HIV/AIDSHIVNCT04088916
Proviral DNA as a Target for HIV-1 Resistance Analysis
An observational study of HIV/AIDS and HIV Infections, run by University of Chile at 2 sites in Chile.
Trial summary
In summary, in this project the investigators propose to study the proviral DNA genotyping to implement a lower cost and wider than the commercial systems currently in use, in order to analyze all HIV genes that are therapeutic targets of antiretroviral drugs. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV/AIDS, HIV Infections, HIV Seropositivity
- How many people
- 1,200 participants
- Where
- 2 sitesChile
- Study dates
- 15 Oct 2018to 31 Dec 2022
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Inclusion/Exclusion: Our Study will include only patients with HIV that had been confirmed by "Instituto de Salud Pública de Chile" (ISP-Chile). Children less than 18 years are excluded. Number of Patients: A total of 1,200 patients will be included in a period of three years (Including statistical justification, if appropriate)
Who may be able to join
- Clinical diagnosis of HIV
- viral load <1.000 copies/mL
- under antiretroviral tratment
Who cannot join
- HIV negative
- viral load >1.000 copies/mL
Trial locations and contacts
2 sites in 1 country.
Chile2 sites, 2 recruiting
- Recruiting
Immunology, HIV and Allergy Section
Santiago, Santiago Metropolitan
pablo ferrer, phd, +56950269199, pferrer@hcuch.cl
- Recruiting
Molecular Medicine Laboratory
Santiago, Santiago Metropolitan
pablo ferrer, phd, +56950269199, pferrer@hcuch.cl
About this study
In summary, in this project the investigators propose to study the proviral DNA genotyping to implement a lower cost and wider than the commercial systems currently in use, in order to analyze all HIV genes that are therapeutic targets of antiretroviral drugs. Using HIV proviral DNA we can obtain information for: HIV-1 Viral Tropism, Mutations associated to Integrase Inhibitors, Mutations associated to Transcriptase reverse Inhibitors, Mutations associated to Protease Inhibitors, and Mutations associated to GP41 Inhibitors.
Along with this the investigators propose to validate the proviral DNA as starting material for genotyping which is independent of the patient's viral load and achieve a greater number of patients living with HIV have access to this important test that is essential in monitoring the HIV infection.
Read more
3.2 RESEARCH QUESTIONs Is proviral DNA a genetic compartment suitable for carrying out a genotypic resistance test in patients with low or undetectable viral load? Does proviral DNA have the same clinical validity that RNA? 3.3.- HYPOTHESIS A resistance genotyping test carried out by Proviral DNA detects the same mutations associated to resistance that viral RNA.
3.4.- OBJECTIVES: General/Specific General objective Develop a methodology to assess the proviral HIV-1 DNA or RNA as the genetic material for genotyping assays in genes that are targets of pharmacological interest as TR reverse transcriptase and protease (PRO), Integrase or GP41 Inhibitors and HIV tropism. Specific Objectives
- Carry out genotyping by proviral DNA and compare it with the same genes genotyping performed with viral RNA. 2. Once the correlation between proviral DNA and RNA has shown, standardize a method to use the technique for clinical use in monitoring HIV patients according to each patient's needs. RNA for patients with viral load above 1,000 copies/mL. Proviral DNA for patients with low or undetectable viral load.
Read the detailed description
A prospective longitudinal observational study, the objective is to observe and describe the prevalence of INRT, INNRT, Protease and INIS mutations detected by proviral DNA in patients with virologic failure and low level viremia.
Inclusion/Exclusion: Our Study will include only patients with HIV that had been confirmed by "Instituto de Salud Pública de Chile" (ISP-Chile). Children less than 18 years are excluded.
Number of Patients: A total of 1,200 patients will be included in a period of three years (Including statistical justification, if appropriate).
- - Only patients who have signed informed consent will be admitted to our study.
- - The admitted patients will have a blood sample taken for an HIV genotypic resistance test.
- - from the clinical record of each patient admitted, some relevant clinical data will be taken to interpret the results such as CD4 T lymphocyte count, Viral Load, date of HIV diagnosis, date of initiation of therapy in addition to number and type of treatments antiretrovirals
- - By way of genotype control, a second blood sample will be taken every year.
Detailed Description
Detection of Resistance Mutations in Proviral DNA in HIV-1 Infection
Background The genetic test HIV proviral DNA (HPD) for resistance to antiretroviral drugs is very useful to detect mutations in patients under antiretroviral therapy who has failed to achieve undetectable viral loads levels or with low level viremia (LLV).
HPD allows the detection of circulating resistant variants and archived which could not be detected in the plasma.
HPD is independent of the viral load of patients. This makes it very useful for studies of primary resistance as it can detect resistance mutations in recently diagnosed patients with low baseline viral loads (<1,000 copies/mL).
HPD is recommended by the European AIDS Clinical Society EACS for cases where there is not HIV RNA for analysis (Barcelona, October 2015).
HPD is able to analyze resistance to all antiretroviral drugs currently available in the market. Therefore, with the HPD innovation we can carry out the following genetic resistance tests: HIV Tropism (Maraviroc), resistance to Integrase Inhibitors (Dolutegravir) and resistance to Transcriptase reversa/Proteasa (Abacavir).
Size Sample and Methodology
During a period of two years, we will study a population of 1,200 patients. These include all patients we have analyzed in our HIV center until December 2012. The methodology includes nucleic acid extraction, amplification of HIV-1 genes that are targets of therapeutic interest and sequencing by traditional and new generation sequencing methods.
Patient Recruitment: a Total of 1.200 (400 by year)
Obtaining blood samples: two samples: sample to the start and one sample to the end after one year
DNA and viral RNA extraction:
RT-PCR amplification:
Electrophoresis visualization in agarose gels
Sending samples to Macrogen for sequencing services
Automatic sequencing by Sanger method in Macrogen USA
Sequencing by deep sequencing (NGS) in Chile or Macrogen USA
Sequence Analysis
Quality Analysis and assemble of raw sequences in software ReCall
Registry of mutations of clinical interest
Report on resistance to antiretroviral drugs
Biostatistical analysis
Results Report and Publications
Preliminary results Preliminary analysis of 100 patients with viral load <1,000 copies/mL, detected 10% of patients with mutations of resistance to drugs that inhibit reverse transcriptase and viral protease. This valuable information enabled earlier therapeutic intervention by changing the drug scheme before they reach higher levels of viral load with consequent improvement in the clinical management.
Projections Project Due to the success and immediate application of this preliminary study, we believe it become very important to validate this technique as a daily routine genetic testing for HIV clinic patients in the public health system. Permanent financing for this genetic HIV test for HIV proviral DNA should be given by the Ministry of Health, Government of Chile.
In conclusion, at present HPD is very useful tool to study virologic failure and LLV in order to an early change of the antiretroviral therapy.
- Conditions
- HIV/AIDS, HIV Infections, HIV Seropositivity, Viral Infection
- Keywords
- ADNproviral, HIV, Resistance, genotyping
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections, HIV Seropositivity, Virus Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Proviral DNA as a Target for HIV-1 Resistance Analysis
Develop a methodology to assess the proviral HIV-1 DNA or RNA as the genetic material for genotyping assays in genes that are targets of pharmacological interest as TR reverse transcriptase and protease (PRO), Integrase or GP41 Inhibitors and HIV tropism
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2019
- Study start15 Oct 2018
- Primary completion8 Sep 2019
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 1,200 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- University of Chile
- Sponsor type
- University, hospital or other
- Collaborators
- ViiV Healthcare
- Responsible party
- Principal investigator, PABLO ANDRES FERRER CAMPOS, University of Chile
- Investigators
- Pablo Ferrer, Dr, Principal investigator, University of Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04088916
- Sponsor's protocol ID
- Nº OAIC 986/18
- Acronym
- HIV
- Status last verified
- Sep 2019
- First submitted
- 11 Sep 2019
- Last updated
- 17 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proviral DNA as a Target for HIV-1 Resistance Analysis
- ClinicalTrials.gov ID
- NCT04088916
- Acronym / sponsor ID
- HIV / Nº OAIC 986/18
- Conditions
- HIV/AIDS, HIV Infections, HIV Seropositivity, Viral Infection
- Keywords
- ADNproviral, HIV, Resistance, genotyping
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- University of ChileUniversity, hospital or other
- Collaborators
- ViiV Healthcare
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 8 Sep 2019 (actual)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 13 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In summary, in this project the investigators propose to study the proviral DNA genotyping to implement a lower cost and wider than the commercial systems currently in use, in order to analyze all HIV genes that are therapeutic targets of antiretroviral drugs. Using HIV proviral DNA we can obtain information for: HIV-1 Viral Tropism, Mutations associated to Integrase Inhibitors, Mutations associated to Transcriptase reverse Inhibitors, Mutations associated to Protease Inhibitors, and Mutations associated to GP41 Inhibitors.
Along with this the investigators propose to validate the proviral DNA as starting material for genotyping which is independent of the patient's viral load and achieve a greater number of patients living with HIV have access to this important test that is essential in monitoring the HIV infection.
3.2 RESEARCH QUESTIONs Is proviral DNA a genetic compartment suitable for carrying out a genotypic resistance test in patients with low or undetectable viral load? Does proviral DNA have the same clinical validity that RNA? 3.3.- HYPOTHESIS A resistance genotyping test carried out by Proviral DNA detects the same mutations associated to resistance that viral RNA.
3.4.- OBJECTIVES: General/Specific General objective Develop a methodology to assess the proviral HIV-1 DNA or RNA as the genetic material for genotyping assays in genes that are targets of pharmacological interest as TR reverse transcriptase and protease (PRO), Integrase or GP41 Inhibitors and HIV tropism. Specific Objectives
- Carry out genotyping by proviral DNA and compare it with the same genes genotyping performed with viral RNA. 2. Once the correlation between proviral DNA and RNA has shown, standardize a method to use the technique for clinical use in monitoring HIV patients according to each patient's needs. RNA for patients with viral load above 1,000 copies/mL. Proviral DNA for patients with low or undetectable viral load.
Detailed description
A prospective longitudinal observational study, the objective is to observe and describe the prevalence of INRT, INNRT, Protease and INIS mutations detected by proviral DNA in patients with virologic failure and low level viremia.
Inclusion/Exclusion: Our Study will include only patients with HIV that had been confirmed by "Instituto de Salud Pública de Chile" (ISP-Chile). Children less than 18 years are excluded.
Number of Patients: A total of 1,200 patients will be included in a period of three years (Including statistical justification, if appropriate).
- - Only patients who have signed informed consent will be admitted to our study.
- - The admitted patients will have a blood sample taken for an HIV genotypic resistance test.
- - from the clinical record of each patient admitted, some relevant clinical data will be taken to interpret the results such as CD4 T lymphocyte count, Viral Load, date of HIV diagnosis, date of initiation of therapy in addition to number and type of treatments antiretrovirals
- - By way of genotype control, a second blood sample will be taken every year.
Detailed Description
Detection of Resistance Mutations in Proviral DNA in HIV-1 Infection
Background The genetic test HIV proviral DNA (HPD) for resistance to antiretroviral drugs is very useful to detect mutations in patients under antiretroviral therapy who has failed to achieve undetectable viral loads levels or with low level viremia (LLV).
HPD allows the detection of circulating resistant variants and archived which could not be detected in the plasma.
HPD is independent of the viral load of patients. This makes it very useful for studies of primary resistance as it can detect resistance mutations in recently diagnosed patients with low baseline viral loads (<1,000 copies/mL).
HPD is recommended by the European AIDS Clinical Society EACS for cases where there is not HIV RNA for analysis (Barcelona, October 2015).
HPD is able to analyze resistance to all antiretroviral drugs currently available in the market. Therefore, with the HPD innovation we can carry out the following genetic resistance tests: HIV Tropism (Maraviroc), resistance to Integrase Inhibitors (Dolutegravir) and resistance to Transcriptase reversa/Proteasa (Abacavir).
Size Sample and Methodology
During a period of two years, we will study a population of 1,200 patients. These include all patients we have analyzed in our HIV center until December 2012. The methodology includes nucleic acid extraction, amplification of HIV-1 genes that are targets of therapeutic interest and sequencing by traditional and new generation sequencing methods.
Patient Recruitment: a Total of 1.200 (400 by year)
Obtaining blood samples: two samples: sample to the start and one sample to the end after one year
DNA and viral RNA extraction:
RT-PCR amplification:
Electrophoresis visualization in agarose gels
Sending samples to Macrogen for sequencing services
Automatic sequencing by Sanger method in Macrogen USA
Sequencing by deep sequencing (NGS) in Chile or Macrogen USA
Sequence Analysis
Quality Analysis and assemble of raw sequences in software ReCall
Registry of mutations of clinical interest
Report on resistance to antiretroviral drugs
Biostatistical analysis
Results Report and Publications
Preliminary results Preliminary analysis of 100 patients with viral load <1,000 copies/mL, detected 10% of patients with mutations of resistance to drugs that inhibit reverse transcriptase and viral protease. This valuable information enabled earlier therapeutic intervention by changing the drug scheme before they reach higher levels of viral load with consequent improvement in the clinical management.
Projections Project Due to the success and immediate application of this preliminary study, we believe it become very important to validate this technique as a daily routine genetic testing for HIV clinic patients in the public health system. Permanent financing for this genetic HIV test for HIV proviral DNA should be given by the Ministry of Health, Government of Chile.
In conclusion, at present HPD is very useful tool to study virologic failure and LLV in order to an early change of the antiretroviral therapy.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Target follow-up
- 1 Year
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Inclusion/Exclusion: Our Study will include only patients with HIV that had been confirmed by "Instituto de Salud Pública de Chile" (ISP-Chile). Children less than 18 years are excluded. Number of Patients: A total of 1,200 patients will be included in a period of three years (Including statistical justification, if appropriate)
Key inclusion criteria (3 listed)
- Clinical diagnosis of HIV
- viral load <1.000 copies/mL
- under antiretroviral tratment
Key exclusion criteria (2 listed)
- HIV negative
- viral load >1.000 copies/mL
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Proviral DNA as a Target for HIV-1 Resistance Analysis
Time frame: 3 years
Develop a methodology to assess the proviral HIV-1 DNA or RNA as the genetic material for genotyping assays in genes that are targets of pharmacological interest as TR reverse transcriptase and protease (PRO), Integrase or GP41 Inhibitors and HIV tropism
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pablo Ferrer, Dr principal investigator
University of Chile
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV/AIDS and HIV Infections, run by University of Chile at 2 sites in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proviral DNA as a Target for HIV-1 Resistance Analysis (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.