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: 4.56). 01/2013; 62(5). DOI: 10.1097/QAI.0b013e318286415c
Source: PubMed


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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    • "In the open-label STaR study, the TDF/FTC/RPV STR favorably compared with the TDF/FTC/EFV STR. Considering the totality of patients the second-generation STR was non-inferior to the control arm and a post hoc analysis stratified according to the baseline viral load, revealed that TDF/FTC/RPV was superior to TDF/FTC/EFV in patients with viral load <100,000 copies/mL [49]. "
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    ABSTRACT: Combined antiretroviral therapy (cART) has evolved considerably over the past decades leading to a better control of human immunodeficiency virus replication. Recently, regimens have evolved so as to simplify dosing frequency and reduce pill burden to improve adherence. Several national and international guidelines suggest antiretroviral (ARV) regimen simplification as a method of improving adherence. Decreased cART adherence has been associated with both patient-related factors and regimen-related factors. Adherence rates are statistically higher when simpler, once-daily (OD) regimens are combined with smaller daily regimen pill burdens. The avoidance of selective non-adherence, where a patient takes part of a regimen but not the full regimen, is a further potential benefit offered by single-tablet regimens (STRs). Simplification of cART has been associated with a better quality of life (QoL). Although tempered by other factors, better adherence, higher QoL and patients’ preferences are all key points which might combine to assure long-lasting efficacy and durability of cART. All studies underlined the favorable tolerability profile of newer STRs. Three STRs are currently available. Tenofovir (TDF) plus emtricitabine (FTC)/efavirenz (EFV) was the first OD complete ARV regimen available as a STR. TDF plus FTC/rilpivirine is a second-generation STR. The most recently approved STR, TDF plus FTC/cobicistat/elvitegravir, is the first non-nucleoside reverse transcriptase inhibitor-based STR. All of them have shown excellent efficacy; safety and tolerability have been improved by more recent formulations. Several other STRs are anticipated both combining completely different drugs, abacavir (ABC) plus lamivudine (3TC)/dolutegravir, utilizing innovative formulations of older drugs, tenofovir alafenamide fumarate, or taking advance of bioequivalent drugs, lamivudine (3TC) plus ABC/EFV. The future challenge would be to develop completely alternative STRs (including for example protease inhibitors or new molecules) to extend the advantages of simplicity to heavily pre-treated individuals. Electronic supplementary material The online version of this article (doi:10.1007/s40121-014-0024-z) contains supplementary material, which is available to authorized users.
    02/2014; 3(1). DOI:10.1007/s40121-014-0024-z
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    • "Both RAL [24, 28–32] and cobicistat (c)-boosted EVG [33, 34] have demonstrated non-inferiority to efavirenz (EFV) when co-administered in combination with tenofovir (TDF)/emtricitabine (FTC). EVG/c is also non-inferior to ATV/r when combined with TDF/FTC [35, 36]. Non-inferiority was also demonstrated for DTG compared to EFV in the SPRING-1 (A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects) study in which patients were randomized to receive either TDF/FTC or abacavir (ABC)/lamivudine (3TC) [37, 38]. "
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    ABSTRACT: HIV drug resistance has been one of the major obstacles to HIV eradication and has contributed to the need for the constant development of new antiretroviral drugs over the past 25 years. With the recent approval of dolutegravir for human therapy by the U.S. Food and Drug Administration, health practitioners may soon have access to three integrase strand transfer inhibitors to treat individuals living with HIV. Here, we review the use of raltegravir, elvitegravir, and dolutegravir for use in first- and second-line HIV treatment regimens and the issue of HIV resistance against integrase inhibitors. Electronic supplementary material The online version of this article (doi:10.1007/s40121-013-0020-8) contains supplementary material, which is available to authorized users.
    12/2013; 2(2):83-93. DOI:10.1007/s40121-013-0020-8
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    • "Further two patients (0.6%) in the Stribild arm discontinued study drug between weeks 48 and 96, because of renal adverse events consisting of serum creatinine elevations not accompanied by proximal tubulopathy [31]. In the 0103 study, five patients (Stribild arm 3, ATV/RTV arm 2) discontinued study drug due to renal events before week 96; none had evidence of proximal tubulopathy [32]. In the 0114 study, 1.7% and 1.4% of patients discontinued study medication for renal events in the COBI and RTV arms, and 5 vs. 2 cases had proximal tubulopathy [33]. "
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    ABSTRACT: Human immunodeficiency virus (HIV) therapy has evolved over the last 20 years from mono-drug therapy given five times daily to regimens consisting of three or four drugs combined in a single-tablet dosed once daily. To allow once-daily administration, several drugs require pharmacokinetic boosting by a concomitantly administered P-glycoprotein and cytochrome P450 inhibitor such as ritonavir. The availability of cobicistat provides an alternative to ritonavir to those who are intolerant to this drug, and the opportunity for co-formulated single-tablet regimens consisting of tenofovir/emtricitabine, cobicistat and elvitegravir, atazanavir or darunavir. The cobicistat/elvitegravir-based regimen is well tolerated and patients achieved high rates of HIV RNA suppression in clinical trials. Cobicistat inhibits renal tubular secretion of creatinine, resulting in increased serum creatinine concentrations and reduced estimated glomerular filtration rate, with a new set point reached after 4 weeks. Treatment limiting renal toxicity with cobicistat/elvitegravir and tenofovir disoproxil fumarate is infrequent and may be further reduced when cobicistat is co-formulated with tenofovir alafenamide fumarate, a novel formation of tenofovir currently undergoing clinical trials.
    12/2013; 2(2):111-22. DOI:10.1007/s40121-013-0013-7
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