Antiretroviral Resistance Detection by Ultrasensitive Pyrosequencing of the HIV-1 Genome and Virological Response to Antiretroviral Rescue Treatment

NCT01346878 | Completed

• 1 other identifier: PRIUS-2
• Study Type: observational
• Target: 143
• Locations: 1 country
• Sites: 4

Brief Summary

This study aims to analyze the association between the baseline detection of resistance mutations through Ultra deep Sequencing (UDS) and the virological outcome of salvage antiretroviral therapy, in comparison with conventional genotypic resistance tests. Based on the data generated in this study, new resistance interpretation tools and algorithms will be developed to improve the prediction of antiretroviral therapy outcomes. The final aim of the study is to improve the clinical care of HIV-1-infected patients through the incorporation of improved new antiretroviral resistances tests in the clinical practice.

Conditions

HIV

Keywords

Ultra deep sequencing; Virological failure; Salvage antiretroviral therapy

Outcome Measures

Primary Outcomes (1)

• Time to virological failure

  One year

Secondary Outcomes (6)

• Proportion of patients with VL <50 and <200 copies

  week 12 and 48

• Absolute decrease of viral load

  week 24 and 48

• Area under curve of viral load

  week 24 and 48

• CD4 increase

  week 24 and 48

• Comparison of virological failure rate associated with baseline genotypic resistance detection by conventional sequencing and ultrasensitive pyrosequencing of the HIV-1 genome.

  One year

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* PI GROUP: prior virologic failure of a Highly active antiretroviral therapy (HAART) regimen including a Protease inhibitor (PI) (ritonavir boosted or not), and a second consecutive start HAART regimen including a PI boosted with ritonavir + 2 Nucleoside Reverse Transcriptase Inhibitor (NRTI). The 6 months prior to the start of the second HAART regimen, are considered as a baseline. * NNRTI GROUP: Virologic failure after a HAART regimen that includes 1 Non Nucleoside Reverse Transcriptase Inhibitor (NNRTI) and 2 NRTIs, and beginning, consecutive or not, a rescue HAART regimen with etravirine, in combination with any other drug. The 6 months before starting rescue HAART regimen with etravirine, are considered as a baseline. * II GROUP: Virologic failure to any prior HAART and initiation of rescue HAART including raltegravir, in combination with any other drug. The 6 months before starting rescue HAART with raltegravir are considered as a baseline.

You may qualify if:

• Adults over 18 years old, HIV +, distributed in one of the following 3 treatment groups:
• PI GROUP: prior virologic failure of a HAART regimen including a PI (ritonavir boosted or not), and a second consecutive start HAART regimen including a PI boosted with ritonavir + 2 NRTIs. The 6 months prior to the start of the second HAART regimen, are considered as a baseline.
• NNRTI GROUP: Virologic failure after a HAART regimen that includes 1 NNRTI and 2 NRTIs, and beginning, consecutive or not, a rescue HAART regimen with etravirine, in combination with any other drug. The 6 months before starting rescue HAART regimen with etravirine, are considered as a baseline.
• II GROUP: Virologic failure to any prior HAART and initiation of rescue HAART including raltegravir, in combination with any other drug. The 6 months before starting rescue HAART with raltegravir are considered as a baseline.
• Sample of 1 mL of plasma available for pyrosequencing before starting rescue HAART.
• Viral load of HIV-1 \> 5,000 copies / mL at the time of obtaining the plasma sample.
• Any CD4 + count.
• Availability of clinical follow-up, viral load of HIV-1 and quarterly CD4 counts to at least 48 weeks after initiation of rescue HAART.
• Good adherence to therapy.
• The investigation period is in any event before the start of the study.

You may not qualify if:

• HIV-2 infection or HIV-1 subtype non-B.
• Poor adherence to therapy.
• Lack of adequate clinical and laboratory follow up.
• Non-compliance of the patient to participate in the study.

Sponsors & Collaborators

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

Study Sites (4)

Laboratorio de Retrovirología irsiCaixa

Badalona, Barcelona, 08916, Spain

Location

Mútua de Terrassa

Terrassa, Barcelona, 08227, Spain

Location

Hospital Universitario San Cecilio

Granada, Granada, 28012, Spain

Location

Hospital 12 de Octubre

Madrid, Madrid, 08041, Spain

Location

Related Publications (1)

• Pou C, Noguera-Julian M, Perez-Alvarez S, Garcia F, Delgado R, Dalmau D, Alvarez-Tejado M, Gonzalez D, Sayada C, Chueca N, Pulido F, Ibanez L, Rodriguez C, Casadella M, Santos JR, Ruiz L, Clotet B, Paredes R. Improved prediction of salvage antiretroviral therapy outcomes using ultrasensitive HIV-1 drug resistance testing. Clin Infect Dis. 2014 Aug 15;59(4):578-88. doi: 10.1093/cid/ciu287. Epub 2014 May 29.

  PMID: 24879788 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma samples

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: May 3, 2011
• Study Start: July 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: October 25, 2012

Record last verified: 2012-10

Locations

ES (4)