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.