Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen: A Review of Its Use in HIV Infection

Abstract

The nucleos(t)ide reverse transcriptase inhibitors, emtricitabine and tenofovir disoproxil fumarate (tenofovir DF), and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, are now available as a fixed-dose single-tablet regimen (emtricitabine/rilpivirine/tenofovir DF; Complera(®), Eviplera(®)) for the treatment of adults infected with HIV-1. In treatment-naïve adults, once-daily emtricitabine/rilpivirine/tenofovir DF was noninferior to once-daily emtricitabine/efavirenz/tenofovir DF with regard to establishing virological suppression over 96 weeks of therapy in a randomized, open-label, phase IIIb study (STaR). These data confirmed the findings of a pooled subset analysis of two earlier 96-week, double-blind, phase III trials (ECHO and THRIVE) in which treatment-naïve adults received either rilpivirine or efavirenz in combination with emtricitabine/tenofovir DF. However, the virological benefit of emtricitabine/rilpivirine/tenofovir DF in this setting appeared limited in patients with low CD4+ cell counts or high viral loads at baseline. In 48-week phase IIIb (SPIRIT) and IIb (Study 111) trials in treatment-experienced patients already virologically suppressed with a single- or multiple-tablet antiretroviral regimen and without prior virological failure, switching to once-daily emtricitabine/rilpivirine/tenofovir DF maintained virological suppression and was noninferior to remaining on a more complex multiple-tablet regimen in this regard. Emtricitabine/rilpivirine/tenofovir DF is generally well tolerated and appears to have a more favourable tolerability profile than emtricitabine/efavirenz/tenofovir DF. Thus, emtricitabine/rilpivirine/tenofovir DF is a welcome addition to the other single-tablet regimens currently available for the treatment of HIV-1 infection, providing a convenient and effective option for some adults who are treatment-naïve, as well as those who are already virologically suppressed on their current treatment regimen and wish to switch because of intolerance or to simplify their regimen.

Simultaneous determination and validation of emtricitabine, rilpivirine and tenofovir from biological samples using LC and CE methods

“…A combined formulation of these antiretroviral drugs is used in the treatment of naive and virologically suppressed patients who have an HIV‐1 RNA plasma viral load of ≤100,000 copies/mL (Amiel et al, ). Emtricitabine (EMT) {5‐fluoro‐1‐(2 R ,5 S )‐[(2‐hydroxy‐methyl)‐1,3‐oxathiolan‐5‐yl] cytosine} and tenofovir disproxil fumarate (TEN) (9‐{( R )‐2‐[( bis {[(isopropoxycarbonyl)oxy]methoxy} phosphinyl)methoxy]propyl} adenine fumarate) are nucleoside reverse transcriptase inhibitors (Deeks, ), while rilpivirine (RIL) (4‐{[4‐({4‐[( E )‐2‐cyanovinyl]‐2,6‐dimethylphenyl}amino)pyrimidin‐2‐yl]amino}benzonitrile) is a non‐nucleoside reverse transcriptase inhibitor (Amiel et al, ). This study describes the separation of these binary mixtures from the urine matrix.…”

Selective Optimization of Side Activities (SOSA) in Drug Discovery

“…Likewise, this approach has also found to be useful in treating patients infected with the hepatitis C virus (HCV) [3]. Examples of this are Atripla s (used in HIV treatment), which combines an NNRTI and two NRTIs in a single tablet, and Vytorin s (used to treat hypercholesterolemia), which is a combination of the cholesterol absorption inhibitor ezetimibe and the statin simvastatin [4,5]. Examples of this are Atripla s (used in HIV treatment), which combines an NNRTI and two NRTIs in a single tablet, and Vytorin s (used to treat hypercholesterolemia), which is a combination of the cholesterol absorption inhibitor ezetimibe and the statin simvastatin [4,5].…”