therefore classified as non-competitive inhibitors of reverse transcriptase. Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs) Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs) compose the first class of antiretroviral drugs developed. In order to be incorporated into the viral DNA, NRTIs must be activated in the cell by the addition of three phosphate groups to their deoxyribose moiety, to form NRTI triphosphates. This phosphorylation step is carried out by cellular kinase enzymes. NRTIs can induce mitochondrial impairment that leads to a number of adverse events, including symptomatic lactic acidosis. Zidovudine, also called AZT, ZDV, and azidothymidine, has the trade name Retrovir. Zidovudine was the first antiretroviral drug approved by the FDA for the treatment of HIV. Didanosine, also called ddI, with the trade names Videx and Videx EC, was the second FDA-approved antiretroviral drug. It is an analog of adenosine. Zalcitabine, also called ddC and dideoxycytidine, has the trade name Hivid. This drug has been discontinued by the manufacturer. Stavudine, also called d4T, has trade names Zerit and Zerit XR. Lamivudine, also called 3TC, has the trade name Zeffix and Epivir. It is approved for the treatment of both HIV and hepatitis B. Abacavir, also called ABC, has the trade name Ziagen, is an analog of guanosine. Emtricitabine, also called FTC, has the trade name Emtriva (formerly Coviracil). Structurally similar to lamivudine, it is approved for the treatment of HIV and undergoing clinical trials for hepatitis B. Entecavir, also called ETV, is a guanosine analog used for hepatitis B under the trade name Baraclude. It is not approved for HIV treatment. Truvada, made of emtricitabine and tenofovir disoproxil fumarate, is used to treat and prevent HIV. It is approved for HIV prevention in the US and manufactured by Gilead. Azvudine, also called RO-0622. It has been investigated as a possible treatment of AIDS, hepatitis C, and Sars-Cov-2 Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs) As described above, host cells phosphorylate nucleoside analogs to nucleotide analogs. The latter serve as poison building blocks (chain terminators) for both viral and host DNA, causing respectively the desired antiviral effect and drug toxicity/side effects. Taking phosphonate nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs) directly obviates the initial phosphorylation step, but host enzymes must still phosphorylate the phosphonate nucleotide analogue to the phosphonate-diphosphate state for anti-viral activity. These molecules were first synthesized by Antonin Holy at the Czech Academy of Sciences, and commercialized by Gilead. Tenofovir,