Background: Sparing NRTI therapy can be a real option in case of severe adverse events or extensive NRTI resistance. PIs plus NNRTIs may be used, although their efficacy and safety have been no extensively assessed. The efficacy of SQV-sgc + RTV (1600/100 mg) once-daily is currently being evaluated with encouraging results. Although the combination of SQV and EFV is disapproved, adding RTV might reverse the effect EFV has on the induction of SQV metabolism. The objective was to evaluate the pharmacokinetics (PK), safety, and efficacy of a qd sparing-NRTI HAART (SQV-sgc + RTV [1200/100 mg] + EFV600 mg) in HIV-pretreated patients in whom NRTIs were withdrawn because of adverse events.

Methods: This was an open-label, prospective study in which 42 HIV-1-infected patients were included without entry restrictions on plasma HIV-1 RNA (VL), CD4 cell count, or previous antiretroviral treatment. The PK study was carried out in 32 unselected patients (24 hour profile: 19; trough level: 13). Plasma SQV and EFV were measured by validated HPLC methods and a non-compartmental analysis was done. Efficacy was analyzed by intention-to-treat (ITT). Virologic failure was defined as a corroborated VL >50 copies RNA/mL or premature treatment discontinuation due to whatever reason. Results are expressed as median (range).

Results: At inclusion, VL was <50 copies/mL in 22 patients with a CD4 cell count of 625/µL (121-1004/µL), and 2700 copies/mL (146-696,000/µL ) and 443/µL (134-1133/µL), respectively, in other 20 patients. All patients were NRTI and PIs experienced with a median of 54 and 30 months of prior therapy, respectively, and previous virologic failures with ³1 PIs in 22 cases. Furthermore, 28 patients were NNRTI experienced and 7 of them had a detectable VL when treatment was switched to this regimen. The median follow-up was 12 months (1-18 months).  SQV: Cmax (n= 19): 2360 ng/mL (699- 6395 ng/mL), AUC_0-24 (n= 19): 16230 ng·h/mL (6704-49454 ng·h/mL), Cmin (n=32): 144 ng/mL (70 – 984 ng/mL). EFV: Cmax (n= 19): 6.4 mg/mL (1.7 – 8.9 mg/mL), AUC_0-24 (n= 19): 88.9 mg·h/mL (17-161.9 mg·h/mL), Cmin (n=32): 2.8 mg/mL (0.5- 6.3 mg/mL).  All 22 patients entering the study with <50 copies/mL remained stable, and 13/20 patients with a high viral load became undetectable with no further increases during their follow up. 5 patients dropped out, even though maintaining an undetectable VL after 1-9 months. By ITT, VL was <50 copies/mL in 71% at 52 weeks and the median CD4 cell count increase was 215 cells/mm³.  Treatment had to be withdrawn in only 1 case (hepatitis in a patient with chronic hepatitis by B and C virus). Basal total cholesterol and triglycerides were 208 mg/dL and 169 mg/dL, and 221 mg/dL and 261 mg/dL at 52 weeks, respectively.

Conclusions: The pharmacokinetic, efficacy, and tolerance data of SQV-sgc + RTV (1200/100 mg) + EFV 600 mg and a qd administration shape up this combination as a good option as a sparing NRTI regimen.