title: Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study.
abstract: OBJECTIVE
  AtLaS was a single-arm pilot study that demonstrated promising efficacy and safety of treatment simplification to a dual regimen with atazanavir/ritonavir + lamivudine in virologically suppressed HIV-positive patients. Here, we report data from the 144 week follow-up.
  
  
  METHODS
  At baseline, patients treated with a three-drug atazanavir/ritonavir-based regimen were switched to 300/100 mg of atazanavir/ritonavir plus 300 mg of lamivudine once daily. Major clinical events, laboratory parameters, neurocognitive performance, bone composition and body fat distribution were monitored. Treatment failure was defined as a discontinuation/switch of the regimen or virological failure (HIV-RNA >50 copies/mL in two consecutive determinations or a single level above 1000 copies/mL).
  
  
  RESULTS
  After 144 weeks, 9/40 (22.5%) treatment failures occurred, including two virological failures (Weeks 48 and 53, without resistance). A significant increase in the CD4 count was observed at Week 96 (+124 cells/mm(3); P = 0.002) and Week 144 (+94 cells/mm(3); P = 0.008). After 144 weeks, a significant increase in total cholesterol (+25 mg/dL; P = 0.001), HDL cholesterol (+6 mg/dL; P = 0.024) and LDL cholesterol (+12 mg/dL; P = 0.008) was observed, without any change in triglyceride levels, total cholesterol/HDL ratio or LDL/HDL ratio. A significant increase in the estimated glomerular filtration rate (+25 mL/min/1.73 m(2); P < 0.001) and lumbar spine T-score and Z-score (+0.2, P = 0.011; and +0.35, P = 0.001, respectively) and a decrease in trunk fat (-1.898 g; P = 0.005) were also observed. Neurocognitive function did not decline over time. Concerning safety, 10 moderate to severe adverse events were recorded in eight patients; overall seven cases of renal colic (possibly treatment related) were observed, leading to a discontinuation of treatment in two patients.
  
  
  CONCLUSIONS
  Data from the 144 week follow-up suggested good long-term efficacy of the simplification strategy that was investigated, with rare virological failure and a potential for improvement of the CD4 count, renal function and bone mineral density. This strategy warrants further investigation in a randomized trial.
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mondi
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy massifab@alice.it.
authors.forename: M
authors.initials: M
authors.lastname: Fabbiani
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Ciccarelli
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colafigli
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Avino
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Borghetti
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Gagliardini
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cauda
authors.affiliation: Infectious Diseases Unit, Siena University Hospital, Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Di Giambenedetto
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D000069446:Atazanavir Sulfate / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D000069446:Atazanavir Sulfate; D019438:Ritonavir
keywords: antiviral; combined antiretroviral therapy; dual therapy