure (again, F' up kidneys)
  • Decreases bone mineral density (osteopenia/osteoporosis)
ART Interactions:
  • ddI levels increased
  • ATV levels decreased (must boost ATV)
  • ATV/r DRV/r LPV/r all increase tenofovir concentrations

As noted earlier, TDF is the only nucleotide of the bunch.

TDF is also used for Hepatitis B (HBV) treatment so avoid abrupt withdrawal if treating HBV or HIV/HBV-infected.

Tenofovir alafenamide (TAF) is found in combinations, but the single drug formulation is used only for HBV (Vemlidy).

Emtricitabine (Emtriva)


Standard Dosing 200mg Capsule QDaily
240mg Solution QDaily
Preg: B
Renal Dosing
CrCl (mL/min) Capsule Solution
30 – 49 200mg Q48 120mg QDaily
15 – 29 200mg Q72 80mg QDaily
<15 or Dialysis 200mg Q96 60mg QDaily
Hepatic Dosing N/A

ADR of Note:

  • Hyperpigmentation of palms/soles (aka: palmar/solar rash) (aka: hand and foot syndrome)
  • Hypersensitivity reaction

FTC also covers Hepatitis B, so avoid abrupt withdrawal in patients with (HBV) due to possible flares.

Structurally similar to Lamivudine (Epivir, 3TC). They're like cousins. So avoid the combination. Cause that's just weird. This also means that if HIV gets resistant to FTC, then it is also resistant to 3TC.

Lamivudine (Epivir)


Standard Dosing 300mg QDaily
148mg BID
Preg: C
Renal Dosing
CrCl (mL/min) Dose
30 – 49 148mg BID
300mg QDaily
15 – 29 148mg Once, 100mg QDaily
5 – 14 148mg Once, 100mg QDaily
<5 48mg Once, 25mg QDaily
Hepatic Dosing N/A

Avoid abrupt withdrawal in patients with Hepatitis B infection (HBV) due to possible HBV flares (that's right, it also covers HBV).

Goes to the same family reunion as Emtricitabine (Emtriva, FTC). In fact, they ran into each other at an Easter gather up this past year. So again, don't use them together in your HAART regimen.

Abacavir (Ziagen)


Standard Dosing 300mg BID
600mg QDaily
Preg: C
Renal Dosing

No renal adjustments here. This is the only NRTI that does not require a renal adjustment

But do note: Alcohol dehydrogenase is the mechanism of choice, so if anything no drinky and abacaviry. Alcohol can raise levels by 41%.

Hepatic Dosing Child-Pugh Class A: 200mg BID

HLA-B*5701 testing is required. This is one of the very few HLA tests required by the FDA prior to treatment (For the love of everything Holy, please remember this on the NAPLEX). If the test comes back positive, DO NOT GIVE ABACAVIR.

Abacavir can cause hypersensitivity reactions that lead to organ failure and death. Being HLA-B*5701 positive predisposes a patient to the reaction.
If someone develops a reaction, stop and DO NOT RECHALLENGE.

HIV RNA >100,000 copies? Don’t use ABC unless with dolutegravir. Dolutegravir is Abacavir’s bathroom buddy. You'll find them together (along with lamivudine) in the combination product Triumeq.

Didanosine (Videx EC)


Standard Dosing
Body Weight (BW) Dose
<60 kg 248mg QDaily
125mg BID
>60 kg 400mg QDaily
200 mg BID
Preg: B
Renal Dosing Capsules
CrCl (mL/min) BW <60 kg BW >60kg
30 – 59 125mg QDaily 200mg QDaily
10 – 29 125mg QDaily 125mg QDaily
<10 or Dialysis POWDER 125mg QDaily

CrCl (mL/min) BW <60 kg BW >60kg
30 – 59 148mg QDaily
75mg BID
200mg QDaily
100mg BID
10 – 29 100mg QDaily 148mg QDaily
<10 or Dialysis 75mg QDaily 100mg QDaily
Hepatic Dosing N/A

Not commonly used today, because it's side effect profile sucks. It has a similar side effect profile as Stavudine (Zerit, d4T) . Both have documented neuropathy, fatal hepatic events and pancreatitis. So don't use them together. Also note that Didanosine and Stavudine are the only HAART medication with a weight-based dosing. That's just begging to show up on a test somewhere...

Save the pancreas.

Stavudine (Zerit)


Standard Dosing
Body Weight (BW) Dose
<60 kg 30mg BID
>60 kg 40mg BID
Preg: B
Renal Dosing
CrCl (mL/min) BW <60 kg BW >60kg
26 – 48 15mg BID 20mg BID
10 – 25 or Dialysis 15mg QDaily 20mg QDaily
Hepatic Dosing N/A

There's that weight-based dosing again. Similar ADR profile as Didanosine (Videx EC, ddI) and again, documented neuropathy, fatal hepatic events and pancreatitis.

Avoid concurrent use, and avoid using this one with Zidovudine (Retrovir, AZT/ZDV).

Zidovudine (Retrovir)


Standard Dosing 300mg BID
200mg TID
Preg: C
Renal Dosing Dialysis: 100mg Q6-8
Hepatic Dosing N/A

ADRs of Note:

  • Hyperpigmentation of skin/nails
  • Myelosuppresion (anemia, neutropenia)
  • Myopathy

This one is a doozy. It's also known as azidothymidine (hence the AZT shorthand...don't get this mixed up with azathioprine). It was the first HAART medication approved in the US (this is what they're talking about in the musical "Rent" when they say "AZT Break"). Of note, it has an IV formulation available. This makes it one of only two HIV medications available parenterally (the other being enfuvirtide, which is administered subcutaneously).

Avoid with Stavudine (Zerit, d4T).





Combivir (3TC + AZT/ZDV) Lamivudine
<48mL/min – Avoid
Epzicom (ABC + 3TC) Abacavir
<48mL/min – Avoid
HLA-B*5701 testing required
Trizivir (ABC + 3TC + AZT/ZDV) Abacavir
<48mL/min – Avoid
HLA-B*5701 testing required
Truvada (FTC + TDF) Emtricitabine
Tenofovir Disoproxil Fumarate
30-49 mL/min – 1T Q48
<30 mL/min – Split Components
Descovy (FTC + TAF) Emtricitabine
Tenofovir Alafenamide
Renal: <30mL/min – Avoid
Cimduo (3TC + TDF) Lamivudine
Tenofovir Disoproxil Fumarate
Renal: <50mL/min – Avoid

The pharmacy profession is moving on...with or without you

The pharmacy profession is moving on...with or without you

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