Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya (0-4.5 Month Randomized Controlled Trial)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 140
- 主要终点
- Growth at 18 Months Post-randomization
研究概览
简要总结
Given the high mortality associated with infant HIV-1 and the fact that surrogate markers are poorly predictive of mortality risk,empiric highly active antiretroviral therapy (HAART) initiation is started in infants younger than 12 months. A problem with this approach is that it obligates infants to life-long therapy, which may be associated with cumulative drug toxicity, poor adherence, and treatment failure. Early HAART for prevention of mortality during the first 2 years of life has potential to salvage immune function and alter viral set-point, allowing withdrawal of therapy, perhaps for several years, until subsequent CD4% decline requires it. This untested approach is attractive because it combines the survival benefits of early pediatric HAART therapy with the benefits of antiretroviral deferral.
One hundred and fifty infants who initiated HAART at <13 months of age will be treated with HAART regimen for 24 months after which those who have immune reconstitution and adequate growth (~100) will be randomized to continued versus deferred therapy. Clinical outcomes, growth, and toxicity will be compared in these children to determine if interruption is a safe and beneficial strategy. Follow-up in this studies will be closely monitored by an external Data Safety and Monitoring Board (DSMB).
详细描述
Hypothesis: Deferring antiretroviral therapy in infants who have immune reconstitution and adequate growth following early therapy of primary infection (initiated HAART during primary infection at less than 13 months of age) will not compromise clinical status or growth and may spare antiretroviral toxicity.
Specific Aim/Primary Objective: To compare growth and morbidity in infants (who initiated HAART during primary infection at less than or equal to 13 months of age with subsequently normalized CD4% and growth following 24 months of HAART) randomized to deferred versus continuous therapy and followed for an additional 18 months.
Secondary Aim/Secondary Objective: To determine predictors of non-progression of HIV among the infants, including: age, adherence, HIV-1 specific immune responses, baseline HIV-1 RNA, CD4 percent and immune activation.
Design: Randomized clinical trial involving HIV-1 treatment of infants (<13 months old) for 24 months, followed by randomization and 18 months follow-up of children randomized to continued versus deferred treatment. This trial is unblinded.
Population: HIV-1 infected infants (<13 months) newly initiating HAART and HIV-1 infected infants already receiving HAART who initiated HAART at age <13 months will be enrolled. After 24 months of treatment follow-up, children with CD4% > 25% and normalized growth will be retained in the study and randomized.
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
- — 至 54 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A. Infants newly initiating HAART
- •Less than 13 months of age
- •HIV-1 DNA detection with confirmation (positive on two HIV-1 DNA filter paper tests)
- •Caregiver of infant plans to reside in Nairobi for at least 3 years (reported by caregiver)
- •Caregiver is able to provide sufficient location information
- •B. Infants already receiving HAART
- •Initiated HAART at <13 months of age
- •Records confirming HIV positive status
- •Documentation of CD4% and weight prior to HAART initiation
- •Must be on 1st line drug regimen
- •Eligibility for randomization:
- •Completed 24 months of treatment with HAART
- •Normalized growth: weight for height z-score (WHZ) > -0.5; Child's weight must be above the 5th weight-for-age percentile and the weight curve must not be flat or falling (i.e. cross 2 major percentile lines or more over the past 3 months)
- •CD4% > 25
- •Children who recently initiated or who require anti-tuberculosis treatment at the time of randomization will be ineligible for randomization.
排除标准
- 未提供
研究组 & 干预措施
Continued HAART
After 24 months of treatment with HAART, half the eligible infants will be randomized to continued treatment with HAART for 18 months.
干预措施: HAART (Drug)
结局指标
主要结局
Growth at 18 Months Post-randomization
时间窗: 18 months of post-randomization follow-up
Weight and height will be transformed to the weight-for-age Z-score (i.e., WAZ) and height-for-age Z-score (i.e., HAZ) using World Health Organization Child Growth Standards, taking into account the infant's age and gender.
次要结局
- Morbidity(18 months post-randomization)
研究者
Grace John-Stewart
Professor
University of Washington