Editing Reverse-transcriptase inhibitor (section)

===Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs){{anchor|Nucleoside analog reverse-transcriptase inhibitor}}<!-- This is a more generic anchor. -->===
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.<ref name=sidee>{{cite journal | first1=Yann-Erick |last1=Claessens |first2=Jean-Daniel |last2=Chiche |first3=Jean-Paul |last3=Mira |first4=Alain |last4=Cariou| title = Bench-to-bedside review: Severe lactic acidosis in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors| journal = Critical Care| date = 2003 |volume=7 |issue=3 |pages=226–232 |doi=10.1186/cc2162 | pmid = 12793872|pmc=270672 |doi-access=free }}</ref>
* [[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 [[HIV/AIDS|AIDS]], [[hepatitis C]], and [[SARS-CoV-2]]

====Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs){{anchor|Nucleotide analog reverse-transcriptase inhibitor}}<!-- This is a more generic anchor. -->====
As described above, host cells [[phosphorylation|phosphorylate]] [[nucleoside]] analogs to [[nucleotide]] analogs. The latter serve as poison building blocks ([[chain termination|chain terminators]]) for both viral and host DNA, causing respectively the desired [[antiviral drug|antiviral effect]] and [[Adverse effect#Medications|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 Sciences|Gilead]].{{cn|date=November 2022}}
* [[Tenofovir]], also known as TDF is a so-called 'prodrug' with the active compound deactivated by a molecular side chain that dissolves in the human body allowing a low dose of tenofovir to reach the site of desired activity. One example of the prodrug form is tenofovir disoproxil fumarate with the trade name Viread (Gilead Sciences Inc USA). It is approved in the US for the treatment of both HIV and hepatitis B.
* [[Adefovir]], also known as ADV or bis-POM PMPA, has trade names Preveon and [[Hepsera]]. It is not approved by the FDA for treatment of HIV due to toxicity issues, but a lower dose is approved for the treatment of hepatitis B.

While often listed in chronological order, NRTIs/NtRTIs are nucleoside/nucleotide analogues of cytidine, guanosine, thymidine and adenosine:{{cn|date=November 2022}}
* Thymidine analogues: [[zidovudine]] (AZT) and [[stavudine]] (d4T)
* Cytidine analogues:  [[zalcitabine]] (ddC), [[lamivudine]] (3TC), and [[emtricitabine]] (FTC)
* Guanosine analogues: [[abacavir]] (ABC) and [[entecavir]] (ETV)
* Adenosine analogues: [[didanosine]] (ddI), [[tenofovir]] (TDF), and [[adefovir]] (ADV)