Elvitegravir is a novel HIV integrase strand transfer inhibitor with potent antiviral activity. It is combined with cobicistat, a cytochrome P450 3A inhibitor that has no anti-HIV activity but acts as a pharmacoenhancer allowing once-daily dosing. The remaining components, emtricitabine and tenofovir disoproxil, are established nucleoside/nucleotide reverse transcriptase inhibitors.1
The safety and efficacy of a single-tablet regimen comprising elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil were assessed in two randomised, active-controlled phase III studies involving 1,408 antiretroviral-naive HIV-infected patients.1-3
Patients eligible for inclusion had plasma HIV-1 RNA concentrations of ≥5,000 copies per ml, an estimated glomerular filtration rate of ≥70ml/min and were susceptible to emtricitabine, tenofovir and efavirenz/atazanavir by HIV-1 genotype.2,3
The four-drug, single-tablet regimen was compared with a once-daily fixed-dose combination of efavirenz/emtricitabine/tenofovir disoproxil (Atripla®) in study 102 (n=700) and with ritonavir-boosted atazanavir plus a fixed dose combination of emtricitabine/tenofovir disoproxil (Truvada®) in study 103 (n=708).2,3
The four-drug regimen was found to be non-inferior to the comparator regimen in both studies in terms of virologic response at 48 weeks, the primary outcome measure (defined as <50 HIV-1 RNA copies/ml).1-3
Virologic success was achieved in 88% and 90% of patients receiving the four-drug single-tablet regimen in studies 102 and 103, respectively, compared with 84% of those receiving the efavirenz/emtricitabine/tenofovir disoproxil regimen and 87% of those receiving ritonavir/atazanavir plus emtricitabine/tenofovir disoproxil.1-3
Safety and tolerability of the four-drug single-tablet regimen was similar to that of the two comparator regimens, with nausea and diarrhoea the most commonly reported adverse effects.1-3
- Stribild Summary of Product Characteristics, May 2013.
- Sax PE et al. Lancet 2012; 379: 2439–48.
- DeJesus E et al. Lancet 2012; 379: 2429–38.
Further information: Gilead