Genotypic Tropism Testing In Proviral Dna To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia

NCT ID: NCT01378910

Last Updated: 2019-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2014-05-31

Brief Summary

CCR5 antagonists might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity. The assessment of HIV-1 tropism in proviral DNA could be helpful to inform in which of these subjects CCR5 antagonists could be efficacious.

Detailed Description

The assessment of HIV-1 tropism is needed before starting treatment with a CCR5-antagonist. Several phenotypic and genotyping tropism tests have been developed in the recent years. Phenotypic assays (i.e. TrofileTM and ES-TrofileTM) have been used.in most clinical trials. Genotypic tropism testing, however, is easier, cheaper and faster than phenotypic methods, and can be performed in a local HIV laboratories.

Viral RNA amplification is difficult in subjects with HIV-1 RNA levels <500-1000 copies/mL. In these cases, the optimal source of genetic material is peripheral blood mononuclear cell (PBMC)-associated proviral DNA. Whereas genotypic tropism testing in proviral DNA is technically feasible, it has not been validated as a tool to predict sustained virological response to CCR5-antagonist therapy in subjects with undetectable viremia.

As of today, maraviroc is the only CCR5-antagonist approved for HIV treatment. It has few drug interactions and a good security profile, particularly in terms of lipid and glucose metabolism. Therefore, it might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity or metabolic problems.

This study will evaluate 48-week virological outcomes in aviremic subjects with an R5 virus by proviral genotypic tropism testing who switch the "third drug" of their regimen to maraviroc.

Conditions

HIV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Change of 3rd drug to maraviroc

Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

Group Type: EXPERIMENTAL

Unique

Intervention Type: DRUG

Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

Interventions

Unique

Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. HIV-1 infected patients.

2. Age 18 or more.

3. Antiretroviral treatment containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) plus 1 Non-nucleoside reverse-transcriptase inhibitor (NNRTI) or 1 protease inhibitor (PI) or 1 integrase inhibitor (ININ)

4. Patients receiving stable antiretroviral treatment for at least 6 months.

5. Viral load under 50 copies/mL in the last 6 months

6. Patients with CCR5 tropism based in V3 genotyping in proviral DNA using the G2P with a false positive rate of 10% interpretation method.

7. A change of treatment is needed due to toxicity / tolerability problems with the 3rd drug (PI, NNRTI or ININ), according to investigator criteria.

8. An antiretroviral regimen containing a CCR5-antagonist is suitable for the patient (physician criteria).

9. Voluntary written informed consent.

Exclusion Criteria

1. Pregnancy or breast-feeding.

2. Patient previously treated with maraviroc.

3. Patients with documented resistance to maraviroc or any other drug considered for the new ARV regimen.

4. Viral failure in the moment of inclusion.

5. Bad adherence history or anticipated (investigator criteria).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Xeral de Vigo

Santiago de Compostela, A Coruña, Spain

Hospital de Elche

Elche, Alicante, Spain

Hospital Son Espases

Palma de Mallorca, Balearic Islands, Spain

H. U. Germans Trias i Pujol

Badalona, Barcelona, Spain

H. de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital U. Marqués de Valdecilla

Santander, Cantabria, Spain

Hospital General de Castellón

Castellon, Castelló, Spain

Hospital Sta. Lucía/ H. Sta. Mª del Rosell

Cartagena, Murcia, Spain

Hospital de Cruces

Bilbao, Vizcaya, Spain

Hospital Gral. U. de Alicante

Alicante, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital de Mataró

Barcelona, , Spain

Hospital Virgen de las Nieves

Granada, , Spain

Hospital U. San Cecilio

Granada, , Spain

Hospital U. Gregorio Marañón

Madrid, , Spain

Hospital Carlos III

Madrid, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Reina Sofía de Murcia

Murcia, , Spain

Hospital Sant Pau i Santa Tecla

Tarragona, , Spain

Hospital La Fe

Valencia, , Spain

Hospital Gral. U. de Valencia

Valencia, , Spain

Hospital Arnau de Vilanova

Valencia, , Spain

Hospital U. Dr. Peset

Valencia, , Spain

Countries

Spain

Other Identifiers

PROTEST

Identifier Type: -

Identifier Source: org_study_id