Atazanavir and Lamivudine for Treatment Simplification (AtLaS)

Pilot Study for the Evaluation of the Safety and the Feasibility of Treatment Simplification to Atazanavir/Ritonavir + Lamivudine in Patients Stably Treated With Two NRTIs + Atazanavir/Ritonavir With Optimal Virologic Response.

Objectives of the study:

1. To verify the safety of the study treatment, defined as the persistent control of the virus' replication at 48 weeks after the simplification to lamivudine + atazanavir with ritonavir.
2. To collect relevant information about the safety and the metabolic impact of this strategy in order to eventually design a non-inferiority randomized controlled trial for the evaluation of the safety and the efficacy of this strategy in the future.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lamiduvine (Epivir); Drug: Atazanavir (Reyataz); Drug: Ritonavir (Norvir)

Detailed Description

Combined antiretroviral therapy has greatly improved the natural history of HIV infection/AIDS. Yet, it is associated with important short- and long- term side effects. In particular, nucleoside and nucleotide analogs may cause anemia, pancreatitis, mitochondrial dysfunction, lactic acidosis, lipoatrophy and reduction of renal function or of bone density.

Our study aims to verify the safety and efficacy of a simplification of a dual therapy (Lamivudine plus Atazanavir with Ritonavir), confiding on the potency and high genetic barrier of ritonavir-boosted agents.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Catholic University Of Sacred Heart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients treated with the same regimen including 2NRTIs + ATV/r from at least 6 months
• Aged 18 years or older
• Who gave informed consent to the participation to the study
• With at least two viral load < 50 copies/mL in two consecutive determinations at least 3 months apart
• With CD4 cell count > 200 cells/μL and absence of any opportunistic infection or AIDS-related disease by one year at least

Exclusion Criteria:

• Pregnancy or breast feeding, desire of pregnancy in the short term
• Previous virological failure to antiretroviral therapy and/or previous exposure to mono- or dual therapies with reverse transcriptase nucleosidic analogues
• Patients with insufficient atazanavir plasma through concentration (lower than 0.23 μg/mL at 12th hour or 0.15 μg/mL at 24th hour) at screening and/or at baseline
• Patients with grade 3 or 4 laboratory abnormalities at screening (except for glucose or lipid serum levels and direct or indirect bilirubin)
• Concomitant treatment with antacids or proton-pump blockers or any other drug with known interactions or contraindications with the study medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; Treatment simplification from a "standard" combined antiretroviral therapy including 2 NRTIs and Atazanavir with Ritonavir to Lamivudine plus Atazanavir with Ritonavir. Treatment simplification from three-drugs- to two-drugs-based antiretroviral therapy.	Drug: Lamiduvine (Epivir); Epivir 300 mg; Drug: Atazanavir (Reyataz); Reyataz 300 mg; Drug: Ritonavir (Norvir); Norvir 100 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Virological Failure (Two Consecutive Measures of HIV-RNA Higher Than 50 Copies/mL or a Single Measure Higher Than 1000 Copies/mL) Within 48 Weeks at intention-to.Treat Analysis	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Virological Failure at Survival Analysis	48 weeks
Number of Patients With Viral Load Lower Than 50 Copies/mL at 48 Weeks at the Intention to Treat Analysis	48 weeks
Evolution of CD4 Cell Count During the 48 Weeks	48 weeks
Evolution of Adherence and Quality of Life During the 48 Weeks	48 weeks
Evolution of Atazanavir Plasma Concentrations During the 48 Weeks	48 weeks
Change of Metabolic Parameters at 48 Weeks	48 weeks
Change of the Results of Neurocognitive Tests at 48 Weeks	48 weeks
Change of Bone Density and of Subcutaneous Fat at 48 Weeks	48 weeks

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Andrea De Luca, MD, Catholic University Of Sacred Heart

Publications and helpful links

General Publications

• Fabbiani M, Bracciale L, Doino M, D'Avino A, Marzocchetti A, Navarra P, Cauda R, De Luca A, Di Giambenedetto S. Tenofovir discontinuation could predispose to urolithiasis in atazanavir-treated patients. J Infect. 2011 Apr;62(4):319-21. doi: 10.1016/j.jinf.2011.02.004. Epub 2011 Feb 15. No abstract available.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: April 20, 2009
• First Submitted That Met QC Criteria: April 20, 2009
• First Posted (Estimate): April 22, 2009

Study Record Updates

• Last Update Posted (Estimate): March 13, 2015
• Last Update Submitted That Met QC Criteria: February 23, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Lamivudine; Atazanavir; treatment experienced; HIV/AIDS; HAART; Simplification
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Atazanavir Sulfate
• Other Study ID Numbers: 2009-011273-32