Background: To evaluate the benefit of plasmatic drug measurements (PDM) in association with genotypic resistance testing to optimize therapy in patients failing antiretroviral treatments.

Methods: An open, prospective, randomized, single center study in patients failing ART. Patients with HIV-1 RNA>1000 copies/mL and stable ART in the last 3 months were randomized in 2 groups: genotypic group (G) and geno-pharmacologic group (GP). Patients were evaluated monthly clinically, for safety parameters, for HIV-1 RNA, for CD4 cell counts, and for PI and/or NNRTI peak and trough plasma levels until week 24. ART was selected by an expert committee according to genotypic resistance testing (groups G and GP) and PDM (group GP) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and PDM. At week 12, results of PDM were available for group G. Primary  end-point study was the percentage of patients with HIV-1 RNA<200 copies/mL at week 12.

Results: 139 patients were randomized, 137 were included at D0 (G, n=69 pts/GP, n=68 pts) and 127 were followed up to week 12. At baseline median values were: HIV-1 RNA (log copies/mL: G=4.1; GP=4.0); CD4 cell count (/mm³; G=292; GP=294) and number of prior drugs (G=7; GP=8). Median number of resistance mutations was 8 in G group (NRTI=3; NNRTI=1; PI=4) and 10 in GP group (NRTI=4; NNRTI=2; PI=6). At week 8, ART was adjusted according to the PDM in 10/67 GP group patients (15%). By ITT missing equal failure analysis at week 12, an HIV-1 RNA<200 copies/mL was achieved in 30/69 patients (43%) in the G group vs 28/68 patients (41%) in the GP group (NS). At week 24, HIV-1 RNA<200 copies/mL was achieved in 34/59 patients (58%) in the G group vs 40/61 patients (66%) in the GP group; median drop in HIV-1 RNA level was -1.3 log copies/mL (-3.1 to 1.4) and -1.6 log copies/mL (-2.9 to 0.7) respectively (NS). At week 24, median increase of CD4 cell count was 59/mm³ (G) and 60/mm³ (GP)(NS). Correlation between PI/NNRTI PDM and virological responses are under analysis.

Conclusions: This study shows that combining genotypic resistance testing with the use of an expert committee to monitor individual subsequent therapy in patients with multiple resistance mutations was associated with a high antiviral efficacy with 62% of patients having < 200 copies/mL. The benefit of using PDM over 2 months was not evidenced in this study.