Simplification to Atazanavir/Ritonavir + Lamivudine as Maintenance Therapy

Phase 4

Completed

• Conditions: HIV Infection
• Interventions: Drug: Ritonavir boosted Atazanavir + Lamivudine; Drug: Ritonavir boosted Atazanavir + 2 NRTIs

• Registration Number: NCT01307488
• Lead Sponsor: Fundacion SEIMC-GESIDA

Brief Summary

A switch to a regimen consisting of ATV/RTV 300/100 mg QD + 3TC 300 mg QD in HIV-1 infected subjects in their first antiretroviral regimen and who are virologically suppressed on a regimen which consists of 2 NRTIs + any 3rd agent, is non-inferior to continue or switch to ATV/RTV 300/100 mg QD + 2 optimized NRTIs for maintenance of virological suppression.

Detailed Description

Clinical Trial, phase IV, randomized, open label, multicenter with approved drugs in their use conditions.

A switch to a regimen consisting of ATV/RTV 300/100 mg QD + 3TC 300 mg QD in HIV-1 infected subjects in their first antiretroviral regimen and who are virologically suppressed on a regimen which consists of 2 NRTIs + any 3rd agent, is non-inferior to continue or switch to ATV/RTV 300/100 mg QD + 2 optimized NRTIs for maintenance of virological suppression.

Study Timeline

• Study First Submitted: 2011-03-01
• Study First Submitted QC: 2011-03-02
• Study First Posted: 2011-03-03
• Study Start: 2011-09
• Primary Completion: 2014-04
• Study Completion: 2015-03
• Status Verified: 2015-05
• Last Update Submitted: 2015-05-08
• Last Update Posted: 2015-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 286

Inclusion Criteria

• Signature of informed consent
• At least 18 years old
• Patients on their 1st ARV treatment consisting on 2 NRTIs + 1 third agent for at least 1 year
• Undetectable viral load for at least 6 months prior to inclusion in the study (VL<50 c/mL in 2 determinations 6 months apart; blips are not allowed).
• Requirement of ARV treatment change due to toxicity, intolerance or simplification.
• Clinically stable.

Exclusion Criteria

• Pregnant women or women who plan to get pregnant during the study.
• Breast feeding
• History of change of any ARV treatment component for any reason 4 months prior to the inclusion in the trial
• History of ARV treatment change due to virological failure
• History of confirmed virological failure defined as one single VL >400 c/mL or at least 2 VL between 50 and 400 c/mL one year after an indetectable VL was achieved.
• Absence of HIV genotype prior to ARV treatment initiation.
• Resistance mutation to any of the study drugs (ATV, RTV, 3TC)
• HBV infection.
• History of toxicity or intolerance to ATV, RTV or 3TC.
• Gilbert's syndrome.
• Use of contraindicated drugs.
• Lab abnormalities grade 4.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ATV/r+3TC	Ritonavir boosted Atazanavir + Lamivudine	Subjects will receive ATV/RTV 300/100 mg QD + 2 optimized NRTIs for the first 4 weeks and then they will receive ATV/RTV 300/100 mg QD (once daily) and 3TC 300 mg QD for another 92 weeks. Treatment should be taken orally with a light meal at the same time each day.
ATV/r+2 NRTIs	Ritonavir boosted Atazanavir + 2 NRTIs	Subjects will receive ATV/RTV 300/100 mg QD + 2 optimized NRTIs for 96 weeks. Treatment should be taken orally with a light meal at the same time each day.

Primary Outcome Measures

Name	Time	Method
To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs	Week 48	Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 48 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs	week 96	Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 96 weeks of treatment
To assess safety after 24 weeks fo treatment	Week 24	Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities.; Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening.
To assess safety after 48 weeks fo treatment	Week 48	Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities.; Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening.
To assess safety after 96 weeks fo treatment	Week 96	Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities.; Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening.
To assess the incidence of resistance, and characterization of this resistance following a virological rebound	Week 96	Genotypic antiretroviral resistance profiles of subjects experiencing virologic failure (genotype) Plasma samples at Baseline and at each visit will be stored for additional resistance studies (i.e. cDNA)
To assess neurocognitive function evolution	Week 96	Nerocognitive function evolution measured through a battery of standardized tests from baseline to week 96

Trial Locations

Locations (36)

Hospital de Elche; 🇪🇸 Elche, Alicante, Spain

Hospital General de Granollers; 🇪🇸 Granollers, Barcelona, Spain

Hospital Marina Baixa; 🇪🇸 Villajoyosa, Alicante, Spain

H. Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

H. San Pedro; 🇪🇸 Logroño, La Rioja, Spain

Complexo Hospitalario Universitario de Santiago; 🇪🇸 Santiago de Compostela, La Coruña, Spain

Hospital de Jerez; 🇪🇸 Jerez de la Frontera, Cádiz, Spain

Hospital Clínico San Cecilio; 🇪🇸 Granada, Spain

Hospital de Santa Tecla; 🇪🇸 Tarragona, Spain

Hospital La Fe; 🇪🇸 Valencia, Spain

Hospital Juan Canalejo; 🇪🇸 La Coruña, Spain

Hospital Doce de Octubre; 🇪🇸 Madrid, Spain

Hospital Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital La Paz; 🇪🇸 Madrid, Spain

Hospital Virgen de la Victoria; 🇪🇸 Málaga, Spain

Hospital de Navarra; 🇪🇸 Pamplona, Spain

H. Universitario Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital Costa del Sol; 🇪🇸 Marbella, Málaga, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital de Mataró; 🇪🇸 Mataró, Spain

H. Universitario Son Espases; 🇪🇸 Mallorca, Spain

Hospital Donostia; 🇪🇸 San Sebastián, Spain

H. Juan Ramón Jiménez; 🇪🇸 Huelva, Spain

H. Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hospital de Basurto; 🇪🇸 Basurto, Vizcaya, Spain

Hospital Xeral Cíes; 🇪🇸 Vigo, Pontevedra, Spain

Hospital Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Arquitecto Marcide; 🇪🇸 El Ferrol, Pontevedra, Spain

H. Universitario Central de Asturias; 🇪🇸 Asturias, Spain

Hospital Príncipe de Asturias; 🇪🇸 Alcalá de Henares, Madrid, Spain

Hospital Severo Ochoa; 🇪🇸 Leganés, Madrid, Spain

Hospital General de Alicante; 🇪🇸 Alicante, Spain

Hospital Vall d'Hebrón; 🇪🇸 Barcelona, Spain