A Randomized, Double-Blind Comparison of Coformulated Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF vs Ritonavir-Boosted Atazanavir Plus Coformulated Emtricitabine and Tenofovir DF for Initial Treatment of HIV-1 Infection: Analysis of Week 96 Results

1Department of Medicine I, University of Bonn, Bonn, Germany 2Orlando Immunology Center, Orlando, FL, USA 3Hennepin County Medical Center, Minneapolis, MN, USA 4Hopital Saint-Louis, AP-HP and University of Paris Sorbonne Cité, INSERM U941, France 5Therapeutic Concepts, Houston, TX, USA 6Gilead Sciences, Foster City, CA, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 01/2013; 62(5). DOI: 10.1097/QAI.0b013e318286415c
Source: PubMed

ABSTRACT This ongoing, randomized, double-blind, active-controlled Phase 3 international trial demonstrated the non-inferior efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF) compared to atazanavir boosted by ritonavir (ATV/RTV) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) at 48 weeks. Here, we report the Week 96 results. Of 708 treated subjects, virologic success (FDA Snapshot) was maintained at Week 96 with EVG/COBI/FTC/TDF and ATV/RTV+FTC/TDF (83% vs 82%, difference 1.1%, 95% CI -4.5% to 6.7%). Study drug discontinuations due to adverse events (AEs) were low (4% vs 6%). Median increases from baseline in serum Cr (mg/dL) in EVG/COBI/FTC/TDF vs ATV/RTV+FTC/TDF at Week 96 (0.12 vs 0.08) were similar to those at Week 48 (0.12 vs 0.08). EVG/COBI/FTC/TDF showed similar mean decreases (%) in BMD from baseline vs ATV/RTV+FTC/TDF (hip: -3.16 vs -4.19, P= 0.069, spine: -1.96 vs -3.54, P=0.049). Overall, Week 96 results support durable efficacy and safety of EVG/COBI/FTC/TDF in HIV-1 infected patients.

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Available from: Michael E Abram, Dec 04, 2014
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    ABSTRACT: We report Week 96 results from a phase 3 trial of elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF, n=348) vs efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF, n=352). At Week 48, EVG/COBI/FTC/TDF was non-inferior to EFV/FTC/TDF (88% vs 84%, difference +3.6%, 95% CI -1.6% to 8.8%). Virologic success (HIV-1 RNA <50 copies/mL) was maintained at Week 96 (84% vs 82%, difference +2.7%, 95% CI -2.9% to 8.3%). Discontinuation due to adverse events was low (5% vs 7%). Median changes in serum creatinine (mg/dL) at Week 96 were similar to Week 48. These results support the durable efficacy and long-term safety of EVG/COBI/FTC/TDF.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2013; 65(3). DOI:10.1097/QAI.0b013e318289545c · 4.39 Impact Factor
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    ABSTRACT: Introduction: The number of HIV patients receiving antiretroviral therapy is increasing worldwide, as new infections continue to occur and access to drugs is scaling up in most developing regions. Due to the efficacious nature of combination antiretroviral therapy in most drug-adherent patients, the concerns on the safety profile of these lifelong medicines have attracted great attention. Areas covered: Side effects of antiretroviral agents can be clinically symptomatic or manifest only as laboratory abnormalities. Drug-related toxicities can be grouped by antiretroviral drug class or damage of distinct body organs/systems. By mechanism, antiretroviral-associated adverse events generally result from hypersensitivity reactions, direct cytopathic effect, or idiosyncratic phenomena. Expert opinion: A good knowledge of the toxicity profile of antiretroviral agents is warranted for HIV care providers in order to prevent and avoid unwanted complications.
    Expert Opinion on Drug Safety 06/2013; 12(5). DOI:10.1517/14740338.2013.806480 · 2.74 Impact Factor
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    ABSTRACT: Once-daily single-tablet antiretroviral regimen containing tenofovir (TFV) disoproxil fumurate, emtricitabine, elvitegravir and cobicistat (COBI) is an approved combination for the treatment of patients infected with HIV. COBI and TFV have been reported to interact with distinct transporters in renal proximal tubules; while TFV is renally eliminated by a combination of glomerular filtration and tubular secretion via anion transporters OAT1, OAT3 and MRP4, COBI inhibits renal cation transporters, particularly MATE1, resulting in a measurable decrease in the tubular secretion of creatinine. To investigate the potential for a renal drug-drug interaction between TFV and COBI in vitro, the uptake of TFV in the presence and absence of COBI was determined in fresh human renal cortex tissue and in cells expressing the relevant renal transporters. At concentrations exceeding clinical protein-unbound plasma levels, COBI did not significantly inhibit the transport of TFV by the anion transporters OAT1, OAT3 or MRP4 (IC50 values of >15, 6.6 and 8.5 μM, respectively). Conversely, TFV had little or no effect on the cation transporters OCT2 and MATE1 (IC50 > 100 μM). Consistent with studies using individual transporters, no increase in the accumulation of TFV in freshly isolated human renal cortex tissue or renal proximal tubule cells (RPTECs) was observed in the presence of COBI. Finally, COBI alone or in combination with FTC and EVG did not affect the sensitivity to TFV of cultured primary RPTECs or cells co-expressing OAT1 and MRP4. These results illustrate that COBI and TFV interact primarily with distinct renal transporters and indicate a low potential for pharmacokinetic renal drug-drug interaction.
    Antimicrobial Agents and Chemotherapy 07/2013; DOI:10.1128/AAC.00712-13 · 4.45 Impact Factor