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Background:  Our objective was to evaluate the efficacy and tolerability of dual boosted protease inhibitor (PI) regimens in HIV-1-infected patients with resistance mutations or intolerance to reverse transcriptase inhibitors (RTI).

Methods:  In a prospective open-label study, treatment-experienced patients, either resistant (Gp1) or intolerant to RTI (Gp2), were started on a dual boosted PI regimen without RTI. Viral load and CD4 count were performed at week 4 and then every 3 months. A genotypic resistance test was assessed at baseline and PI trough concentrations (C_min) were measured at week 4. The primary endpoint was the percentage of patients with a viral load < 400 copies/mL at week 24 according to both intent-to-treat and on-treatment analysis.

Results:  We enrolled 82 patients (41 patients per group) whose baseline median viral load was 12,700 copies/mL (range 304 to 750,000) and CD4 count was 240/mm³ (range 36 to 548) in Gp1 and 294/mm³ (range 27 to 1012) with a viral load of < 400 copies/mL in 71% of patients in Gp2 (12 patients in Gp2 were in treatment interruption before inclusion). Median number of prior PI exposure was 2 in both groups. Ten patients in Gp1 and 7 pts Gp2 were PI naive. A genotypic resistance test performed in 44 of 53 patients showed at least 1 PI primary resistance mutation in 32% patients. All PI combinations they received were adequate with a genotypic resistance test. Most frequent regimens were saquinavir (SQV) 800 mg/lopinavir (LPV) 400 mg/ritonavir (RTV) 100 mg twice daily (40%), indinavir (IDV) 400 mg/LPV 400 mg/RTV 100 mg twice daily (30%) and IDV 400 mg/amprenavir (APV) 600 mg/RTV 100 mg twice daily (17%). Two patients were lost to follow-up and 1 died. In Gp2, 78% of patients (28 of 41) sustained a viral load of < 400 copies/mL between baseline and week 24. Overall at week 24, 82% (67of 82 patients) and 93% (67 of 72 patients) had a viral load of < 400 copies/mL by intent-to-treat and on-treatment analysis, respectively. Seven patients discontinued study regimen before week 24 (Gp1= 5 and Gp2 = 2) and 5 patients experienced virologic failure at week 24 (Gp1 = 4; Gp2 = 1). Median C_min were adequate at week 4 in the 3 regimens (SQV 408 ng/mL, LPV 4494 ng/mL, RTV 188 ng/mL; IDV 251 ng/mL, LPV 6194 ng/mL, RTV 221 ng/mL; IDV 375 ng/mL, APV 1872 ng/mL, RTV 287 ng/mL). Respectively, 76% (25 of 33 patients), 84% (21 of 25 patients), and 93% (13 of 14 patients) of patients on SQV/LPV/RTV, IDV/LPV/RTV, and IDV/APV/RTV had undetectable viral load. Mainly because of gastrointestinal intolerance with sustained virologic success, 20 patients switched to another dual PI regimen.

Conclusions:  An exclusive dual boosted PI regimen is an effective and safe antiretroviral therapy, particularly in patients with no options between the 2 remaining RT inhibitors classes.

Keywords: Antiretroviral therapy; Protease Inhibitors; resistance