Genotypic Resistant HIV Strains in Taiwan

September 28, 2009 updated by: National Taiwan University Hospital

Identification and Characterization of Genotypic Resistant HIV Strains in Taiwan

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.

Study Overview

Status

Unknown

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • Recruiting
        • R424, Examination Building, National Taiwan University Hospital
        • Contact:
        • Principal Investigator:
          • Sui-Yuan Chang, Sc. D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

HIV-infected individuals receiving clinical care at National Taiwan University Hospital

Description

Inclusion Criteria:

  • HIV-infected individuals

Exclusion Criteria:

  • No

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

  • Principal Investigator: Sui-Yuan Chang, Sc. D., National Taiwan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Anticipated)

July 1, 2010

Study Completion (Anticipated)

July 1, 2010

Study Registration Dates

First Submitted

August 5, 2009

First Submitted That Met QC Criteria

August 6, 2009

First Posted (Estimate)

August 7, 2009

Study Record Updates

Last Update Posted (Estimate)

September 29, 2009

Last Update Submitted That Met QC Criteria

September 28, 2009

Last Verified

August 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200905045R

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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