This fixed-dose tablet combines 600mg efavirenz, 200mg emtricitabine (FTC), and 245mg tenofovir disoproxil fumarate (TDF).
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI), and tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor (NtRTI). These drugs reduce the amount of HIV in the body and prevent the development of AIDS-defining illnesses.
The fixed-dose combination was first approved as Atripla in the United States in 2006 and in the European Union in late 2007. Numerous generic versions are also available. Branded Atripla will be discontinued at the end of 2021 due to lack of demand.
In the European Union and United Kingdom efavirenz/tenofovir (TDF)/emtricitabine is licensed for use in patients who have already achieved undetectable viral load on a combination in which the components are dosed separately as tenofovir (TDF)/emtricitabine and efavirenz. In the United States it can be used as initial therapy without the need for an induction phase using separate components. The European medicines licensing body has not issued an explanation of its divergent licensing decision.
Atripla was licensed on the basis of data from Study 934, which compared efavirenz (Sustiva), emtricitabine (Emtriva) and tenofovir disoproxil fumarate (Viread) taken as separate drugs, to the combination of efavirenz and zidovudine (AZT) plus lamivudine (3TC) as Combivir. In this study, more patients in the emtricitabine and tenofovir arm achieved viral loads below 400 copies/ml after 48 weeks, largely due to fewer discontinuations due to drug side effects. (Gallant) A study in HIV-negative subjects revealed that the triple combination tablet produces blood levels equivalent to the three drugs taken separately.
The standard dose of the efavirenz/tenofovir (TDF)/emtricitabine fixed-dose tablet is one tablet once a day. The manufacturers advise patients to take the tablet on an empty stomach before going to bed.
The most common side effects of the efavirenz/tenofovir (TDF)/emtricitabine fixed-dose tablet are rash, dizziness, headache, depression, anxiety, abnormal dreams, difficulty in sleeping, concentration problems, drowsiness, diarrhoea, nausea, vomiting, abdominal pain, itching, fatigue and weakness.
Increases in lipid levels, liver enzymes, pancreatic enzymes, blood glucose, phosphate and creatine kinase are common in people taking this combination.
The combination should not be taken by people with impaired kidney function (creatine clearance less than 50ml/min).
Because of the efavirenz component in this fixed-dose combination, use of many drugs is contraindicated or may require dosing adjustment. See efavirenz for further details.
Viral rebound or lack of viral suppression on the efavirenz/tenofovir (TDF)/emtricitabine combination most frequently leads to resistance to efavirenz and cross-resistance to other non-nucleoside reverse transcriptase inhibitors. Emtricitabine and TDF resistance were rare in people experiencing viral rebound on this combination in Study 934.
See efavirenz for further details.
The efavirenz/tenofovir (TDF)/emtricitabine combination tablet is not approved for use in children or adolescents under 18 years of age.
Gallant JE et al. Tenofovir DF, Emtricitabine, and Efavirenz vs. Zidovudine, Lamivudine, and Efavirenz for HIV. New England Journal of Medicine, 354:251-260, 2006.