Efavirenz, emtricitabine, tenofovir

Abacavir (Ziagen) Amprenavir (Agenerase) Delavirdine (Rescriptor) Didanosine [ddl] (Videx) Efavirenz (Sustiva) Efavirenz/Emtricitabine/ Tenofovir (Atripla) Fosamprenavir (Lexiva)... 

Increased risk of nephrotoxicity with cidofovir, aminoglycosides, carbopla-tin, cisplatin, clofarabine, efavirenz/emtricitabine/tenofovir, tacrolimus... 

Frampton JE, Croom KF (2006) Efavirenz/emtricitabine/tenofovir disoproxil fumarate triple combination tablet. Drugs 66 1501-1512... 

Decks E, Perry C (2010) Efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen (Atripla ) a review of its use in the management of HIV infection. Drugs 70 2315-2338... 

Quayyum S, Dong H, Kovacic D, Sohail S, Waters B, Thornton C, et al. Combination therapy efavirenz/emtricitabine/tenofovir disoproxil fumarate associated with hepatic failure. Curr Drug Saf 2012 7(5) 391-3. 

Tenofovir in its prodrug form tenofovir, disoproxil fumarate (TDF), is indicated in the treatment of HIV infections (AIDS). It is administered as a single oral dose of 300 mg per day. When combined with emtricitabine and efavirenz, TDF has proven to be more efhcacious than the standard combination therapy of combivir (azidothymidine plus lamivudine) and efavirenz (Gallant et al. 2006) and less prone to cause adverse side effects (Pozniak et al. 2006 De Clercq 2007b). 

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

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

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. 

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. 

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... 

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. 

In 2001, tenofovir disoproxil fumarate 61, a prodrug of tenofovir was approved for treatment of HIV, subsequently being preregistered in the USA for treatment of hepatitis B. Emtricitabine 62, a reverse transcriptase inhibitor, was approved in 2003 for HIV. What is of import is that these compounds are now part of fixed dose combination therapies for treatment of HIV, either two drug (tenofovir disoproxil fumarate/emtricitabine) or three drug Atripla (tenofovir disoproxil fumarate/emtricitabine/efavirenz) formulations. Thus, even 50 + years after Bergmann s discovery of bioactive arabinose nucleosides, small molecules synthesised as result of his discoveries are still in clinical use and others are in clinical trials for treatment of viral diseases. 

Taltobulin, 11 Tamibarotene, 76 Tandutinib, 183 Tanomastat, 47 Tezacitabine, 131 Tipifamib, 172 Topixantrone, 227 Troxacitabine, 131 Vandetanib, 181 Antipsoriatic Ecalcidine, 38 Antiviral Amdoxovir, 199 Amprenavir, 4 Aplaviroc, 134 Atazanavir, 7 Capravirine, 95 Clevudine, 130 Daninavir, 5 Efavirenz, 177 Emivirine, 123 Emtricitabine, 132 Etravirine, 123 Fosamprenavir, 6 Lopinavir, 7 Maraviroc, 107 Maribavir, 158 Omaciclovir, 199 Oseltamivir, 25 Peramavir, 53 Rupinavir, 9 Tenofovir, 197 Tiprinavir, 120 Anxiolytic Sunepitron, 209 Apetite Supressant Rimonabant, 99 Cardiotonic Naxifylline, 203 Torborinone, 172 Collagenase Inhibitor Cipemastat, 99 Diuretic Lixivaptan, 222 Tolvaptan, 186 Elastase Inhibitor Sivelstat, 54... 

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. 

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... 

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. 

Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zalcitabine (production discontinued), and Zidovudine. Non-nucleoside Reverse Transcriptase Inhibitors include Delavirdine, Efavirenz, and Nevirapine. 

Musculoskeletal In ASSERT, a multicenter, open, 96-week study, 385 antiretroviral drug-naive adults with HIV infections were randomized to either abacavir -I- lamivudine or tenofovir-I-emtricitabine with efavirenz [60 ]. There was reduced bone mineral density in both groups, but to a greater extent with the latter (hip 1.9% versus 3.6% lumbar spine 1.6% versus 2.4%). Loss of at least 6% was more common in those who took tenofovir-I-emtricitabine (13% versus 3%). Markers of bone turnover (osteocalcin, procollagen 1, N-terminal propeptide, bone-specific alkaline phosphatase, and type 1 collagen cross-linked C telopep-tide) increased in both groups during the first 24 weeks and stabilized or improved thereafter, but without complete resolution. 

In a 48-week, open, randomized comparison of continuation of twice-daily zidovudine + lamivudine or replacement with once-daily tenofovir + emtricitabine in 100 individuals taking successful efavirenz-based antiretroviral therapy, limb fat mass was assessed by dual X-ray absorptiometry [70 ]. Fat was preserved or increased in the switch group but fell in the continuation group (mean difference 448 g, 95% Cl = 57, 839). The loss of limb fat was attributed to zidovudine. 

Calza L, Trapani F, Salvadori C, MagistreUi E, Manfredi R, ColangeK V, et al. Incidence of renal toxicity in HIV-infected, antiretroviral-naive patients starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir, or lopinavir/ritonavir. Scand J Infect Dis... 

Albini L, Cesana BM, Motta D, Foca E, Gotti D, Calabresi A, et al. A randomized, pilot trial to evaluate glomerular filtration rate by creatinine or cystatin C in naive HIV-infected patients after tenofovir/emtricitabine in combination with atzanavir/ritonaivir or efavirenz. J Acquir Immune Defic Syndr 2012 59(l) 18-30. 

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