Augmenting the Magnitude of HAART-Induced Immune Restoration With the Use of Cyclosporine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 15
研究概览
简要总结
The purpose of this study is to see if cyclosporine, taken when a patient begins highly active antiretroviral therapy (HAART), increases the number of CD4 T-cells (blood cells that fight infection) in a patient's blood. This study also will explore the safety of briefly giving cyclosporine to patients starting HAART.
详细描述
The availability of HAART has substantially decreased the morbidity and mortality caused by HIV-1 infection. There is clinical and laboratory evidence suggesting that treatment of HIV-1 infection not only arrests the progressive immune deterioration caused by HIV-1, but also is associated with at least partial immune reconstitution. After starting HAART, most patients with chronic HIV-1 infection experience an increase in CD4 T-cells, but the magnitude of CD4 lymphocyte rise is highly variable. Patients who do not experience a substantial rise in circulating CD4 lymphocytes remain at risk for opportunistic infections. Strategies to enhance immune restoration in HIV-1 disease are needed. Studies have shown that immune restoration after HAART in patients with chronic HIV-1 infection is incomplete. There are, however, several potential methods that can be used that possibly may enhance the magnitude of CD4 lymphocyte rise induced by HAART. It is proposed that the lymphoid tissues, in which lymphocytes are trapped and activated to die, are a major site of immunopathology and cellular losses in HIV-infection. Interference with lymphocyte trapping and death in lymphoid tissues when cyclosporine, an immunosuppressant, is administered at the time of initiation of HAART may result in an enhancement of the magnitude of cellular restoration in patients who initiate HAART.
Patients are randomized to 1 of 2 treatment arms:
Arm A: Weeks 1 to 2: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV). Weeks 3 to 48: ABC/3TC/ZDV and efavirenz (EFV).
Arm B: Weeks 1 to 2: ABC/3TC/ZDV and cyclosporine. Weeks 3 to 48: ABC/3TC/ZDV and EFV.
Patients in both arms receive the following immunizations: Weeks 8 and 12: Hepatitis A vaccine inactivated and rabies vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients may be eligible for this study if they:
- •Are HIV infected.
- •Have received no more than 7 days of any anti-HIV treatment prior to study entry and not within 3 weeks of study entry.
- •Have a CD4 cell count greater than 100 cells/mm3 within 30 days prior to study entry.
- •Have a viral load greater than 5000 copies/ml within 30 days prior to study entry.
- •Agree not to become pregnant or to impregnate during the study. The female/male partners must use 2 acceptable methods of contraception while receiving drugs and for 6 weeks after stopping the study drugs. Women and men who cannot have children do not need to use contraception.
排除标准
- •Patients may not be eligible for this study if they:
- •Have an AIDS-related infection or abnormal tissue growth within 1 year of study entry.
- •Are pregnant or breast-feeding.
- •Weigh less than 88 lbs (40 kg).
- •Have taken 3TC or nonnucleoside reverse transcriptase inhibitors (NNRTIs).
- •Have continuously taken for longer than 3 days any of the following prohibited drugs within 14 days before study entry: angiotensin-converting inhibitors, antibiotics, anticonvulsants, antihistamines, antineoplastics, antifungals, anti-inflammatory drugs, benzodiazepines, calcium channel blockers, gastrointestinal agents, systemic glucocorticoids, immunosuppressives, immunomodulators, potassium-sparing diuretics, statins, allopurinol, amiodarone, bromocryptine, danazol, digoxin, methotrexate, metoclopramide, octreotide, ticlopidine, orlistat, pimozide, nefazodone, fluvoxamine, and ergot derivatives.
- •Have taken St. John's wort, grapefruit, or grapefruit juice continuously for longer than 3 days within 14 days before study entry.
- •Are allergic or sensitive to study HAART or cyclosporine.
- •Abuse drugs or alcohol.
- •Have autoimmune disease requiring immunosuppression.
- •Have kidney disease or insufficiency.
- •Have uncontrolled hypertension.
- •Have migraines that require current continuous use of drugs.
- •Have a seizure disorder that requires continuous use of anti-seizure drugs.
- •Have an HLA B-57 haplotype (this gene has been associated with an increased chance for developing an allergic reaction to ABC).