Francesca Lombardi1, Simone Belmonti1, Eugenia Quiros-Roldan2, Alessandra Latini3, Antonella Castagna4, Gabriella D'Ettorre5, Roberta Gagliardini1, Massimiliano Fabbiani6, Roberto Cauda1, Andrea De Luca7,8, Simona Di Giambenedetto1. 1. Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart of Rome, Rome, Italy. 2. University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. 3. Unit of Infectious Dermatology, San Gallicano Hospital, Rome, Italy. 4. Department of Infectious and Tropical Diseases, San Raffaele Scientific Institute, Milan, Italy. 5. Department of Infectious Diseases, 'La Sapienza' University, Rome, Italy. 6. Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. 7. Department of Medical Biotechnologies, University of Siena, Siena, Italy. 8. University Division of Infectious Diseases, Hospital Department of Specialized and Internal Medicine, Siena, Italy.
Abstract
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 reservoir 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 associated with the HIV-1 DNA levels were evaluated. Results: The mean baseline HIV-1 DNA levels (2.47 log 10 copies/10 6 leucocytes) were comparable between arms. A significant mean decrease between baseline and week 48 was observed: -0.069 log 10 copies/10 6 leucocytes 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 therapy 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 in terms of its effect on the cellular HIV-1 reservoir.
RCT Entities:
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 reservoir 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 associated with the HIV-1 DNA levels were evaluated. Results: The mean baseline HIV-1 DNA levels (2.47 log 10 copies/10 6 leucocytes) were comparable between arms. A significant mean decrease between baseline and week 48 was observed: -0.069 log 10 copies/10 6 leucocytes 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 therapy 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 in terms of its effect on the cellular HIV-1 reservoir.
Authors: Jonathan Z Li; Paul E Sax; Vincent C Marconi; Jesse Fajnzylber; Baiba Berzins; Amesika N Nyaku; Carl J Fichtenbaum; Timothy Wilkin; Constance A Benson; Susan L Koletar; Ramon Lorenzo-Redondo; Babafemi O Taiwo Journal: Open Forum Infect Dis Date: 2019-02-11 Impact factor: 3.835