Genotypic Resistant HIV Strains in Taiwan

NCT ID: NCT00954863

Last Updated: 2009-09-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-08-31

Study Completion Date

2010-07-31

Brief Summary

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Based on the investigators previous study, seventy-four of 786 HIV-1 isolates (9.4%), collected between 1999 to 2006, harbored one or more primary mutations associated with antiretroviral resistance to reverse-transcriptase inhibitors (RTIs) or protease inhibitors (PIs) in naïve patients. However, the drug resistance profiles for the HIV-1 integrase gene is unclear. Three objectives are proposed:

1. To investigate and compare the drug resistance profiles for the HIV-1 integrase gene between experienced and naive patients, who has not being exposed to Raltegravir.
2. To investigate and compare the drug resistance profiles for the HIV-1 integrase gene between different subtypes (subtype B, CRF01\_AE and CRF07\_BC).
3. To identify potential amino acid mutations in the integrase gene, which might affect the efficacy of Raltegravir.

Detailed Description

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From 2008 to 2009, blood samples will be collected from consecutive HIV-1-infected patients who received HIV care at the National Taiwan University Hospital. We expect to collect 100 cases who are antiretroviral naïve and 100 cases who are treatment-experienced patients. A standardized case collection form will be used to record data of demographics and clinical characteristics and laboratory results, such as plasma HIV RNA load (PVL) and CD4 cell counts. PVL will be quantified by the Cobas Amplicor HIV-1 MonitorTM Test, version 1.5, (Roche Diagnostics Corporation, Indianapolis, USA) according to manufacturer's protocol. The CD4 cell count will be determined using FACSFlow (Becton Dickinson). This study was approved by the Institutional Review Board of the hospital.

The in-house genotypic drug resistance test will be performed to determine the drug resistance profiles for the HIV-1 pol gene, focusing on protease, reverse transcriptase, and integrase. Drug resistance mutations will be identified with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database (http://hivdb.stanford.edu), in accordance with the drug-resistance mutation list of the International AIDS Society-USA Consensus Guidelines \[24\]. Strains with genetic mixtures of wild-type and mutant sequences at amino acid residues that code for major drug resistance will be considered to be drug resistant. Based on the interpretation given by the HIVdb program, sequences will be divided into the drug-resistant sequences, interpreted as having high, intermediate, and low levels of resistance, and the sensitive sequences, interpreted as the sensitive and potentially resistant. Multi-drug resistance (MDR) will be defined as having genotypic resistance to more than one class of antiretroviral drugs. Reference sequences of various subtypes and recombinants will be retrieved from the Los Alamos database (http://hiv-web.lanl.gov/seq-db.html). Sequences will be aligned with the Clustal W listed in the MEGA (molecular evolutionary genetics analysis) analytical package (version 3.0) \[25\] with minor manual adjustments. The phylogenetic trees will be constructed by the neighbor-joining method based on the Kimura 2-parameter distance matrix listed in the MEGA software. Bootstrap values greater than 750 of 1,000 replicates are considered significant.

The phenotype of those with specific or unique amino acid mutation at integrase gene will be determined using in-house phenotypic assay. Briefly, the p7 to vif fragment, about 3.6kb, will be amplified from patients' plasma viral RNA and cloned into our backbone viral clone (Figure 1). The resultant clones will be transfected into 293 cells to produce infectious viruses, whose titers will be determined by p24 assay and equal amounts of viruses will be subsequently used to infect PBMC from healthy donors. Virus titers in the supernatants from infected cells after 3, 5, and 7 days post infection in the presence or absence of tested compounds will be determined by real-time PCR or p24 assay. The minimal concentration of compounds required to reduce 50% of supernatant viral copies (EC50) will be calculated by regression analysis of the dose-response curves generated from real-time PCR or p24 assay.

Conditions

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HIV-1 HIV Infections

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* HIV-infected individuals

Exclusion Criteria

* No
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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National Taiwan University

Principal Investigators

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Sui-Yuan Chang, Sc. D.

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University

Locations

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R424, Examination Building, National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Sui-Yuan Chang, Sc. D.

Role: CONTACT

Phone: 886-2-23123456

Email: [email protected]

Facility Contacts

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Sui-Yuan Chang, Sc. D.

Role: primary

Other Identifiers

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200905045R

Identifier Type: -

Identifier Source: org_study_id