HIV Infections
Conditions
Keywords
HIV/AIDS, HAART, Simplification, Atazanavir, Lamivudine, treatment experienced
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.
Interventions
DRUGLamiduvine (Epivir)
Epivir 300 mg
Reyataz 300 mg
Norvir 100 mg
Sponsors
Catholic University of the Sacred Heart
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Time to Virological Failure at Survival Analysis | 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 |
| Evolution of Atazanavir Plasma Concentrations During the 48 Weeks | 48 weeks |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | low Therapeutic drug monitoring (TDM) | 1 |
| Overall Study | Pregnancy | 1 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants |
| Age, Continuous | 47 years STANDARD_DEVIATION 9 |
| Region of Enrollment Italy | 40 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 40 |
| serious Total, serious adverse events | 6 / 40 |
Outcome results
Primary
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
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm | 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 | 1 patients |
Secondary
Change of Bone Density and of Subcutaneous Fat at 48 Weeks
Time frame: 48 weeks
Secondary
Change of Metabolic Parameters at 48 Weeks
Time frame: 48 weeks
Secondary
Change of the Results of Neurocognitive Tests at 48 Weeks
Time frame: 48 weeks
Secondary
Evolution of Adherence and Quality of Life During the 48 Weeks
Time frame: 48 weeks
Secondary
Evolution of Atazanavir Plasma Concentrations During the 48 Weeks
Time frame: 48 weeks
Secondary
Evolution of CD4 Cell Count During the 48 Weeks
Time frame: 48 weeks
Secondary
Number of Patients With Viral Load Lower Than 50 Copies/mL at 48 Weeks at the Intention to Treat Analysis
Time frame: 48 weeks
Secondary
Time to Virological Failure at Survival Analysis
Time frame: 48 weeks