A Strategy Study of Immediate Versus Deferred Initiation of Antiretroviral Therapy for AIDS Disease-Free Survival in HIV-Infected Persons Treated for Tuberculosis With CD4 Less Than 250 Cells/mm^3
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 809
- 试验地点
- 39
- 主要终点
- Percent of Participants Who Survived Without AIDS Progression.
研究概览
简要总结
The purpose of this study is to determine the best time to begin anti-HIV treatment in individuals who have HIV and tuberculosis (TB).
Study hypothesis: Immediate antiretroviral therapy (ART), initiated after approximately 2 weeks of TB treatment, will reduce the frequency of other AIDS-defining illnesses and death in HIV-infected participants being treated for TB by at least 40% at week 48 when compared to deferred ART, initiated at after 8-12 weeks of TB treatment.
详细描述
Tuberculosis (TB) is the most important co-infection in the HIV epidemic; the bi-directional relationship between the two diseases is well established. HIV increases the risk for TB acquisition, reactivation, and reinfection, and reduces survival compared to patients with TB alone. In individuals with HIV, TB infection results in reduced survival, increased risk for opportunistic infections, and elevations in HIV replication. Improving the outcome of HIV-infected individuals who develop TB is of high importance. Initiating antiretroviral therapy (ART) shortly after initiating TB treatment may improve outcomes in individuals co-infected with HIV and TB. However, data to support this suggestion were limited before this study began. This study will determine the most appropriate time to initiate ART in HIV-infected individuals who recently initiated treatment for TB.
This study lasted 48 weeks and comprised two steps. At study entry, participants underwent clinical assessment, drug adherence training, and blood collection. In Step 1, participants were randomly assigned to one of two arms. Participants in Arm A initiated ART after approximately 2 weeks of TB treatment. Participants in Arm B deferred ART until after 8 to 12 weeks of TB treatment. In Step 2, Arm B participants initiated ART; Arm A participants did not enter Step 2. ART consisted of efavirenz (EFV) and emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC and TDF could be given as individual agents. Drug substitutions could be made for participants who could not tolerate the specified regimen. Blood collection and clinical assessments occurred at weeks 4, 8, 12, 16, 24, 32, 40, and 48.
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
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-infected.
- •Confirmed or probable TB (more information on the criterion can be found in the protocol).
- •Chest x-ray within 30 days prior to study entry.
- •Receipt of 1-14 cumulative days of rifampin- or other rifamycin-based TB treatment that was initiated within 28 days prior to study entry.
- •CD4 count less than 250 cells/mm^3 within 30 days prior to study entry.
- •Willing to use acceptable methods of contraception while on study drugs and for 6 weeks after stopping these drugs.
- •Able to swallow oral medications.
- •Parent of guardian willing to provide informed consent, if applicable.
- •Karnofsky performance score =>20 at time of study entry.
排除标准
- •ART for longer than 7 cumulative days prior to study entry or treatment for any period of time with one or more antiretrovirals. Participants who have taken ART during pregnancy or for occupational exposure are not excluded.
- •Allergy or sensitivity to any of the study drugs or their formulations.
- •History of multidrug-resistant TB.
- •Receipt of any investigational therapy or chemotherapy within 30 days prior to study entry.
- •Certain medications.
- •Breastfeeding.
研究组 & 干预措施
Immediate ART
The intervention is the strategy of initiating antiretroviral therapy (ART) after approximately 2 weeks of tuberculosis (TB) treatment.
干预措施: Strategy: Immediate ART (Other)
Deferred ART
The intervention is the strategy of initiating ART after 8 to 12 weeks of TB treatment.
干预措施: Strategy: Deferred ART (Other)
结局指标
主要结局
Percent of Participants Who Survived Without AIDS Progression.
时间窗: Through week 48
As this was a study of the strategy of providing antiretroviral therapy (ART) during the initial treatment of TB versus deferring ART until TB was treated for 8-12 weeks, all eligible participants randomized were followed for 48 weeks, whether they started ART as scheduled, whether they started ART at all, or even if the participant did not have TB and discontinued TB treatment. The percent surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
次要结局
- Time to First New AIDS-defining Illness or Death.(Through week 48)
- Percent of Participants With HIV IRIS.(Through week 48)
- Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality(Through week 48)
- Percent of Participants With Confirmed or Probable Tuberculosis (TB) Whose TB Resolved, or Who Required TB Treatment Through the End of Follow-up, or Died, or Were Lost to Follow-up.(Through week 48)
- Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48.(Through week 48)
- Percent of Participants With MTB IRIS.(Through week 48)
- Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression.(Through week 48)
- Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity.(Through week 48)
- Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.(Through week 48)