HIV InfectionsPhase 2NCT00084149
Cyclosporine A in Combination With Abacavir Sulfate, Lamivudine, and Zidovudine and Lopinavir/Ritonavir in HIV
A Phase 2 study testing Abacavir sulfate, Lamivudine, and Zidovudine and Lopinavir/Ritonavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
Trial summary
Cyclosporine A (CsA) is a common long-term treatment used to inhibit the immune response in transplant patients who receive donor organs. CsA may also help people with HIV. The purpose of this study is to determine the safety of and immune response to CsA when given with abacavir sulfate (ABC), lamivudine (3TC), and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Abacavir sulfate, Lamivudine, and Zidovudine and Lopinavir/Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2004to Jan 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Acute HIV infection with HIV viral load of more than 50,000 copies/ml AND either negative ELISA OR Western blot with 5 bands or less within 4 weeks prior to study entry
- Hepatitis B surface antigen negative within 12 weeks prior to study entry
- Hepatitis C antibody negative within 12 weeks prior to study entry
- Willing to use acceptable methods of contraception
Who cannot join
- Prior antiretroviral therapy. A patient who has undergone Post Exposure Prophylaxis (PEP) taken at least 6 months prior to study entry is not excluded.
- Allergy or hypersensitivity to any study medications or their components
- Require certain medications, including those that may alter CsA levels or cause renal dysfunction. More information on this criterion can be found in the protocol.
- Any medical or psychiatric condition, including alcohol or drug abuse, that may interfere with adherence to study requirements
- Weight less than 88 lbs (40 kg)
- Uncontrolled hypertension
Show all 9Show fewer
- History of pancreatitis
- History of cancer. Participants with cancer in remission who have not had treatment for at least 3 years may be eligible for this study.
- Pregnancy or breastfeeding
Trial locations and contacts
4 sites in 1 country.
United States4 sites
MetroHealth CRS
Cleveland, Ohio, 44109-1998
University of Minnesota, ACTU
Minneapolis, Minnesota, 55455-0392
Beth Israel Med. Ctr., ACTU
New York, New York, 10003
NY Univ. HIV/AIDS CRS
New York, New York, 10016-6481
About this study
Official title: A Randomized Phase II Study of the Safety, Immunologic, and Virologic Effects of Cyclosporine A in Conjunction With Trizivir(R) and Kaletra(R) Versus Trizivir(R) and Kaletra(R) Alone During Primary HIV-1 Infection
Cyclosporine A (CsA) is a common long-term treatment used to inhibit the immune response in transplant patients who receive donor organs. CsA may also help people with HIV. The purpose of this study is to determine the safety of and immune response to CsA when given with abacavir sulfate (ABC), lamivudine (3TC), and zidovudine (AZT), (ABC/3TC/AZT) and lopinavir/ritonavir (LPV/r) to HIV infected adults in the early stages of infection.
Study hypothesis: The combination of CsA and LPV/r given to acutely infected individuals will result in lower levels of proviral DNA and latent infectious virus at 48 weeks compared to acute infected individuals treated with LPV/r alone.
Read the detailed description
During the early stages of HIV infection, HIV replicates unchecked, massive numbers of cluster of differentiation 4 (CD4) T cells are infected and destroyed, and other CD4 cells become infected but enter a latent phase. This latent pool of infected CD4 cells poses a difficult challenge in eliminating HIV infection during the early stages of infection because the cells persist for long periods, even with highly active effective antiretroviral therapy, and may later become active.
CsA is popularly used as a lifelong immunosuppressant for organ transplant patients. CsA inhibits cellular activation, including CD4 cell activation and proliferation. By reducing CD4 cell activation during acute HIV infection, fewer CD4 cells may be infected and die; more importantly, there may be fewer latent cells with the potential to become active later in the disease. However, CsA has many potential toxic effects, including renal damage, and may affect neurologic, endocrine, and hepatic organ systems.
In a previous small study of adults with acute HIV infection, a short 8-week course of CsA was well tolerated, and it is thought that a 4-week course of CsA may result in substantial reduction in both viral load and T cell activation, outweighing any potential toxic effects sustained during the one month treatment. This study will evaluate the safety of and immune response to a 4-week course of CsA with ABC/3TC/AZT and LPV/r compared to ABC/3TC/AZT and LPV/r alone in patients with acute HIV infection.
This 48-week study will randomly assign patients to one of two arms. During the first 4 weeks of the study, Arm A will receive one tablet of ABC/3TC/AZT twice daily, 3 capsules or 2 tablets of LPV/r twice daily, and liquid CsA (dose determined by weight) twice daily. At Week 5, Arm A patients will stop CsA but continue both ABC/3TC/AZT and LPV/r. Arm B will receive one tablet of ABC/3TC/AZT twice daily and 3 capsules or 2 tablets of LPV/r twice daily for all 48 weeks. On a case-by-case basis, an investigator may wish to prescribe ABC/3TC rather than ABC/3TC/AZT at initial therapy. Participants with ABC hypersensitivity will be given 3TC/AZT instead of ABC/3TC/AZT.
A complete physical exam and medical history assessment will occur at study entry and at Week 48. Study visits will occur every week until Week 4, then every 4 weeks until the end of the study. Blood and urine collection and clinical assessments will occur at each study visit. Additionally, patients in Arm A only will undergo CsA level monitoring at Day 3 and Weeks 1, 2, and 3; CsA dosage may be adjusted as necessary.
- Conditions
- HIV Infections
- Being tested
- Abacavir sulfate, Lamivudine, and Zidovudine, Lopinavir/Ritonavir
- Keywords
- Acute Infection, Treatment Naive
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abacavir sulfate, Lamivudine, and ZidovudineDrug
Also called Trizivir
antiretroviral therapy
Lopinavir/RitonavirDrug
Also called Kaletra
antiretroviral therapy
| Study group | Role | What they receive |
|---|---|---|
| Cyclosporin | Experimental | Cyclosporin arm (Arm A) will receive one tablet of Abacavir sulfate, Lamivudine, and Zidovudine (ABC/3TC/AZT) twice daily, 3 capsules or 2 tablets of lopinavir/ritonavir (LPV/r) twice daily, and liquid cyclosporin A (CsA) (dose determined by weight) twice daily. At Week 5, Arm A patients will stop CsA but continue both ABC/3TC/AZT and LPV/r. Receives: Drug: Abacavir sulfate, Lamivudine, and Zidovudine; Drug: Lopinavir/Ritonavir |
| No Cyclosporin | Experimental | The No Cyclosporin arm (Arm B) will receive one tablet of Abacavir sulfate, Lamivudine, and Zidovudine (ABC/3TC/AZT) twice daily and 3 capsules or 2 tablets of lopinavir/ritonavir (LPV/r) twice daily for all 48 weeks Receives: Drug: Abacavir sulfate, Lamivudine, and Zidovudine; Drug: Lopinavir/Ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of Proviral DNA in Peripheral Blood Mononuclear Cells (PBMC) (log10)
Measured: At 48 weeks after the start of treatment
Secondary outcomes (6)
Adverse Events Related to Study Medication
Grade 1-4 adverse events related to study medication
Measured: Up to 48 weeks
Proviral DNA Levels (log10)
Measured: At Week 24
Proviral DNA (log10)
Measured: At Week 12
HIV-1 Viral Load Levels
Measured: At Week 48
Number of Patients With Viral Load Less Than 50 Copies/ml
Measured: Week 48
CD4 T Cell Levels
Measured: At Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2004 (estimated)
- Study startFeb 2004
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Martin Markowitz, MD, Study chair, Aaron Diamond AIDS Research CenterSusan Little, MD, Study chair, Department of Medicine, University of California at San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00084149
- Sponsor's protocol ID
- AIN501/A5216
- Other IDs
- 10023
- Status last verified
- Aug 2018
- First submitted
- 7 Jun 2004
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ravot E, Lisziewicz J, Lori F. New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide. Drugs. 1999 Dec;58(6):953-63. doi: 10.2165/00003495-199958060-00001.
PubMed 10651384Rizzardi GP, Harari A, Capiluppi B, Tambussi G, Ellefsen K, Ciuffreda D, Champagne P, Bart PA, Chave JP, Lazzarin A, Pantaleo G. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy. J Clin Invest. 2002 Mar;109(5):681-8. doi: 10.1172/JCI14522.
PubMed 11877476Rizzardi GP, Lazzarin A, Pantaleo G. Potential role of immune modulation in the effective long-term control of HIV-1 infection. J Biol Regul Homeost Agents. 2002 Jan-Mar;16(1):83-90.
PubMed 12003181
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of the Safety, Immunologic, and Virologic Effects of Cyclosporine A in Conjunction With Trizivir(R) and Kaletra(R) Versus Trizivir(R) and Kaletra(R) Alone During Primary HIV-1 Infection
- ClinicalTrials.gov ID
- NCT00084149
- Acronym / sponsor ID
- AIN501/A5216
- Conditions
- HIV Infections
- Keywords
- Acute Infection, Treatment Naive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Feb 2004
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 8 Jun 2004 (estimated)
- Results
- Posted 13 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cyclosporine A (CsA) is a common long-term treatment used to inhibit the immune response in transplant patients who receive donor organs. CsA may also help people with HIV. The purpose of this study is to determine the safety of and immune response to CsA when given with abacavir sulfate (ABC), lamivudine (3TC), and zidovudine (AZT), (ABC/3TC/AZT) and lopinavir/ritonavir (LPV/r) to HIV infected adults in the early stages of infection.
Study hypothesis: The combination of CsA and LPV/r given to acutely infected individuals will result in lower levels of proviral DNA and latent infectious virus at 48 weeks compared to acute infected individuals treated with LPV/r alone.
Detailed description
During the early stages of HIV infection, HIV replicates unchecked, massive numbers of cluster of differentiation 4 (CD4) T cells are infected and destroyed, and other CD4 cells become infected but enter a latent phase. This latent pool of infected CD4 cells poses a difficult challenge in eliminating HIV infection during the early stages of infection because the cells persist for long periods, even with highly active effective antiretroviral therapy, and may later become active.
CsA is popularly used as a lifelong immunosuppressant for organ transplant patients. CsA inhibits cellular activation, including CD4 cell activation and proliferation. By reducing CD4 cell activation during acute HIV infection, fewer CD4 cells may be infected and die; more importantly, there may be fewer latent cells with the potential to become active later in the disease. However, CsA has many potential toxic effects, including renal damage, and may affect neurologic, endocrine, and hepatic organ systems.
In a previous small study of adults with acute HIV infection, a short 8-week course of CsA was well tolerated, and it is thought that a 4-week course of CsA may result in substantial reduction in both viral load and T cell activation, outweighing any potential toxic effects sustained during the one month treatment. This study will evaluate the safety of and immune response to a 4-week course of CsA with ABC/3TC/AZT and LPV/r compared to ABC/3TC/AZT and LPV/r alone in patients with acute HIV infection.
This 48-week study will randomly assign patients to one of two arms. During the first 4 weeks of the study, Arm A will receive one tablet of ABC/3TC/AZT twice daily, 3 capsules or 2 tablets of LPV/r twice daily, and liquid CsA (dose determined by weight) twice daily. At Week 5, Arm A patients will stop CsA but continue both ABC/3TC/AZT and LPV/r. Arm B will receive one tablet of ABC/3TC/AZT twice daily and 3 capsules or 2 tablets of LPV/r twice daily for all 48 weeks. On a case-by-case basis, an investigator may wish to prescribe ABC/3TC rather than ABC/3TC/AZT at initial therapy. Participants with ABC hypersensitivity will be given 3TC/AZT instead of ABC/3TC/AZT.
A complete physical exam and medical history assessment will occur at study entry and at Week 48. Study visits will occur every week until Week 4, then every 4 weeks until the end of the study. Blood and urine collection and clinical assessments will occur at each study visit. Additionally, patients in Arm A only will undergo CsA level monitoring at Day 3 and Weeks 1, 2, and 3; CsA dosage may be adjusted as necessary.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclosporin | Experimental | Drug: Abacavir sulfate, Lamivudine, and Zidovudine, Drug: Lopinavir/RitonavirCyclosporin arm (Arm A) will receive one tablet of Abacavir sulfate, Lamivudine, and Zidovudine (ABC/3TC/AZT) twice daily, 3 capsules or 2 tablets of lopinavir/ritonavir (LPV/r) twice daily, and liquid cyclosporin A (CsA) (dose determined by weight) twice daily. At Week 5, Arm A patients will stop CsA but continue both ABC/3TC/AZT and LPV/r. |
| No Cyclosporin | Experimental | Drug: Abacavir sulfate, Lamivudine, and Zidovudine, Drug: Lopinavir/RitonavirThe No Cyclosporin arm (Arm B) will receive one tablet of Abacavir sulfate, Lamivudine, and Zidovudine (ABC/3TC/AZT) twice daily and 3 capsules or 2 tablets of lopinavir/ritonavir (LPV/r) twice daily for all 48 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Acute HIV infection with HIV viral load of more than 50,000 copies/ml AND either negative ELISA OR Western blot with 5 bands or less within 4 weeks prior to study entry
- Hepatitis B surface antigen negative within 12 weeks prior to study entry
- Hepatitis C antibody negative within 12 weeks prior to study entry
- Willing to use acceptable methods of contraception
Key exclusion criteria (9 listed)
- Prior antiretroviral therapy. A patient who has undergone Post Exposure Prophylaxis (PEP) taken at least 6 months prior to study entry is not excluded.
- Allergy or hypersensitivity to any study medications or their components
- Require certain medications, including those that may alter CsA levels or cause renal dysfunction. More information on this criterion can be found in the protocol.
- Any medical or psychiatric condition, including alcohol or drug abuse, that may interfere with adherence to study requirements
- Weight less than 88 lbs (40 kg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abacavir sulfate, Lamivudine, and ZidovudineAlso: Trizivirantiretroviral therapy | Drug | Cyclosporin, No Cyclosporin |
| Lopinavir/RitonavirAlso: Kaletraantiretroviral therapy | Drug | Cyclosporin, No Cyclosporin |
Primary outcome
Levels of Proviral DNA in Peripheral Blood Mononuclear Cells (PBMC) (log10)
Time frame: At 48 weeks after the start of treatment
6 secondary outcomes
Adverse Events Related to Study Medication
Time frame: Up to 48 weeks
Proviral DNA Levels (log10)
Time frame: At Week 24
Proviral DNA (log10)
Time frame: At Week 12
HIV-1 Viral Load Levels
Time frame: At Week 48
Number of Patients With Viral Load Less Than 50 Copies/ml
Time frame: Week 48
CD4 T Cell Levels
Time frame: At Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10651384Ravot E, Lisziewicz J, Lori F. New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide. Drugs. 1999 Dec;58(6):953-63. doi: 10.2165/00003495-199958060-00001.
- Background: PubMed 11877476Rizzardi GP, Harari A, Capiluppi B, Tambussi G, Ellefsen K, Ciuffreda D, Champagne P, Bart PA, Chave JP, Lazzarin A, Pantaleo G. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy. J Clin Invest. 2002 Mar;109(5):681-8. doi: 10.1172/JCI14522.
- Background: PubMed 12003181Rizzardi GP, Lazzarin A, Pantaleo G. Potential role of immune modulation in the effective long-term control of HIV-1 infection. J Biol Regul Homeost Agents. 2002 Jan-Mar;16(1):83-90.
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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.
Martin Markowitz, MD study chair
Aaron Diamond AIDS Research Center
Susan Little, MD study chair
Department of Medicine, University of California at San Diego
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abacavir sulfate, Lamivudine, and Zidovudine and Lopinavir/Ritonavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
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 4 inclusion and 9 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 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Levels of Proviral DNA in Peripheral Blood Mononuclear Cells (PBMC) (log10) (time frame: At 48 weeks after the start of treatment). 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 NCT00084149, which also lists 3 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 4 Nov 2021.