Document Detail


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.
MedLine Citation:
PMID:  23412015     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jürgen K Rockstroh; Edwin DeJesus; Jeffrey L Lennox; Yazdan Yazdanpanah; Michael S Saag; Hong Wan; Anthony J Rodgers; Monica L Walker; Michael Miller; Mark J DiNubile; Bach-Yen Nguyen; Hedy Teppler; Randi Leavitt; Peter Sklar;
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Publication Detail:
Type:  Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  63     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-24     Revised Date:  2014-02-06    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  77-85     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Adenine / administration & dosage,  adverse effects,  analogs & derivatives*,  therapeutic use
Anti-HIV Agents* / administration & dosage,  adverse effects,  therapeutic use
Benzoxazines* / administration & dosage,  adverse effects,  therapeutic use
Deoxycytidine / administration & dosage,  adverse effects,  analogs & derivatives*,  therapeutic use
Double-Blind Method
Drug Combinations
Drug Therapy, Combination
Female
HIV Infections / drug therapy*,  virology
HIV-1
Humans
Male
Organophosphonates* / administration & dosage,  adverse effects,  therapeutic use
Oxazines
Pyrrolidinones* / administration & dosage,  adverse effects,  therapeutic use
Reverse Transcriptase Inhibitors* / administration & dosage,  adverse effects,  therapeutic use
Treatment Outcome
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Benzoxazines; 0/Drug Combinations; 0/Organophosphonates; 0/Oxazines; 0/Pyrrolidinones; 0/Reverse Transcriptase Inhibitors; 0/efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination; 0/emtricitabine; 0W860991D6/Deoxycytidine; 107021-12-5/tenofovir; 22VKV8053U/raltegravir; JAC85A2161/Adenine; JE6H2O27P8/efavirenz
Investigator
Investigator/Affiliation:
D Cooper / ; J Madruga / ; E Netto / ; R Zajdenverg / ; J G Baril / ; C Kovacs / ; F Smaill / ; A Afani / ; C Beltran / ; J Perez Godoy / ; M Angela / ; A Arango / ; J Tamara / ; J Velez / ; L Cotte / ; P -M Girard / ; G Pialoux / ; D Salmon-Ceron / ; Y Yazdanpanah / ; S Esser / ; G Fatkenheuer / ; J K Rockstroh / ; R Schmidt / ; H -J Stellbrink / ; M Dinaker / ; A Pazare / ; J Rajendran / ; O Srivastava / ; G Carosi / ; A Castagna / ; A Chirianni / ; R Esposito / ; A Lazzarin / ; C Viscoli / ; J Andrade / ; N Quintero Perez / ; G Reyes / ; J Sierra / ; I Torres / ; E Gotuzzo / ; J Lama / ; R Cabello-Chavez / ; R Salazar / ; J Portilla Sogorb / ; A Rivero-Roman / ; J Santamaria Jauregui / ; W Manosuthi / ; S Sungkanuparph / ; K Supparatpinyo / ; A Vibhagool / ; D Berger / ; E DeJesus / ; T Friel / ; C Hicks / ; M Kozal / ; P Kumar / ; J L Lennox / ; R Liporace / ; S Little / ; J Morales-Ramirez / ; R Novak / ; R Pollard / ; M Saag / ; S Santiago / ; S Schneider / ; R Steigbigel / ; W Towner / ; D Wright /

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