Evolution of blood-associated HIV-1 DNA levels after 48 weeks of switching to atazanavir/ritonavir+lamivudine dual therapy versus continuing triple therapy in the randomized AtLaS-M trial

Objectives: The AtLaS-M randomized trial showed that in patients with HIV-1 RNA ,50 copies/mL on atazanavir/ ritonavir ! two NRTIs, switching to a dual therapy with atazanavir/ritonavir!lamivudine had superior efficacy as compared with continuing the previous triple therapy. This substudy was designed to evaluate at 48 weeks the impact of the dual therapy versus the three-drug atazanavir/ritonavir-based therapy on the HIV-1 cellular reser- voir as reflected by the quantification of blood-associated HIV-1 DNA levels. Methods: In a representative subset of 201 of 266 randomized patients (104 in the dual-therapy arm and 97 in the triple-therapy arm) total HIV-1 DNA levels in whole blood at baseline and after 48 weeks and factors associ- ated with the HIV-1 DNA levels were evaluated. Results: The mean baseline HIV-1 DNA levels (2.47 log10 copies/106 leucocytes) were comparable between arms. A significant mean decrease between baseline and week 48 was observed: #0.069 log10 copies/106 leuco- cytes in the dual-therapy arm (P " 0.046) and #0.078 in the triple-therapy arm (P " 0.011); the mean difference between arms was #0.009 (P " 0.842). Nadir CD4 count was inversely correlated with baseline HIV-1 DNA (P " 0.009); longer duration of ART and lower nadir CD4 correlated with a less prominent HIV-1 DNA decrease (both P , 0.005). Higher baseline HIV-1 DNA was associated with residual viraemia at week 48 (P " 0.031). Conclusions: When compared with continuing three-drug therapy, atazanavir/ritonavir!lamivudine dual ther- apy resulted in a similar decline in HIV-1 DNA levels in patients with sustained virological suppression. These data support the safety of this simplified treatment strategy Introduction AtLaS-M was a randomized trial designed to evaluate the efficacy and safety of simplifying treatment to a dual regimen based on atazanavir/ritonavir!lamivudine as a single NRTI, as compared with continuing a triple atazanavir/ritonavir-based therapy in viro- logically controlled HIV-1-infected patients. At 48 weeks, the dual therapy was virologically superior and well tolerated.1 These find- ings confirmed the promising results of the previous single-arm AtLaS pilot study2,3 and were consistent with those of the SALT in terms of its effect on the cellular HIV-1 reservoir.