Effect of Interleukin-2 on HIV Treatment Interruption
An Open-Label, Pilot Study Utilizing CD4 T-Cell Counts Lower Than 350 Cells/mm3 as the Threshold for Restarting Therapy With Potent Antiretroviral Therapy With or Without Interleukin-2 to Determine the Effect of Pulse Therapy on the Characteristics of Treatment Interruptions
調査の概要
詳細な説明
One approach in reconstituting an HIV-diminished immune system is the use of potent antiretroviral therapy (ART) in conjunction with IL-2. IL-2 is a cytokine secreted by activated T cells that regulates the proliferation and differentiation of CD4 and CD8 T cells. Although treatment with IL-2 can cause temporary increases in HIV viral load, clinical studies with IL-2 have revealed no long-term adverse effects on viral load. IL-2 therapy may also help purge the host's latent viral reservoir through activation of resting lymphocytes harboring provirus. Another approach to managing HIV infection is strategic treatment interruption. Results from small pilot trials suggest that HIV replication can be highly suppressed over consecutive courses of ART following short treatment interruptions, and CD4 T cell counts can be maintained on these interruptions with some positive effect on HIV-specific immunity. This study will evaluate potent ART, started and interrupted based on CD4 cell counts, with or without IL-2.
Patients will be stratified based on lifetime CD4 T-cell nadir (lowest measurement) into one of three groups. Group 1 will have a nadir of 200 CD4 cells/mm3; Group 2 will have a nadir greater than 200 CD4 cells/mm3; and patients with no documented nadir count available will join Group 3. Within each group, patients will be randomly assigned to one of two study arms. Arm A patients will receive pulses of potent ART with IL-2, while Arm B patients will receive pulses of potent ART alone. Patients in Arm A will receive potent ART with IL-2 given by subcutaneous injection twice daily for 5 days every 8 weeks for at least 17 weeks. Arm B patients will receive potent ART alone for at least 17 weeks. Both groups then go on treatment interruption for approximately 64 weeks, followed by potent ART alone for an additional 24 weeks. Patients will repeat this cycle of potent ART with or without IL-2, treatment interruption, and potent ART alone throughout the study. This study will last approximately 4 years.
Clinical and laboratory assessments will be performed periodically throughout the study. CD4 T cell counts and viral load will determine if a patient can enter the next treatment step. Potent ART is not provided by this study.
A5109s is a limited-center substudy designed to determine whether viral replication impairs lymphocyte proliferation in vivo. Patients at substudy-participating sites will register to the substudy immediately after beginning their first treatment interruption in the main study.
研究の種類
入学
段階
- 適用できない
連絡先と場所
研究場所
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California
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Los Angeles、California、アメリカ
- UCLA CARE Center CRS
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Palo Alto、California、アメリカ、943055107
- Stanford CRS
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San Jose、California、アメリカ
- Santa Clara Valley Med. Ctr.
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San Mateo、California、アメリカ、943055107
- San Mateo County AIDS Program
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Illinois
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Chicago、Illinois、アメリカ、60612
- Rush Univ. Med. Ctr. ACTG CRS
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Minnesota
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Minneapolis、Minnesota、アメリカ、55455
- University of Minnesota, ACTU
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Missouri
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Saint Louis、Missouri、アメリカ
- St. Louis ConnectCare, Infectious Diseases Clinic
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Saint Louis、Missouri、アメリカ、63108
- Washington U CRS
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Nebraska
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Omaha、Nebraska、アメリカ、681985130
- Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
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New York
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New York、New York、アメリカ、10003
- Beth Israel Med. Ctr., ACTU
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New York、New York、アメリカ
- Weill Med. College of Cornell Univ., The Cornell CTU
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New York、New York、アメリカ、10021
- Cornell CRS
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North Carolina
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Chapel Hill、North Carolina、アメリカ
- Unc Aids Crs
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Durham、North Carolina、アメリカ、27710
- Duke Univ. Med. Ctr. Adult CRS
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Ohio
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Cleveland、Ohio、アメリカ、44106
- Case CRS
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Cleveland、Ohio、アメリカ、441091998
- MetroHealth CRS
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15213
- Pitt CRS
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- HIV infected
- On stable, potent ART regimen for at least 3 months prior to study entry
- Viral load of less than 400 copies/ml for at least 6 months prior to study entry
- Viral load of less than 200 copies/ml at screening
- CD4 count of 500 cells/mm3 or greater at screening
- Agree to use acceptable methods of contraception
- Agree to be followed on this study for at least 4 years
- Primary care provider willing to have the patient in the study and to comply with study guidelines
Exclusion Criteria:
- Active or past significant AIDS-related illness. Patients with a history of minimal (less than 10 lesions) cutaneous Kaposi's sarcoma, pulmonary tuberculosis, or bacterial pneumonia are not excluded.
- Immunomodulators within 1 month of study entry
- Hydroxyurea within 3 months of study entry
- Prior IL-2 treatment
- Drugs to treat heart disease within 30 days of study entry
- Serious heart problems
- Cancer requiring anti-cancer drugs
- Thyroid problems. If the condition has been controlled by drugs for at least 3 months prior to study entry, the patient is not excluded.
- Uncontrolled diabetes
- Breathing or stomach problems that, in the opinion of the investigator, may affect the safety of the patient
- History of autoimmune disease, including inflammatory bowel disease, psoriasis, and optic neuritis
- Organ transplant
- History of neurological disorder or mental illness that, in the opinion of the investigator, may interfere with study requirements
- Alcohol or drug abuse that, in the opinion of the investigator, may interfere with study requirements
- Astemizole, midazolam, or triazolam within 2 weeks of study entry
- Systemic corticosteroids for 4 weeks or more within 3 months of study entry
- Pregnancy or breastfeeding
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
協力者と研究者
捜査官
- スタディチェア:W. Keith Henry, MD、HIV Program, Hennepin County Medical Center, University of Minnesota
出版物と役立つリンク
一般刊行物
- Conrad A. Interleukin-2--where are we going? J Assoc Nurses AIDS Care. 2003 Nov-Dec;14(6):83-8. doi: 10.1177/1055329003255620.
- Davey RT Jr, Murphy RL, Graziano FM, Boswell SL, Pavia AT, Cancio M, Nadler JP, Chaitt DG, Dewar RL, Sahner DK, Duliege AM, Capra WB, Leong WP, Giedlin MA, Lane HC, Kahn JO. Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: A randomized controlled trial. JAMA. 2000 Jul 12;284(2):183-9. doi: 10.1001/jama.284.2.183.
- Sullivan AK, Hardy GA, Nelson MR, Gotch F, Gazzard BG, Imami N. Interleukin-2-associated viral breakthroughs induce HIV-1-specific CD4 T cell responses in patients on fully suppressive highly active antiretroviral therapy. AIDS. 2003 Mar 7;17(4):628-9. doi: 10.1097/00002030-200303070-00020.
- Verheggen R. Immune restoration in patients with HIV infection: HAART and beyond. J Assoc Nurses AIDS Care. 2003 Nov-Dec;14(6):76-82. doi: 10.1177/1055329003259055.
- Xu J, Whitman L, Lori F, Lisziewicz J. Methods of using interleukin 2 to enhance HIV-specific immune responses. AIDS Res Hum Retroviruses. 2002 Mar 1;18(4):289-93. doi: 10.1089/088922202753472865.
- Henry K, Katzenstein D, Cherng DW, Valdez H, Powderly W, Vargas MB, Jahed NC, Jacobson JM, Myers LS, Schmitz JL, Winters M, Tebas P; A5102 Study Team of the AIDS Clinical Trials Group. A pilot study evaluating time to CD4 T-cell count <350 cells/mm(3) after treatment interruption following antiretroviral therapy +/- interleukin 2: results of ACTG A5102. J Acquir Immune Defic Syndr. 2006 Jun;42(2):140-8. doi: 10.1097/01.qai.0000225319.59652.1e.
- Tebas P, Henry WK, Matining R, Weng-Cherng D, Schmitz J, Valdez H, Jahed N, Myers L, Powderly WG, Katzenstein D. Metabolic and immune activation effects of treatment interruption in chronic HIV-1 infection: implications for cardiovascular risk. PLoS One. 2008 Apr 23;3(4):e2021. doi: 10.1371/journal.pone.0002021.
研究記録日
主要日程の研究
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
HIV感染症の臨床試験
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University of Alabama at BirminghamMobile County Health Deparment; Alabama Department of Public Health募集HIV | HIV検査 | HIV とケアの関係 | HIV治療アメリカ
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French National Agency for Research on AIDS and...Elizabeth Glaser Pediatric AIDS Foundation完了パートナーの HIV 検査 | カップルの HIV カウンセリング | カップルのコミュニケーション | HIV の発生率カメルーン, ドミニカ共和国, グルジア, インド
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University of Minnesota引きこもったHIV感染症 | HIV/エイズ | HIV | AIDS | エイズ・HIV問題 | エイズと感染症アメリカ
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Africa Health Research InstituteLondon School of Hygiene and Tropical Medicine; University College, London; University of Southampton と他の協力者募集
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ANRS, Emerging Infectious DiseasesHopital Universitaire Robert-Debre; Institut de Recherche pour le Developpement; Centre Pasteur... と他の協力者わからないHIV | HIVに感染していない子供たち | HIVにさらされた子供たちカメルーン
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Erasmus Medical Centerまだ募集していません
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University of Maryland, Baltimore引きこもった
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Hospital Clinic of Barcelona完了
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University of WashingtonNational Institute of Mental Health (NIMH)募集
アルデスロイキンの臨床試験
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Carman GiacomantonioNova Scotia Health Authority引きこもった
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Groupe Francophone des MyelodysplasiesEpiCept Corporation引きこもった