HIV-1 Infected PatientsNCT01381328
GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance
An observational study of HIV-1 Infected Patients and Fold-change Resistance, run by Università Vita-Salute San Raffaele at 1 site in Italy.
Trial summary
The purpose of this study is to correlate the different patterns of resistance mutations observed in vivo in patients failing RAL treatment with the fold-change resistance determined by the phenotypic assay. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1 Infected Patients, Fold-change Resistance, Resistance Mutations
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2011to Sep 2013
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: primary care clinic
Who may be able to join
- Adult (at least 18 years of age) treatment-experienced, HIV-infected subjects of either sex and of any race, failing to a RAL-containing regimen will be enrolled in the study
Who cannot join
- none
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Department of Infectious Diseases, IRCCS San Raffaele Hospital
Milan, 20127
Antonella Castagna, MD, 0039022643 ext. 7934, castagna.antonella@hsr.it
Elisabetta Carini, MSc, 0039022643 ext. 7934, carini.elisabetta@hsr.it
About this study
The purpose of this study is to correlate the different patterns of resistance mutations observed in vivo in patients failing RAL treatment with the fold-change resistance determined by the phenotypic assay.
Read the detailed description
The secondary objectives are, as follows:
- to establish standardised genotypic assay for the HIV-1 pol gene region (region of interest, sensitivity, mutations involved as primary or compensatory changes, role of polymorphism present at baseline).
- to reach consensus on the algorithm interpretation of in house ex-vivo genotypic evaluations.
- to assess the genetic changes in RAL-failing patients under continuous drug pressure or drug discontinuation (dynamics of the reversion of resistance mutations).
- to evaluate in RAL resistant HIV-1 variants the changes in replication capacity (RC) (baseline vs. following-timepoints).
- to evaluate the immunological and virological trend associated with a raltegravir-regimen failure.
- Keywords
- HIV-1 infected patients, RALTEGRAVIR regimen, genotypic evaluations, phenotypic evaluations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| RAL Group | HIV-1 infected patients failing to a RALTEGRAVIR-containing regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
- mean value of fold-change resistance determined by the phenotypic assay at baseline
Measured: baseline
Secondary outcomes (5)
changes of fold-change resistance determined by the phenotypic assay with respect to baseline.
Measured: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
genetic changes under continuous drug pressure or drug discontinuation with respect to baseline(dynamics of the reversion of resistance mutations)
Measured: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
changes of the replication capacity with respect to baseline
Measured: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
changes of HIV-RNA with respect to baseline
Measured: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
changes in CD4, CD4%, CD8, CD8% with respect to baseline
Measured: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startDec 2011
- Primary completionMar 2013 (estimated)
- Study completionSep 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for HIV-1 Infected PatientsStudies 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS San Raffaele, Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Elisabetta Carini, Università Vita-Salute San Raffaele
- Investigators
- Massimo Clementi, Prof., Principal investigator, University Vita-Salute San Raffaele Laboratory of Microbiology and VirologyAntonella Castagna, MD, Study director, Department of Infectious Diseases, IRCCS San Raffaele Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01381328
- Sponsor's protocol ID
- Gepheral
- Other IDs
- Merck Sharp & Dohme Corp.
- Status last verified
- Feb 2013
- First submitted
- 23 Jun 2011
- Last updated
- 11 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Engelman A, Mizuuchi K, Craigie R. HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell. 1991 Dec 20;67(6):1211-21. doi: 10.1016/0092-8674(91)90297-c.
PubMed 1760846Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov. 2005 Mar;4(3):236-48. doi: 10.1038/nrd1660.
PubMed 15729361Anker M, Corales RB. Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection. Expert Opin Investig Drugs. 2008 Jan;17(1):97-103. doi: 10.1517/13543784.17.1.97.
PubMed 18095922Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.
PubMed 17434401Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65. doi: 10.1056/NEJMoa0708978.
PubMed 18650513Canducci F, Sampaolo M, Marinozzi MC, Boeri E, Spagnuolo V, Galli A, Castagna A, Lazzarin A, Clementi M, Gianotti N. Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. AIDS. 2009 Feb 20;23(4):455-60. doi: 10.1097/QAD.0b013e328323da60.
PubMed 19165083Nakahara K, Wakasa-Morimoto C, Kobayashi M, Miki S, Noshi T, Seki T, Kanamori-Koyama M, Kawauchi S, Suyama A, Fujishita T, Yoshinaga T, Garvey EP, Johns BA, Foster SA, Underwood MR, Sato A, Fujiwara T. Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Antiviral Res. 2009 Feb;81(2):141-6. doi: 10.1016/j.antiviral.2008.10.007. Epub 2008 Nov 21.
PubMed 19027039Kobayashi M, Nakahara K, Seki T, Miki S, Kawauchi S, Suyama A, Wakasa-Morimoto C, Kodama M, Endoh T, Oosugi E, Matsushita Y, Murai H, Fujishita T, Yoshinaga T, Garvey E, Foster S, Underwood M, Johns B, Sato A, Fujiwara T. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res. 2008 Nov;80(2):213-22. doi: 10.1016/j.antiviral.2008.06.012. Epub 2008 Jul 14.
PubMed 18625269Ceccherini-Silberstein F, Malet I, D'Arrigo R, Antinori A, Marcelin AG, Perno CF. Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev. 2009 Jan-Mar;11(1):17-29.
PubMed 19290031Malet I, Delelis O, Valantin MA, Montes B, Soulie C, Wirden M, Tchertanov L, Peytavin G, Reynes J, Mouscadet JF, Katlama C, Calvez V, Marcelin AG. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother. 2008 Apr;52(4):1351-8. doi: 10.1128/AAC.01228-07. Epub 2008 Jan 28.
PubMed 18227187Menzo S, Monachetti A, Balotta C, Corvasce S, Rusconi S, Paolucci S, Baldanti F, Bagnarelli P, Clementi M. Processivity and drug-dependence of HIV-1 protease: determinants of viral fitness in variants resistant to protease inhibitors. AIDS. 2003 Mar 28;17(5):663-71. doi: 10.1097/01.aids.0000050852.71999.5f.
PubMed 12646788Sichtig N, Sierra S, Kaiser R, Daumer M, Reuter S, Schulter E, Altmann A, Fatkenheuer G, Dittmer U, Pfister H, Esser S. Evolution of raltegravir resistance during therapy. J Antimicrob Chemother. 2009 Jul;64(1):25-32. doi: 10.1093/jac/dkp153. Epub 2009 May 14.
PubMed 19447792Malet I, Delelis O, Soulie C, Wirden M, Tchertanov L, Mottaz P, Peytavin G, Katlama C, Mouscadet JF, Calvez V, Marcelin AG. Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. J Antimicrob Chemother. 2009 Apr;63(4):795-804. doi: 10.1093/jac/dkp014. Epub 2009 Feb 16.
PubMed 19221102
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GePheRal: Clinical Validation of the Genotypic Diagnosis of Hiv-1 Resistance to Raltegravir by Parallel Analysis of the Genotype and Phenotype Profiles of Resistance
- ClinicalTrials.gov ID
- NCT01381328
- Acronym / sponsor ID
- Gepheral
- Keywords
- HIV-1 infected patients, RALTEGRAVIR regimen, genotypic evaluations, phenotypic evaluations
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Collaborators
- IRCCS San Raffaele, Merck Sharp & Dohme LLC
- Study start
- Dec 2011
- Primary completion
- Mar 2013 (estimated)
- Study completion
- Sep 2013 (estimated)
- First posted
- 27 Jun 2011 (estimated)
- 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.
The purpose of this study is to correlate the different patterns of resistance mutations observed in vivo in patients failing RAL treatment with the fold-change resistance determined by the phenotypic assay.
Detailed description
The secondary objectives are, as follows:
- to establish standardised genotypic assay for the HIV-1 pol gene region (region of interest, sensitivity, mutations involved as primary or compensatory changes, role of polymorphism present at baseline).
- to reach consensus on the algorithm interpretation of in house ex-vivo genotypic evaluations.
- to assess the genetic changes in RAL-failing patients under continuous drug pressure or drug discontinuation (dynamics of the reversion of resistance mutations).
- to evaluate in RAL resistant HIV-1 variants the changes in replication capacity (RC) (baseline vs. following-timepoints).
- to evaluate the immunological and virological trend associated with a raltegravir-regimen failure.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAL Group | – | –HIV-1 infected patients failing to a RALTEGRAVIR-containing regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- primary care clinic
Key inclusion criteria (1 listed)
- Adult (at least 18 years of age) treatment-experienced, HIV-infected subjects of either sex and of any race, failing to a RAL-containing regimen will be enrolled in the study
Key exclusion criteria (1 listed)
- none
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
- mean value of fold-change resistance determined by the phenotypic assay at baseline
Time frame: baseline
5 secondary outcomes
changes of fold-change resistance determined by the phenotypic assay with respect to baseline.
Time frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
genetic changes under continuous drug pressure or drug discontinuation with respect to baseline(dynamics of the reversion of resistance mutations)
Time frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
changes of the replication capacity with respect to baseline
Time frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation.
changes of HIV-RNA with respect to baseline
Time frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
changes in CD4, CD4%, CD8, CD8% with respect to baseline
Time frame: 24 and 48 hours, W1, W2, W3 and W4 upon discontinuation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2013.
- Background: PubMed 1760846Engelman A, Mizuuchi K, Craigie R. HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell. 1991 Dec 20;67(6):1211-21. doi: 10.1016/0092-8674(91)90297-c.
- Background: PubMed 15729361Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov. 2005 Mar;4(3):236-48. doi: 10.1038/nrd1660.
- Background: PubMed 18095922Anker M, Corales RB. Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection. Expert Opin Investig Drugs. 2008 Jan;17(1):97-103. doi: 10.1517/13543784.17.1.97.
- Background: PubMed 17434401Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.
- Background: PubMed 18650513Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65. doi: 10.1056/NEJMoa0708978.
- Background: PubMed 19165083Canducci F, Sampaolo M, Marinozzi MC, Boeri E, Spagnuolo V, Galli A, Castagna A, Lazzarin A, Clementi M, Gianotti N. Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. AIDS. 2009 Feb 20;23(4):455-60. doi: 10.1097/QAD.0b013e328323da60.
- Background: PubMed 19027039Nakahara K, Wakasa-Morimoto C, Kobayashi M, Miki S, Noshi T, Seki T, Kanamori-Koyama M, Kawauchi S, Suyama A, Fujishita T, Yoshinaga T, Garvey EP, Johns BA, Foster SA, Underwood MR, Sato A, Fujiwara T. Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Antiviral Res. 2009 Feb;81(2):141-6. doi: 10.1016/j.antiviral.2008.10.007. Epub 2008 Nov 21.
- Background: PubMed 18625269Kobayashi M, Nakahara K, Seki T, Miki S, Kawauchi S, Suyama A, Wakasa-Morimoto C, Kodama M, Endoh T, Oosugi E, Matsushita Y, Murai H, Fujishita T, Yoshinaga T, Garvey E, Foster S, Underwood M, Johns B, Sato A, Fujiwara T. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res. 2008 Nov;80(2):213-22. doi: 10.1016/j.antiviral.2008.06.012. Epub 2008 Jul 14.
- Background: PubMed 19290031Ceccherini-Silberstein F, Malet I, D'Arrigo R, Antinori A, Marcelin AG, Perno CF. Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev. 2009 Jan-Mar;11(1):17-29.
- Background: PubMed 18227187Malet I, Delelis O, Valantin MA, Montes B, Soulie C, Wirden M, Tchertanov L, Peytavin G, Reynes J, Mouscadet JF, Katlama C, Calvez V, Marcelin AG. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother. 2008 Apr;52(4):1351-8. doi: 10.1128/AAC.01228-07. Epub 2008 Jan 28.
- Background: PubMed 12646788Menzo S, Monachetti A, Balotta C, Corvasce S, Rusconi S, Paolucci S, Baldanti F, Bagnarelli P, Clementi M. Processivity and drug-dependence of HIV-1 protease: determinants of viral fitness in variants resistant to protease inhibitors. AIDS. 2003 Mar 28;17(5):663-71. doi: 10.1097/01.aids.0000050852.71999.5f.
- Background: PubMed 19447792Sichtig N, Sierra S, Kaiser R, Daumer M, Reuter S, Schulter E, Altmann A, Fatkenheuer G, Dittmer U, Pfister H, Esser S. Evolution of raltegravir resistance during therapy. J Antimicrob Chemother. 2009 Jul;64(1):25-32. doi: 10.1093/jac/dkp153. Epub 2009 May 14.
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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.
Massimo Clementi, Prof. principal investigator
University Vita-Salute San Raffaele Laboratory of Microbiology and Virology
Antonella Castagna, MD study director
Department of Infectious Diseases, IRCCS San Raffaele Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1 Infected Patients and Fold-change Resistance, run by Università Vita-Salute San Raffaele at 1 site in Italy.
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 1 inclusion and 1 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 11 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
Contact Antonella Castagna, MD (0039022643 ext. 7934, castagna.antonella@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
- mean value of fold-change resistance determined by the phenotypic assay at baseline (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01381328, which also lists 13 linked publications.
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 11 Feb 2013.