title: Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial.
abstract: BACKGROUND
  Patients with HIV on antiretroviral therapy might benefit from regimen simplification to reduce pill burden and dosing frequency. We aimed to assess the safety and efficacy of simplifying the treatment regimen for adults with virologically suppressed HIV infection from a ritonavir-boosted protease inhibitor and emtricitabine plus tenofovir disoproxil fumarate (tenofovir) regimen to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir.
  
  
  METHODS
  STRATEGY-PI is a 96 week, international, multicentre, randomised, open-label, phase 3b trial in which HIV-infected adults with a plasma HIV-1 RNA viral load of less than 50 copies per mL for at least 6 months who were taking a ritonavir-boosted protease inhibitor with emtricitabine plus tenofovir were randomly assigned (2:1) either to switch to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir or to continue on their existing regimen. Key eligibility criteria included no history of virological failure, no resistance to emtricitabine and tenofovir, and creatinine clearance of 70 mL/min or higher. Neither participants nor investigators were masked to group allocation. The primary endpoint was the proportion of participants with a viral load of less than 50 copies per mL at week 48, based on a US Food and Drug Administration snapshot algorithm for the modified intention-to-treat population, which excluded major protocol violations (prohibited resistance or not receiving a protease inhibitor at baseline). We prespecified non-inferiority with a 12% margin; if non-inferiority was established, superiority was tested as per a prespecified sequential testing procedure. This trial is registered at ClinicalTrials.gov, number NCT01475838.
  
  
  RESULTS
  Between Dec 12, 2011, and Dec 20, 2012, 433 participants were randomly assigned and received at least one dose of study drug. Of these participants, 293 were assigned to switch to the simplified regimen (switch group) and 140 to remain on their existing regimen (no-switch group); after exclusions, 290 and 139 participants, respectively, were analysed in the modified intention-to-treat population. At week 48, 272 (93·8%) of 290 participants in the switch group maintained a viral load of less than 50 copies per mL, compared with 121 (87·1%) of 139 in the no-switch group (difference 6·7%, 95% CI 0·4-13·7; p=0·025). The statistical superiority of the simplified regimen was mainly caused by a higher proportion of participants in the no-switch group than in the switch group discontinuing treatment for non-virological reasons; virological failure was rare in both groups (two [1%] of 290 vs two [1%] of 139). We did not detect any treatment-emergent resistance in either group. Adverse events leading to discontinuation were rare in both groups (six [2%] of 293 vs four [3%] of 140). Switching to the simplified regimen was associated with a small, non-progressive increase from baseline in serum creatinine concentration. Nausea was more common in the switch group than in the no-switch group, but rates of diarrhoea and bloating decreased compared with baseline from week 4 to week 48 in the switch group, whereas there were generally no changes for these symptoms in the no-switch group.
  
  
  CONCLUSIONS
  Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir might be a useful regimen simplification option for virologically supressed adults with HIV taking a multitablet ritonavir-boosted protease inhibitor regimen.
  
  
  BACKGROUND
  Gilead Sciences.
authors.affiliation: HIV Unit, Internal Medicine, Hospital La Paz, IdiPAZ, Madrid, Spain. Electronic address: joser.arribas@salud.madrid.org.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Arribas
authors.affiliation: Infectious Diseases, Pierre and Marie Curie University, Hôpital Tenon, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.affiliation: Infectious Diseases, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gathe
authors.affiliation: Medical Sciences, University of Turin School of Medicine, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Infectious Diseases, Centre Hospitalier Universitaire Gui de Chauliac, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.affiliation: Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Thai
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Ramin
authors.initials: R
authors.lastname: Ebrahimi
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: White
authors.affiliation: Gilead Sciences, Foster City, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Piontkowsky
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D000069547:Cobicistat; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D000068679:Emtricitabine; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D063065:Organophosphonates; D011480:Protease Inhibitors; D015363:Quinolones; D013844:Thiazoles; D003841:Deoxycytidine; C509700:elvitegravir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069547:Cobicistat; D019438:Ritonavir