Background. Although more economic and less time-consuming, VirtualPhenotype has not yet been compared with Real Phenotype. The objective was to compare viro-immunological response to salvage therapy selected after Real Phenotype vs VirtualPhenotype in patients failing HAART.

Methods. From 18 centres partecipating in the MaSTer project, 201 patients with >2-year-exposure to antiretrovirals and >6-drug-experience were enrolled. A 1:1 centralized randomization into Real Phenotype or VirtualPhenotype was performed. 87 patients in the Real Phenotype and 88 in the VirtualPhenotype arm have started therapy. Resistance-tests were performed at Virco NV, Mechelen, Belgium. Upon treatment history and resistance-results, an independent panel of experts advised on treatment choice for each patient. Resistance-results were interpreted by the old 4-10 laboratory cut-offs during the study, but the new Virco biological cut-offs were used for this analysis. Ahderence was measured by patient interviews and scored in 3 classes at 4, 8, and 12 months. We present interim analysis over a 12-month follow-up for 106 patients who reached the final time-point.

Results. The 2 arms were well matched at baseline by demographics, clinical stage, CD4+ count, and treatment history (class and length of exposure). Mean HIV-RNA was 4.8 Log₁₀ copies/mL in the Real Phenotype and 4.61 Log₁₀ copies/mL in the VirtualPhenotype arm (p=0.045). Overall, mean number of drugs experienced was 8.66, mean duration of previous treatment was 60 months. Patients were prescribed a mean of 3.04 drugs in the Real Phenotype and a mean of 2.84 drugs in the VirtualPhenotype arm (p=0.07). At least 3 sensitive-drugs were prescribed in the new regimens for 64.4% in Real Phenotype and for 61.4% in VirtualPhenotype arm. Proportions of HIV-RNA<400 copies/mL after 1, 4, 8, and 12 months were 17%, 19%, 31%, 26%, respectively, in the Real Phenotype and 16%, 21%, 29%, and 31% in the VirtualPhenotype arm on intent-to-treat analysis. The proportions of HIV-RNA reduction ≤ 0.5 Log₁₀ copies/mL were 32%, 50%, 39%, 42% in the Real Phenotype and 44%, 49%, 47%, 35% in the VirtualPhenotype arm. Mean CD4 increase was not different in the 2 groups. Adherence did not differ by arm, only <15% of patients having scarce compliance over the follow-up.

Conclusions. Both virological and immunological outcomes did not differ when real or virtual phenotype was used in this cohort of heavily pretreated patients. This result suggests equivalence between the 2 systems. Clinically meaningful reductions in the viral load were achieved even though undetectability was reached in a minority of patients.