Q and A


What is the difference between NRTIs and NNRTIs?


Firstly thank you all for maintaining such a very useful service. I do not know where I would be without you. In a space with less information, encouragement and support for certain.

My question relates to my medication and how it works.

I have read your


Thank you for your question.

It is great to hear that you are interested in finding out more about your medications and how they work.

The questions you are asking involve a lot of science but I will try to answer you in a non-technical way. If there are any further questions then please do e-mail back or ask for clarifications.

To be able to answer your questions about NNRTIs (non-nucleoside reverse transcriptase inhibitors) and NRTIs (nucleoside reverse transcriptase inhibitors) let me first start by explaining what a nucleoside is and how reverse transcriptase works.

A nucleoside is the building block to our DNA and RNA. DNA is the genetic code which makes us what we are. It is what determines if we have blue eyes or a wonky nose, what we look like and to some people, if we are susceptible to any genetic medical conditions.

Our body is constantly renewing itself and making new cells. To do this the DNA (double-stranded) splits apart to become RNA (single-stranded). It is a bit like a zip opening. The single-stranded RNA then goes on to become the proteins that make up our skin, organs, hair, nails etc. HIV alone is not able to replicate. It has to put its own genetic material into our genetic material so that we can replicate the parts of the virus ourselves.

HIV only contains RNA and so needs to change its RNA into DNA to be able to integrate with our DNA for replication. To do this it has to first change its RNA to DNA. HIV uses a compound called reverse transcriptase to convert its RNA to DNA. Think of it like a zip opening to make single-stranded RNA and closing to make double-stranded DNA. In this case, reverse transcriptase is like the bit at the bottom of a jacket where you insert one part of a zip to meet the other part of the zip to allow the zip to close.

Reverse transcriptase is not found in human cells without HIV. Without reverse transcriptase HIV cannot replicate so it is a good target for anti-HIV drugs.

Both the NRTIs and the NNRTIs interact with the reverse transcriptase to stop it working. This stops HIV replicating so the amount of virus in the body will go down.

The difference between NNRTIs and NRTIs is how they stop reverse transcriptase from working. Think again of the zip. NRTIs work in different ways but one of the main ways is to compete with reverse transcriptase for their interaction site with HIV genetic material. This is like trying to zip up a jacket with more than one sets of zips. So NRTIs are like another zip giving the zipper another track to follow.

NNRTIs work by sitting in a binding site in the virus structure and this is a bit like having an object that blocks the teeth of the zipper, so the zipper cannot get past the block.


  1. BEEKA

    Thanks for the explanation given, as it is understood.

  2. Marin

    Your answers are very simplified! Thank you so much.

  3. Melanie

    Thanks for the explanation, it was very helpful!!

  4. Priscilla

    Thanks a lot for the simplified explanation

  5. Rodney

    Virology of HIV and the work of ARVs. It can be well understood. Thanks

  6. kelly

    thanks… I understand this now

  7. sudheer

    very easy to understand Thanks a lot

  8. Rebecca McDowall

    Hi Wycliffe,
    We have updated the information above to include an explanation of NNRTIs. I hope this is helpful.

    PIs work at a different stage of the HIV replication process. If NNRTIs and NRTIs don’t block HIV from converting from RNA (1 side of the zip) to DNA (the closed zip) then HIV is able to integrate into our DNA inside our CD4 cells. Once it has done this it can ‘hide’ inside our cells for many years, unless the cell is activated.

    If a CD4 cell is activated when it contains HIV DNA then this ‘wakes up’ the HIV. HIV then uses the enzymes (catalysts) in our cells to create the new RNA material needed to make new HIV.

    This new RNA creates all of the different proteins needed to create a new HIV virus. But the proteins it creates are in long strings, which are too big to create the new virus. This is where protease comes in. Think of protease like a pair of scissors which HIV uses to cut these strings of proteins into the right size to make a new HIV virus.

    Protease inhibitors work at this stage of the viral replication. They act as a block, getting in the way of the protease scissors, and stopping HIV RNA from being cut into the right size for making new HIV viruses.

    Understanding how HIV replicates, and how the different drugs work, can be very complicated. Try watching this video for a visual explanation.

  9. wycliffe

    could you explain the PIS and NNRTIS the same simple way you did the NRTI

  10. haneeya

    oh this was very much helpful!! thanks alot!!


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