Nucleoside analogue reverse transcriptase inhibitors (NRTIs)

Nucleoside analogue reverse transcriptase inhibitors (NRTIs) were the first antiretroviral drugs to be developed. Nucleoside analogues are synthetically created to mimic naturally occuring nucleotides. Nucleosides resemble nucleotides but they lack a phosphorus group. Nucleosides are administered because they are more easily transported across the cell membranes than nucleotides. To be active, the body must phosphorylate the nucleoside within the cell. Once phosphorylated, the analogue nucleotide can be incorporated into a DNA or RNA chain.

NRTIs work by competing with naturally occurring nucleotides. NRTIs are similar enough to be recognized by reverse transcriptase and added to the DNA chain, but the the NRTI contains an intentional error that prohibits attachment of a subsequent nucleotide to the DNA chain. NRTIs cause DNA chain termination that stop the completion of viral DNA necessary for viral reproduction.

Drugs in this class are associated with lactic acidosis, hepatic steatosis, and lipodystrophy.

Generic name
Adverse effects

Serious hypersensitivity reactions (fever, myalgia, malaise, nausea, vomiting, symptoms suggestive of upper respiratory tract infection, anorexia) linked to the presence of the HLA-B*57:01 allele, rash, headache, diarrhea, nausea, vomiting (DNV).


Pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia and hepatic dysfunction


Headache nausea, insomnia


Headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough.


Peripheral neuropathy, lactic acidosis, hepatitis, liver failure

Diarrhea, nausea, asthenia, renal insufficiency

Fatigue, headache, nausea, and vomiting, anemia, neutropenia, hyperpigmentation

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NRTIs work by substituting a synthetic nucleotide, causing a DNA chain termination