HIV-1NCT01168167
Impact of Raltegravir on HIV-1 cDNA Slope Following Antiretroviral Therapy (ART) Initiation
An observational study of HIV-1, run by Christoph Stephan at 1 site in Germany.
Trial summary
Recent clinical trials of combination antiretroviral therapy (cART) containing the first approved integrase inhibitor (i.e. raltegravir) have demonstrated a more rapid decay of HIV-1 RNA in plasma, compared to conventional potent antiretroviral combinations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2010to May 2012
- 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: Patients who begin cART in regular clinical routine with 2N(t)RTI plus either (n=10 patients) raltegravir or (n=10 patients) a boosted protease inhibitor/ alternatively an NNRTI as third substance will be offered to participate in this non-interventional study. Observation time is a period of 4 months after cART initiation.
Who may be able to join
- Initiation of antiretroviral therapy, consisting of 2 nucleoside/ nucleotide reverse transcriptase inhibitors at physician's disposition plus a third substance, i.e. either raltegravir (n=10 patients) or a standard third substance (efavirenz or boosted protease inhibitor)
- Men or women with a documented HIV-1 infection, treated at the study center
- age at least 18 years old
- physical examination and vital signs, according to the treating physician do not give any hint for a active AIDS-defining illness or other serious disease
- patients are naive to cART or in therapy interruption for at least 3 months
- last available HIV-1 RNA was >5,000 copies/mL within 3 months prior to cART initiation
- last available CD4-cell count showed at least 200 cells/µL within 3 months prior to cART initiation
- according to German-Austrian antiretroviral treatment recommendations, there is a given therapy indication
Who cannot join
- cART with other than the above mentioned drugs
- administration of concomitant drugs with relevant impact on antiretroviral's pharmacokinetics
- documented problems with patient visit- or medication-adherence
- any condition or disease requiring a medication that may interact relevantly with cART
Trial locations and contacts
1 site in 1 country.
Germany1 site
Johann Wolfgang Goethe-University Hospital
Frankfurt am Main, Hesse, 65520
About this study
Official title: Comparing the Dynamics of Different HIV-1 cDNA Species in CD4-positive T-cells and HIV-1 RNA in Plasma of Infected Individuals After Initiation of Antiretroviral Therapy With or Without Raltegravir
Recent clinical trials of combination antiretroviral therapy (cART) containing the first approved integrase inhibitor (i.e. raltegravir) have demonstrated a more rapid decay of HIV-1 RNA in plasma, compared to conventional potent antiretroviral combinations. This was observed especially during the early phase (up to week 12) following initiation of cART.
To explain this, two mechanistic hypotheses have been developed:
Read more
- - Macrophage reservoir death hypothesis. A major source of virus production during the second phase decay are believed to be long-lived infected cells with continuous virus production - e.g. macrophages. An accumulation of unintegrated, episomal HIV-1 cDNAs can promote apoptosis (Li et al. Embo J. 2001;20: 3272). In case of HIV superinfection of such a productively infected cell, an INI-based cART may induce apoptosis and thus contribute to a decrease in HIV RNA load during second phase decay. However, no study has thus far addressed the consequences of INI treatment on HIV-1 cDNA species on any cell population in vivo.
- - Resting CD4 T-cell reservoir integration block hypothesis. Resting CD4 T-cells may represent a substantial reservoir for HIV replication during the second phase decay as well. A special characteristic of these cells is that HIV-1 cDNA is typically localized to the nucleus in a not-integrated form (Chun et al., PNAS 1997;94:13193). These resting cells likely integrate HIV-DNA upon activation and then contribute to HIV viremia and viral spread. Conceptually, integration could be prevented by RGV, but not by RTI or PI. An accumulation of circular episomal HIV-1 cDNA species may also be a consequence of RGV treatment in this cell type.
Patient disposition:
To explore raltegravir-induced shifts in HIV-1 cDNA species in vivo, this non-interventional clinical observation investigates the dynamics of the three major HIV-1 cDNA species (total HIV-1 cDNA, HIV-1 integrants in the host cell genome, episomal HIV-1 2-LTR circles) over a period of 4 months in two groups of patients starting off cART from a single study center. Patients who begin cART in regular clinical routine with 2N(t)RTI plus either (n=10 patients) raltegravir or (n=10 patients) a boosted protease inhibitor/ alternatively an NNRTI will be offered to participate in this observation. Only patients are offered to participate in this trial if no other antiretroviral drugs than the above mentioned and no concomitant drugs with relevant impact on antiretroviral's pharmacokinetics are administered. At time of study inclusion, patients should be characterised by a HIV-1 RNA load of >5,000 copies/mL and CD4-cell count of >200/µL within 12 weeks before cART initiation.
Preliminary analyses of PBMCs from HIV-infected patients indicate that all three major HIV-1 cDNA species can be quantified by real-time PCR under these baseline conditions.
- Conditions
- HIV-1
- Keywords
- Antiretroviral Therapy, Highly Active, MK 0518, HIV-1 DNA species, viral slope, Ribonucleic Acid, DNA, Complementary
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 |
|---|---|---|
| raltegravir-based cART | Patients who begin cART in regular clinical routine with 2N(t)RTI plus raltegravir (n=10 patients) will be offered to participate in this observation arm, but only if no other antiretroviral drugs and no concomitant drugs with relevant impact on antiretroviral's pharmacokinetics are administered. At time of study inclusion, patients should be characterised by a HIV-1 RNA load of >5,000 copies/mL and CD4-cell count of >200/µL within 12 weeks before cART initiation. | |
| standard of care-cART | Patients who begin cART in regular clinical routine with 2N(t)RTI plus either a boosted protease inhibitor or efavirenz (n=10 patients) at standard doses will be offered to participate in this observation arm. They will be offered to participate in this trial only if no other antiretroviral drugs and no concomitant drugs with relevant impact on antiretroviral's pharmacokinetics are administered. At time of study inclusion, patients should be characterised by a HIV-1 RNA load of >5,000 copies/mL and CD4-cell count of >200/µL within 12 weeks before cART initiation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dynamical measurement of HIV-1 DNA-species extracted from whole blood-PBMCs
Measured: one year
Secondary outcomes (2)
CD4 cell counts
Measured: one year
plasma-HIV-1 RNA
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2010 (estimated)
- Study startJun 2010
- Primary completionMar 2011
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1Studies 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-control
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christoph Stephan
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Heidelberg
- Responsible party
- Sponsor-investigator, Christoph Stephan, Goethe University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01168167
- Sponsor's protocol ID
- JWG-HIVCENTER-Hopp1
- Status last verified
- Mar 2016
- First submitted
- 21 Jul 2010
- Last updated
- 23 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Stephan C, Baldauf HM, Barry J, Giordano FA, Bartholomae CC, Haberl A, Bickel M, Schmidt M, Laufs S, Kaderali L, Keppler OT. Impact of raltegravir on HIV-1 RNA and DNA forms following initiation of antiretroviral therapy in treatment-naive patients. J Antimicrob Chemother. 2014 Oct;69(10):2809-18. doi: 10.1093/jac/dku213. Epub 2014 Jun 23.
PubMed 24962031
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing the Dynamics of Different HIV-1 cDNA Species in CD4-positive T-cells and HIV-1 RNA in Plasma of Infected Individuals After Initiation of Antiretroviral Therapy With or Without Raltegravir
- ClinicalTrials.gov ID
- NCT01168167
- Acronym / sponsor ID
- JWG-HIVCENTER-Hopp1
- Conditions
- HIV-1
- Keywords
- Antiretroviral Therapy, Highly Active, MK 0518, HIV-1 DNA species, viral slope, Ribonucleic Acid, DNA, Complementary
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Christoph StephanUniversity, hospital or other
- Collaborators
- University Hospital Heidelberg
- Study start
- Jun 2010
- Primary completion
- Mar 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 23 Jul 2010 (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.
Recent clinical trials of combination antiretroviral therapy (cART) containing the first approved integrase inhibitor (i.e. raltegravir) have demonstrated a more rapid decay of HIV-1 RNA in plasma, compared to conventional potent antiretroviral combinations. This was observed especially during the early phase (up to week 12) following initiation of cART.
To explain this, two mechanistic hypotheses have been developed:
- - Macrophage reservoir death hypothesis. A major source of virus production during the second phase decay are believed to be long-lived infected cells with continuous virus production - e.g. macrophages. An accumulation of unintegrated, episomal HIV-1 cDNAs can promote apoptosis (Li et al. Embo J. 2001;20: 3272). In case of HIV superinfection of such a productively infected cell, an INI-based cART may induce apoptosis and thus contribute to a decrease in HIV RNA load during second phase decay. However, no study has thus far addressed the consequences of INI treatment on HIV-1 cDNA species on any cell population in vivo.
- - Resting CD4 T-cell reservoir integration block hypothesis. Resting CD4 T-cells may represent a substantial reservoir for HIV replication during the second phase decay as well. A special characteristic of these cells is that HIV-1 cDNA is typically localized to the nucleus in a not-integrated form (Chun et al., PNAS 1997;94:13193). These resting cells likely integrate HIV-DNA upon activation and then contribute to HIV viremia and viral spread. Conceptually, integration could be prevented by RGV, but not by RTI or PI. An accumulation of circular episomal HIV-1 cDNA species may also be a consequence of RGV treatment in this cell type.
Patient disposition:
To explore raltegravir-induced shifts in HIV-1 cDNA species in vivo, this non-interventional clinical observation investigates the dynamics of the three major HIV-1 cDNA species (total HIV-1 cDNA, HIV-1 integrants in the host cell genome, episomal HIV-1 2-LTR circles) over a period of 4 months in two groups of patients starting off cART from a single study center. Patients who begin cART in regular clinical routine with 2N(t)RTI plus either (n=10 patients) raltegravir or (n=10 patients) a boosted protease inhibitor/ alternatively an NNRTI will be offered to participate in this observation. Only patients are offered to participate in this trial if no other antiretroviral drugs than the above mentioned and no concomitant drugs with relevant impact on antiretroviral's pharmacokinetics are administered. At time of study inclusion, patients should be characterised by a HIV-1 RNA load of >5,000 copies/mL and CD4-cell count of >200/µL within 12 weeks before cART initiation.
Preliminary analyses of PBMCs from HIV-infected patients indicate that all three major HIV-1 cDNA species can be quantified by real-time PCR under these baseline conditions.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| raltegravir-based cART | – | –Patients who begin cART in regular clinical routine with 2N(t)RTI plus raltegravir (n=10 patients) will be offered to participate in this observation arm, but only if no other antiretroviral drugs and no concomitant drugs with relevant impact on antiretroviral's pharmacokinetics are administered. At time of study inclusion, patients should be characterised by a HIV-1 RNA load of >5,000 copies/mL and CD4-cell count of >200/µL within 12 weeks before cART initiation. |
| standard of care-cART | – | –Patients who begin cART in regular clinical routine with 2N(t)RTI plus either a boosted protease inhibitor or efavirenz (n=10 patients) at standard doses will be offered to participate in this observation arm. They will be offered to participate in this trial only if no other antiretroviral drugs and no concomitant drugs with relevant impact on antiretroviral's pharmacokinetics are administered. At time of study inclusion, patients should be characterised by a HIV-1 RNA load of >5,000 copies/mL and CD4-cell count of >200/µL within 12 weeks before cART initiation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who begin cART in regular clinical routine with 2N(t)RTI plus either (n=10 patients) raltegravir or (n=10 patients) a boosted protease inhibitor/ alternatively an NNRTI as third substance will be offered to participate in this non-interventional study. Observation time is a period of 4 months after cART initiation.
Key inclusion criteria (8 listed)
- Initiation of antiretroviral therapy, consisting of 2 nucleoside/ nucleotide reverse transcriptase inhibitors at physician's disposition plus a third substance, i.e. either raltegravir (n=10 patients) or a standard third substance (efavirenz or boosted protease inhibitor)
- Men or women with a documented HIV-1 infection, treated at the study center
- age at least 18 years old
- physical examination and vital signs, according to the treating physician do not give any hint for a active AIDS-defining illness or other serious disease
- patients are naive to cART or in therapy interruption for at least 3 months
Key exclusion criteria (4 listed)
- cART with other than the above mentioned drugs
- administration of concomitant drugs with relevant impact on antiretroviral's pharmacokinetics
- documented problems with patient visit- or medication-adherence
- any condition or disease requiring a medication that may interact relevantly with cART
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
Dynamical measurement of HIV-1 DNA-species extracted from whole blood-PBMCs
Time frame: one year
2 secondary outcomes
CD4 cell counts
Time frame: one year
plasma-HIV-1 RNA
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2016.
- Results publication: PubMed 24962031Stephan C, Baldauf HM, Barry J, Giordano FA, Bartholomae CC, Haberl A, Bickel M, Schmidt M, Laufs S, Kaderali L, Keppler OT. Impact of raltegravir on HIV-1 RNA and DNA forms following initiation of antiretroviral therapy in treatment-naive patients. J Antimicrob Chemother. 2014 Oct;69(10):2809-18. doi: 10.1093/jac/dku213. Epub 2014 Jun 23.
Related trials for HIV-1
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
RecruitingPhase 4
A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments
HIV-1-infection
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
Active, not recruitingPhase 3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy
HIV-1-infection
Active, not recruitingPhase 2/3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen (ARTISTRY-1)
HIV-1-infection
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.
The record lists no contact. Use the official record to reach the sponsor.
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, run by Christoph Stephan at 1 site in Germany.
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 8 inclusion and 4 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: finished, as of the sponsor's last update on 23 Mar 2016. 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 Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dynamical measurement of HIV-1 DNA-species extracted from whole blood-PBMCs (time frame: one year). 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 NCT01168167, which also lists 1 linked publication.
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 23 Mar 2016.