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.
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.



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.



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).



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.
Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart of Rome, Rome, Italy.
Francesca
F
Lombardi
Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart of Rome, Rome, Italy.
Simone
S
Belmonti
University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
Eugenia
E
Quiros-Roldan
Unit of Infectious Dermatology, San Gallicano Hospital, Rome, Italy.
Alessandra
A
Latini
Department of Infectious and Tropical Diseases, San Raffaele Scientific Institute, Milan, Italy.
Antonella
A
Castagna
Department of Infectious Diseases, 'La Sapienza' University, Rome, Italy.
Gabriella
G
D'Ettorre
Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart of Rome, Rome, Italy.
Roberta
R
Gagliardini
Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
Massimiliano
M
Fabbiani
Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart of Rome, Rome, Italy.
Roberto
R
Cauda
Department of Medical Biotechnologies, University of Siena, Siena, Italy.|University Division of Infectious Diseases, Hospital Department of Specialized and Internal Medicine, Siena, Italy.
Andrea
A
De Luca
Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart of Rome, Rome, Italy.
Simona
S
Di Giambenedetto
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood* / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000069446:Atazanavir Sulfate; D019438:Ritonavir