Safety and feasibility of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients on stable treatment with two nucleos(t)ide reverse transcriptase inhibitors + atazanavir/ritonavir with virological suppression (Atazanavir and Lamivudine for treatment Simplification, AtLaS pilot study).
OBJECTIVE
To explore 48 week safety and efficacy of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression on a stable atazanavir/ritonavir-based standard triple regimen.


METHODS
This was a single-arm pilot study, enrolling 40 patients on atazanavir/ritonavir + two nucleos(t)ide reverse transcriptase inhibitors (NRTIs), without previous treatment failure, with HIV-RNA <50 copies/mL for >3 months and CD4 >200 cells/mm(3). At baseline, patients were switched to 300/100 mg of atazanavir/ritonavir + 300 mg of lamivudine once daily. Laboratory parameters, atazanavir plasma levels, self-reported adherence, quality of life, neurocognitive performance, bone composition and body fat distribution were monitored. Virological failure was defined as HIV-RNA >50 copies/mL on two consecutive determinations or a single level >1000 copies/mL.


RESULTS
After 48 weeks, 4/40 (10%) regimen discontinuations occurred: 1 death (brain haemorrhage), 1 study withdrawal (inadequate atazanavir plasma levels), 1 re-induction with two NRTIs due to pregnancy and 1 virological failure without development of resistance. Seven moderate to severe adverse events were recorded (including four renal colics, possibly treatment-related) in six patients. At week 48, increases in total (mean change +17 mg/dL, P = 0.001), high-density lipoprotein (+6 mg/dL, P < 0.001) and low-density lipoprotein (+8 mg/dL, P = 0.052) cholesterol were observed. The glomerular filtration rate improved (+7 mL/min/1.73 m(2), P < 0.001), as did scores exploring self-reported physical and mental health (+11, P = 0.009 and +13, P < 0.001 on a 0-100 scale), neuropsychological performance (-1 pathological task, P = 0.002) and total bone mineral density (+0.03 g/cm(2), P = 0.026). There were no significant changes in CD4 cell count, bilirubin, atazanavir plasma levels, adherence and body fat distribution over time.


CONCLUSIONS
Simplification to atazanavir/ritonavir + lamivudine was apparently safe and associated with rare virological failure, without resistance selection. This strategy deserves further investigation in a randomized trial.
Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
Simona
S
Di Giambenedetto
Massimiliano
M
Fabbiani
Manuela
M
Colafigli
Nicoletta
N
Ciccarelli
Salvatore
S
Farina
Letizia
L
Sidella
Alessandro
A
D'Avino
Annalisa
A
Mondi
Antonella
A
Cingolani
Enrica
E
Tamburrini
Rita
R
Murri
Pierluigi
P
Navarra
Roberto
R
Cauda
Andrea
A
De Luca
D050154:Adiposity / Q000187:drug effects; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D000069446:Atazanavir Sulfate; D001823:Body Composition / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D024882:Drug Resistance, Viral; D023381:Endpoint Determination; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000188:drug therapy* / Q000523:psychology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D010865:Pilot Projects; D011247:Pregnancy; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000069446:Atazanavir Sulfate; D019438:Ritonavir
combined antiretroviral therapy; dual therapy; long-term tolerability; switch