A Nucleoside reverse transcriptase inhibitors (NRTI) medication works by tricking reverse transcriptase into thinking it is one of these molecular building blocks. However, it is just different enough that when used to create DNA, NRTIs actually stop the DNA from being made. Without DNA, HIV cannot multiply.

When HIV infects a CD4 cell in a person's body, it copies its own genetic code into the cell's DNA. In this way, the cell is then "programmed" to create new copies of HIV. HIV's genetic material is in the form of RNA. In order for it to infect CD4 cells, it must first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this process.

NRTIs, sometimes called "nucleoside analogues" or "nukes," contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to convert RNA to DNA. When reverse transcriptase uses these faulty building blocks, the new DNA cannot be built correctly. In turn, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell and prevents the cell from producing new virus. While nucleotide analogues (Viread is the only nucleotide analogue approved at this time) are technically different than nucleoside analogues, they act very much the same way. In order for nucleoside analogues to work, they must undergo chemical changes (phosphorylation) to become active in the body. Nucleotide analogues bypass this step, given that they are already chemically activated.