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| ID | Type | Description | Link |
|---|---|---|---|
| 10023 | Registry Identifier | DAIDS ES |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Abacavir sulfate, Lamivudine, and Zidovudine | Drug | antiretroviral therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Levels of Proviral DNA in Peripheral Blood Mononuclear Cells (PBMC) (log10) | At 48 weeks after the start of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events Related to Study Medication | Grade 1-4 adverse events related to study medication | Up to 48 weeks |
| Proviral DNA Levels (log10) | At Week 24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Martin Markowitz, MD | Aaron Diamond AIDS Research Center | Study Chair |
| Susan Little, MD | Department of Medicine, University of California at San Diego | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota, ACTU | Minneapolis | Minnesota | 55455-0392 | United States | ||
| Beth Israel Med. Ctr., ACTU |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10651384 | Background | 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. | |
| 11877476 | Background | Rizzardi 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cyclosporine | The Cyclosporine arm (Arm A) will receive one tablet of abacavir sulfate (ABC), lamivudine (3TC), and zidovudine (AZT), (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. Abacavir sulfate, Lamivudine, and Zidovudine: antiretroviral therapy Lopinavir/Ritonavir: antiretroviral therapy |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Lopinavir/Ritonavir | Drug | antiretroviral therapy |
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| Proviral DNA (log10) | At Week 12 |
| HIV-1 Viral Load Levels | At Week 48 |
| Number of Patients With Viral Load Less Than 50 Copies/ml | Week 48 |
| CD4 T Cell Levels | At Week 48 |
| New York |
| New York |
| 10003 |
| United States |
| NY Univ. HIV/AIDS CRS | New York | New York | 10016-6481 | United States |
| MetroHealth CRS | Cleveland | Ohio | 44109-1998 | United States |
| 12003181 | Background | Rizzardi 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. |
| FG001 | No Cyclosporine | The No Cyclosporine arm (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 Abacavir sulfate, Lamivudine, and Zidovudine: antiretroviral therapy Lopinavir/Ritonavir: antiretroviral therapy |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | A: Cyclosporine | 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. Abacavir sulfate, Lamivudine, and Zidovudine: antiretroviral therapy Lopinavir/Ritonavir: antiretroviral therapy |
| BG001 | B: Placebo | 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 Abacavir sulfate, Lamivudine, and Zidovudine: antiretroviral therapy Lopinavir/Ritonavir: antiretroviral therapy |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Cluster of differentiation 4 (CD4+) T-cell count | Median | Inter-Quartile Range | cells/mm^3 |
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| Plasma log10 HIV viral load | Median | Inter-Quartile Range | log10(copies/mL) |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Levels of Proviral DNA in Peripheral Blood Mononuclear Cells (PBMC) (log10) | All participants completing week 48 visit. | Posted | Median | Inter-Quartile Range | log10(copies/mL) | At 48 weeks after the start of treatment |
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| Secondary | Adverse Events Related to Study Medication | Grade 1-4 adverse events related to study medication | Posted | Number | participants | Up to 48 weeks |
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| Secondary | Proviral DNA Levels (log10) | Posted | Median | Inter-Quartile Range | log10(copies/mL) | At Week 24 |
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| Secondary | Proviral DNA (log10) | Posted | Median | Inter-Quartile Range | log10(copies/mL) | At Week 12 |
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| Secondary | HIV-1 Viral Load Levels | Posted | Mean | 95% Confidence Interval | log10(copies/mL) | At Week 48 |
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| Secondary | Number of Patients With Viral Load Less Than 50 Copies/ml | Posted | Count of Participants | Participants | Week 48 |
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| Secondary | CD4 T Cell Levels | Posted | Median | Inter-Quartile Range | cells/mm^3 | At Week 48 |
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Up to 48 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cyclosporine | Cyclosporine 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. Abacavir sulfate, Lamivudine, and Zidovudine: antiretroviral therapy Lopinavir/Ritonavir: antiretroviral therapy | 0 | 36 | 1 | 36 | ||
| EG001 | No Cyclosporine | No Cyclosporine arm 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 Abacavir sulfate, Lamivudine, and Zidovudine: antiretroviral therapy Lopinavir/Ritonavir: antiretroviral therapy | 0 | 18 | 0 | 18 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Florin Vaida | University of California, San Diego | 619 543-8045 | fvaida@ucsd.edu |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C106538 | abacavir |
| D019259 | Lamivudine |
| D015215 | Zidovudine |
| C418262 | abacavir, lamivudine, and zidovudine drug combination |
| D061466 | Lopinavir |
| C558899 | lopinavir-ritonavir drug combination |
| ID | Term |
|---|---|
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015224 | Dideoxynucleosides |
| D013936 | Thymidine |
| D011744 | Pyrimidinones |
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| Male |
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| Hispanic |
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| African American |
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| Other |
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