Clinical trial NCT00885482: Atazanavir and Lamivudine for Treatment Simplification
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV/AIDS
HAART
Simplification
Atazanavir
Lamivudine
treatment experienced
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
First posted: 2009-04-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 48 weeks
Secondary outcomes:
measure: Time to Virological Failure at Survival Analysis
timeFrame: 48 weeks
measure: Number of Patients With Viral Load Lower Than 50 Copies/mL at 48 Weeks at the Intention to Treat Analysis
timeFrame: 48 weeks
measure: Evolution of CD4 Cell Count During the 48 Weeks
timeFrame: 48 weeks
measure: Evolution of Adherence and Quality of Life During the 48 Weeks
timeFrame: 48 weeks
measure: Evolution of Atazanavir Plasma Concentrations During the 48 Weeks
timeFrame: 48 weeks
measure: Change of Metabolic Parameters at 48 Weeks
timeFrame: 48 weeks
measure: Change of the Results of Neurocognitive Tests at 48 Weeks
timeFrame: 48 weeks
measure: Change of Bone Density and of Subcutaneous Fat at 48 Weeks
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Catholic University of Sacred Heart
Study officials:
affiliation: Catholic University of Sacred Heart
name: Andrea De Luca, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.