Etiology of Treatment Failure in HIV Positive Children and Adolescents on Boosted Protease Inhibitor-based Regimens
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Number of Participants with treatment success described as viral load below 1 000 copies/ml at the end of follow-up.
研究概览
简要总结
Highly active antiretroviral therapy (HAART) transformed a once fatal condition into a chronic, manageable condition. However, it is estimated that 20-40% of patients on 2nd line treatment (2 nucleotide reverse transcriptase inhibitors [NRTIs] and a boosted protease inhibitor [PI]) are failing treatment. Figures are thought to be higher in children and adolescents.
The reason why patients are failing 2nd line treatment is not exactly known. Failure has been previously attributed to poor adherence. However, some literature shows that some patients on boosted PIs achieve and maintain viral suppression despite suboptimal adherence (adherence of 80- 95%). Viral factors, like drug resistance, are also implicated in treatment failure. However, boosted PIs have high genetic barrier to clinically significant mutations. Therefore, a virus would have to harbour multiple PI mutations for the virus to have reduced susceptibility to boosted PI regimens. Pharmacological factors such as suboptimal dosing, impaired absorption and drug interactions may also be responsible for treatment failure.
If sub-optimal adherence is the reason why children are failing 2nd line treatment, then restoring optimal adherence should result in viral suppression, failure of which might mean that other causes are contributing to failure. If resistance is the cause of treatment failure, then this study will provide evidence for advocating for resistance testing and the use of 3rd line antiretroviral drugs. If children with adequate adherence demonstrate inadequate drug levels in their plasma, then this study will provide evidence to advocate for studies to examine reasons for inadequate drug exposure amongst HIV-infected children. These studies are paramount to optimizing dosing algorithms in this population.
This proposed study will help elucidate reasons for treatment failure in HIV-infected children on second line treatment with the aim of ultimately optimizing antiretroviral treatment strategies for this important group.
详细描述
This is a randomized, controlled, interventional study, which will be conducted in 2 phases.
Phase 1
The first phase of the study will include:
- Screening for study eligibility (viral loads and administering eligibility screening form
- Randomisation to study arms (1:1)- random computer generated numbers, sealed in opaque envelopes, clinic nurse keeps the envelopes and produces them sequentially when asked for
- Enrolment- informed consent and assent, 2 questionnaires administered, hair samples collected
- Three months of follow-up
- Post- intervention/control questionnaire administered, viral load and hair samples collected again
- Patients with viral load <1 000 copies/ml from both arms exit study here. Those with viral load > = 1 000 copies/ml from both arms proceed to phase 2
Phase 2
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parents/guardian willing to consent
- •Child willing to provide assent
- •Documented HIV positive antibody or antigen test
- •Child knows their HIV status
- •Aged between 6 and 18 years (that is, from the day of their 6th birthday up to the eve of their 18th birthday)
- •Registered at Harare hospital paediatric opportunistic infections clinic
- •On second line treatment (ATV/r based)
- •Have taken the above named second line treatment for at least 6 complete, consecutive months
- •Has virological and immunological treatment failure as defined by WHO 2012 criteria
排除标准
- •Patients registered at other health centres who have been referred for specialist care at Harare hospital paediatric opportunistic infections clinic
- •On ATV/r as first line treatment
- •Patients who do not want to be followed up at home.
- •On anti-tuberculosis (TB) treatment
研究组 & 干预措施
Intervention
Research assistants visit participants at home, and send SMS texts on scheduled days for 3 months to encourage adherence to ART. Pill charts, visit charts and text charts are completed. this is called modified directly administered anti-retroviral therapy (mDAART). In addition to the intervention, participants receive standard care at their usual clinic which comprises 3 monthly doctor reviews and adherence counseling at each review visit.
干预措施: modified directly administered anti-retroviral therapy (mDAART) (Other)
Control
Participants get usual care at their clinic, which comprises 3 monthly doctor review visits and adherence counseling at each visit.
结局指标
主要结局
Number of Participants with treatment success described as viral load below 1 000 copies/ml at the end of follow-up.
时间窗: 3 months
Participants with viral load \>=1 000 copies/ml will be described as treatment failure and proceed to have genotyping for drug resistance.
次要结局
未报告次要终点
研究者
Tariro Chawana
Dr
University of Zimbabwe