title: Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK.
abstract: BACKGROUND
  STARTMRK, a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients, remained blinded until its conclusion at 5 years. We now report the final study results.
  
  
  METHODS
  Previously untreated patients without baseline resistance to efavirenz, tenofovir, or emtricitabine were eligible for a randomized study of tenofovir/emtricitabine plus either raltegravir or efavirenz. Yearly analyses were planned, with primary and secondary end points stipulated at weeks 48 and 96, respectively. The primary efficacy outcome was the percentage of patients with viral RNA (vRNA) levels <50 copies per milliliter counting noncompleters as failures (NC=F). Changes from baseline CD4 count were computed using an observed-failure approach to missing data. No formal hypotheses were formulated for testing at week 240.
  
  
  RESULTS
  Overall, 71 of 281 raltegravir recipients (25%) and 98 of 282 efavirenz recipients (35%) discontinued the study; discontinuations due to adverse events occurred in 14 (5%) and 28 (10%) patients in the respective groups. In the primary NC=F efficacy analysis at week 240, 198 of 279 (71.0%) raltegravir recipients and 171 of 279 (61.3%) efavirenz recipients had vRNA levels <50 copies per milliliter, yielding a treatment difference {Δ [95% confidence interval (CI)] = 9.5 (1.7 to 17.3)}. Generally comparable between-treatment differences were seen in both the protocol-stipulated sensitivity analyses and the prespecified subgroup analyses. The mean (95% CI) increments in baseline CD4 counts at week 240 were 374 and 312 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Δ(95% CI) = 62 (22 to 102)]. Overall, significantly fewer raltegravir than efavirenz recipients experienced neuropsychiatric side effects (39.1% vs 64.2%, P < 0.001) or drug-related clinical adverse events (52.0% vs 80.1%, P < 0.001).
  
  
  CONCLUSIONS
  In this exploratory analysis of combination therapy with tenofovir/emtricitabine in treatment-naive patients at week 240, vRNA suppression rates and increases in baseline CD4 counts were significantly higher in raltegravir than efavirenz recipients. Over the entire study, fewer patients experienced neuropsychiatric and drug-related adverse events in the raltegravir group than in the efavirenz group. Based on better virologic and immunologic outcomes after 240 weeks, raltegravir/tenofovir/emtricitabine seemed to have superior efficacy compared with efavirenz/tenofovir/emtricitabine.
authors: Department of Medicine I, University of Bonn, Bonn, Germany.
authors: Jürgen K
authors: JK
authors: Rockstroh
authors: Edwin
authors: E
authors: DeJesus
authors: Jeffrey L
authors: JL
authors: Lennox
authors: Yazdan
authors: Y
authors: Yazdanpanah
authors: Michael S
authors: MS
authors: Saag
authors: Hong
authors: H
authors: Wan
authors: Anthony J
authors: AJ
authors: Rodgers
authors: Monica L
authors: ML
authors: Walker
authors: Michael
authors: M
authors: Miller
authors: Mark J
authors: MJ
authors: DiNubile
authors: Bach-Yen
authors: BY
authors: Nguyen
authors: Hedy
authors: H
authors: Teppler
authors: Randi
authors: R
authors: Leavitt
authors: Peter
authors: P
authors: Sklar
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000068257:Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010078:Oxazines; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D000068257:Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D063065:Organophosphonates; D010078:Oxazines; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz