2011•AIDSOpen access
Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262)
Babafemi Taiwo, Lu Zheng, Sébastien Gallien, Roy M. Matining, Daniel R. Kuritzkes, Cara C. Wilson, Baiba Berzins, Edward P. Acosta, Barbara Bastow, Peter S. Kim, Joseph J. Eron
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Abstract
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/μl 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.