Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial

Background Growing evidence has linked HIV-1 resistance mutations and drug failure. The use of genotypic-resistance analysis to assist therapeutic dec ision-making in patients failing therapy has not been investigated. We asse ssed the virological and immunological impact of genotypic-resistance testi ng. Methods We did a prospective, open, randomised, controlled study of HIV-1-i nfected patients in whom combination therapy was not successful. We randoml y assigned patients standard care (control, n=43) or treatment according to the resistance mutations in protease and reverse-transcriptase genes (geno typic group, n=65), The major endpoint was the change in HIV-1 PNA viral lo ad. Analysis was by intention to treat. Findings 108 patients were enrolled, All patients were similar for risk fac tors, age, sex, previous treatment, CD4-cell count (214/mu L [SD14]) and lo g HIV-1 RNA Viral load at baseline (4.7 copies/mL [0.1]). At month 3, the m ean change in HIV-1 RNA was -1.04 log (0.14) in the study group compared wi th -0.46 log (0.17) in the control group (mean difference 0.58 log [95% CI 0.14-1.02], p=0.01). At month 6, changes were -1.15 (0.15) log copies/mL, a nd -0.67 (0.19) log copies/mL in the genotypic group and the control group, respectively (mean difference 0.48 log [0.01-0.97], p=0.05). Difference in the drop in viral load combined at 3 months and 6 months was significant ( p=0.015), At month 3, HIV-1 RNA was lower than detection level (200 copies/ mL) in 29% (19/65) of patients in the genotypic group versus 14% (6/43) in the control group (p=0.017). At month 6, the values were 32% (21/65) and 14 % (6/43) (p=0.067) for the genotypic group and the control group, respectiv ely. Therapy was generally well tolerated, with ten patients (six in the ge notypic group, four in the control group) requiring toxic-effect-related dr ug modification. Interpretation We found genotypic-resistance testing to have a significant benefit on the virological response when choosing a therapeutic alternative . Further study of the use of genotypic-resistance testing in assisting cli nical decisionmaking is warranted.