Reverse Transcriptase Inhibitors (RTIs) are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer.

HIV is a retrovirus because it contains genetic information in the form of RNA. When HIV infects a human cell, it uses an enzyme called reverse transcriptase to convert the single stranded viral RNA to double stranded viral DNA. The viral DNA is then integrated into the host cell’s DNA and is able to go through cellular processes, such as transcription and translation, which allow it to replicate. RTIs are used to inhibit reverse transcriptase’s enzymatic function, thus preventing HIV replication.

There are three different types of RTIs:

Nucleoside Analog Reverse Transcriptase Inhibitors (NARTIs or NRTIs)

NRTIs were the first class of antiretroviral drugs developed. They are analogues of the normally occurring deoxynucleotides, molecules that make up the structural units of RNA and DNA, needed to synthesize the viral DNA. The only difference between NRTIs and deoxynucleotides is that NRTIs are missing a hydroxyl group, an oxygen atom bonded to a hydrogen atom. NRTIs compete with the normal deoxynucleotides for a position in the growing chain of viral DNA. When NRTIs are incorporated into the viral DNA, the missing hydroxyl group inhibits DNA synthesis from properly occurring, which is called chain termination. Thus, NRTIs are referred to as competitive substrate inhibitors because they bind to reverse transcriptase, the enzyme, in order to prevent the binding of the normal deoxynucleotides, the substrate.

Some NRTIs include zidovudine (Retrovir), didanosine (Videx), stavudine (Zerit), and Epivir (lamivudine).

Nucleotide Analog Reverse Transcriptase Inhibitors (NtARTIs or NtRTIs)

NtRTIs were the second class of antiretroviral drugs developed. Normally, nucleoside analogs are converted into nucleotide analogs by body processes. Thus, taking nucleotide analogs eliminates the conversion and goes directly to the inhibiting process. NtRTIs follow the same method of competitive substrate inhibition as NRTIs.

An example of an NtRTI is Viread (tenofovir).

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

NNRTIs were the third class of antiretroviral drugs developed. NNRTIs are non-competitive inhibitors of reverse transcriptase. They work by binding to a different site compared to the NRTI or NtRTIs and are not incorporated into the viral DNA. Instead, they inhibit the movement of proteins that are essential to reverse transcriptase’s function in carrying out DNA synthesis.

Some NNRTIs include Sustiva (efavirenz), Viramune (nevirapine), Rescriptor (delavirdine), and Intelence (etravirine).