Zidovudine Emtricitabine

Tenofovir + Emtricitabine Zidovudine + Lamivudine Abacavir + Lamivudine Efavirenz or Nevirapine Lopinavir/r or Atazanavir/r or Eosamprenavir/r or Saquinavir/r... 

Preferred regimen Efivarenz Atazanavir + ritonavir Fosamprenavir + ritonavir Lopinavir/ ritonavir Tenofovir/ emtricitabine Zidovudine/ lamivudine... 

EMTRICITABINE ZIDOVUDINE Possibly t adverse effects T bioavailability of zidovudine Watch for adverse effects of zidovudine... 

At present there are seven NRTIs, which have been formally approved for the treatment of AIDS 3 -azido-2, 3 -dideoxythymidine (AZT, zidovudine), 2, 3 -dideoxyinosine (ddl, didanosine), 2, 3 -dideoxycytidine (ddC, zalcitabine), 2, 3 -didehydro-2, 3 -dideoxythymidine (d4T, stavudine), (—)-L-3 -thia-2, 3 -dideoxycytidine (3TC, lamivudine), cyclopentenyl V -cyclopropylaminopurine (abacavir, ABC), and (—)-L-5-fluoro-3 -thia-2, 3 -dideoxycytidine ((—)FTC, emtricitabine) (De Clercq 2004a) (Fig. 3). 

Zidovudine Didanosine Stavudine Lamivudine Abacavir Tenofovir Emtricitabine Nevirapine Efavirenz TMC125 Saquinavir Indinavir Lopinavir Fosamprenavir Atazanavir Tipranavir Darunavir Raltegravir Elvitegravir Enluvirtide Maraviroc Vicriviroc Bevirimat... 

Atazanavir or fosamprenavir or nelfinavir or saquinavir/ ritonavir, and zidovudine or stavudine or tenofovir or abacavir or didanosine, and lamivudine or emtricitabine... 

Triple NRTI therapy is recommended only when a first-line or alternative first-line therapy with either an NNRTI-based or Pi-based regimen cannot be used. Abacavir plus zidovudine plus lamivudine is the only regimen approved by the DHHS. The following triple nucleoside therapy combinations have shown poor or limited efficacy, and should be avoided abacavir plus tenofovir plus lamivudine (or emtricitabine), and didanosine plus tenofovir plus lamivudine (or emtricitabine). 

Drugs that should not be combined due to overlapping toxi-cities include amprenavir oral solution plus ritonavir oral solution, atazanavir plus indinavir (due to enhanced hyperbilirubinemia), and any combination of didanosine, stavudine, and zalcitabine. Emtricitabine and lamivudine should not be combined because of their similar chemical structures, and antagonism can result when lamivudine is combined with zalcitabine, or stavudine is combined with zidovudine. 

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

Lopinavir/ritonavir or atazanavir/ritonavir and (zidovudine or fosamprenavir/ritonavir or tenofovir) and (lamivudine or emtricitabine). 

Current recommendations for treating HIV infection advocate a minimum of three antiretroviral agents. The typical regimen consists of two NtRTIs and either a ritonavir-boosted PI or NNRTI. The dual NtRTI backbone should include tenofovir plus emtricitabine (coformulated as Truvada) or zidovudine plus lamivudine (coformulated as Combivir). Abacavir plus lamivudine is an alternative. Recommended initial NtRTIs include atazana-vir-ritonavir, lopinavir-ritonavir, or fosamprenavir-ritonavir. Efavirenz is the recommended NNRTI except for women who plan to become pregnant or who do not have adequate contraception. 

The present NRTIs available for the treatment of HIV are zidovudine (azidothymidine, AZT), stavu-dine (d4T), didanosine (ddl), lamivudine (3TC), dideoxycytidine (ddC, zalcitabine) and abacavir, emtricitabine and tenofovir disoproxil. Combination formulations are abcavir combined with zidovudine and lamivudine and the abacavir-lamivudine combination. 

TC Lamivudine ABC Abacavir d4T Stavudine ddC Zalcitabine ddl Didanosine TDF Tenofovir ZDV Zidovudine, also abbreviated as AZT FTC Emtricitabine NVP Nevirapine DLV Delavirdine EFV Efavirenz RTV, r Ritonavir Pl/r Ritonavir boosted protease inhibitor SQV Saquinavir IDV Indinavir LPV Lopinavir NEV Nelfinavir APV Amprenavir ATV Atazanavir DRV Darunavir... 

Zidovudine (ZDV or AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) and it was the first anti-HIV agent to be introduced. Other NRTIs include stavudine (d4T), lamivudine (3TC), didano-sine (ddl), abacavir (ABC) and zalcitabine (ddC). Recent additions to this class are emtricitabine (FTC) which has a molecular structure similar to 3TC and tenofovir (TDF) a nucleotide reverse transcriptase inhibitor. 

Zidovudine, lamivudine Didanosine, emtricitabine, stavudine, abacavir... 

Gallant JE, DeJesus E, Arribas JR, Pozniak AL, et al. 2006. Tenofovir DF, Emtricitabine and Efavireuz vs. Zidovudine, Lamivudine and Efavirenz for HIV. NEJM. 354 251-260. 

A number of currently prescribed NRTIs are shown in Figure A.44. Compounds A.155 through A.158 are all analogues of pyrimidine nucleosides. Compounds A.159 and A.160 are both purine nucleoside analogues. Abacavir (Ziagen, A.160) is inactive until it is metabolized to carbovir (A.161) in vivo. The seven drugs in Figure A.44 were approved in the United States over a span of more than 25 years. Zidovudine reached the market first in 1987, and emtricitabine was the last to be approved in 2003. The steady release... 

Based on data from clinical trials, either an NNRTl-based or Pl-based regimen should be offered to antiretroviral-naive patients for whom therapy is indicated. The preferred NNRTl-based regimen includes efavirenz and two NNRTls either lamivudine or emtricitabine plus zidovudine or tenofovir. 

Preferred Pl-based regimens are lopinavir/ritonavir plus lamivudine or emtricitabine plus another NRTI, usually zidovudine, stavudine or abacavir. Alternative combinations include other Pis with or without ritonavir, and two NRTIs. The combination of a protease inhibitor with ritonavir provides inhibition of cytochrome p450 enzymes and permits less frequent dosing of amprenavir, indinavir, lopinavir and saquinavir. Use of ritonavir in this setting is also known as boosting. ... 

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of medications approved for the management of HIV infection. They are structural analogues of nucleic acids. They undergo intracellular phosphorylation to a triphosphate metabolite and it is this metabolite that is pharmacologically active against reverse transcriptase. Drugs in this class include abacavir, adefovir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine. 

Despite their widespread clinical use, direct nephrotoxicity has not been reported with zidovudine, emtricitabine or didanosine. Electrolyte disorders have been described but are uncommon. Hypokalemia was reported in didanosine treated patients, which may have been related to HIV infection or didanosine related diarrhea in somes though, hypokalemia occurred without diarrhea [77]. Symptomatic hypocalcemia, without changes in serum magnesium, phospho-... 

Lamivudine -I- Stavudine Lamivudine -I- Zidovudine Lamivudine + Stavudine + Efavirenz Lamivudine -I- Stavudine + Nevirapine Lamivudine -I- Zidovudine + Efavirenz Lamivudine -I- Zidovudine + Nevirapine Lamivudine -I- Zidovudine + Abacavir Tenofovir -I- Emtricitabine... 

Nevirapine plus (lamivudine or emtricitabine) plus zidovudine (or stavudine or didanosine)... 

Atazanavir plus lamivudine (or emtricitabine) plus zidovudine (or stavudine) Indinavir-ritonavir plus lamivudine (or emtricitabine) plus zidovudine (or stavudine) Lopinavir-ritonavir p/us emtricitabine plus zidovudine (or stavudine)... 

ABBREVIATIONS EFV, efavirenz 3TC, lamivudine AZT, zidovudine TDF, tenofovir disoproxil fumarate d4T, stavudine LPV/r, lopinavir/ritonavir coformulation FTC, emtricitabine NVP, nevirapine ddl, didanosine ATV, atazanavir fosAPV, fosamprenavir RTV, ritonavir IDV, indinavir NFV, nelfinavir SQV, saquinavir. 

Parameter Zidovudine Lamivudine Stavudine Didanosine Abacavir Zalcitabine Tenofovir Emtricitabine... 

FIGURE 50-3 Intracellular activation of nucleoside analog reverse transcriptase inhibitors. Drugs and phosphory-lated anabolites are abbreviated the enzymes responsible for each conversion are spelled out. The active antiretroviral anabolite for each drug is shown in the blue box. Key ZDV, zidovudine d4T, stavudine ddC, dideoxycytidine FTC, emtricitabine 3TC, lamivudine ABC, abacavir ddl, didanosine DF, disoproxil fumarate MP, monophosphate DP, diphosphate TP, triphosphate AMP, adenosine monophosphate CMP, cytosine monophosphate dCMP, deoxycytosine monophosphate IMP, inosine 5 -monophosphate PRPP, phosphoribosyl pyrophosphate NDR, nucleoside diphosphate. 

High-level host resistance to emtricitabine occurs with the same mutation (Ml84V) that affects lamivudine sensitivity, although the mutation apparently occurs less frequently. This mutation restores sensitivity to zidovudine. 

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