期刊
AIDS
卷 25, 期 17, 页码 2113-2122出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e32834bbaa9
关键词
antiretroviral therapy; darunavir; nucleoside sparing; raltegravir
资金
- National Institute of Allergy and Infectious Diseases [U01AI068636, U01AI68634]
- National Institute of Mental Health (NIMH)
- National Institute of Dental and Craniofacial Research (NIDCR)
- National Center for Research Resources
- Tibotec
- GlaxoSmithKline
- Merck
- Northwestern University [AI069471]
- University of California San Diego [AI 69432]
- Ohio State University [AI069474]
- MetroHealth Medical Center [AI-069501]
- Alabama Therapeutics CRS [U01 AI069452]
- University of Pennsylvania [U01-AI-69467-05, P30-AI-045008-12]
- UCSF AIDS CRS [5UO1 AI069502]
- Washington University in St. Louis [AI 069495]
- Duke University Medical Center CRS [5U01 AI069484]
- University of Cincinnati [1U01AI069513]
- UNC AIDS Clinical Trials Unit UNC AIDS CRS [5-U01 AI069423, UL 1RR 025747, AI50410]
- Houston AIDS Research (HART) [1U01AI069503]
- Beth Israel Deaconess (Partners/Harvard) CRS [U01 AI069472-05]
- Stanford University AIDS CTU [AI069556]
- Georgetown University [5U01AI069494]
- AIDS Care [U01AI069511-02, UL1 RR 024160]
- Vanderbilt Therapeutics CRS [AI-069439, RR-024975]
- Pittsburgh CRS [1 UO1 AI 069494-01]
- Case CRS [AI69501]
Objective: To explore darunavir/ritonavir (DRV/r) plus raltegravir (RAL) combination therapy in antiretroviral-naive patients. Design: Phase IIb, single-arm, open-label, multicenter study. Methods: One hundred and twelve antiretroviral-naive, HIV-1-infected patients received DRV/r 800/100 mg once daily and RAL 400 mg twice daily. Primary endpoint was virologic failure by week 24. Virologic failure was defined as confirmed viral load of 1000 copies/ml or more at week 12, or an increase of more than 0.5 log(10) copies/ml in viral load from week 4 to 12, or a confirmed viral load of more than 50 copies/ml at or after week 24. Protease and integrase genes were sequenced in patients experiencing virologic failure. Results: Virologic failure rate was 16% [95% confidence interval (CI) 10-24] by week 24 and 26% (95% CI 19-36) by week 48 in an intent-to-treat analysis. Viral load at virologic failure was 51-200 copies/ml in 17/28 failures. Adjusting for age and sex, virologic failure was associated with baseline viral load of more than 100 000 copies/ml [hazard ratio 3.76, 95% CI (1.52-9.31), P = 0.004] and lower CD4 cell count [0.77 per 100 cells/mu l increase (95% CI 0.61-0.98), P - 0.037]. When trough RAL concentrations were included as a time-varying covariate in the analysis, virologic failure remained associated with baseline viral load more than 100 000 copies/ml [hazard ratio = 4.67 (95% CI 1.93-11.25), P < 0.001], whereas RAL level below detection limit in plasma at one or more previous visits was associated with increased hazard [hazard ratio = 3.42 (95% CI 1.41-8.26), P = 0.006]. All five participants with integrase mutations during virologic failure had baseline viral load more than 100 000 copies/ml. Conclusion: DRV/r plus RAL was effective and well tolerated in most patients, but virologic failure and integrase resistance were common, particularly in patients with baseline viral load more than 100 000 copies/ml. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
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