The Impact of Co-infections on Inflammation in Patients Commencing Second-line Antiretroviral Therapy. A Sub-study of D²EFT (Dolutegravir and Darunavir Evaluation in Adults Failing Therapy)
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- Change from baseline in IL-6 level at week 48
研究概览
简要总结
i2-D²EFT substudy is an observational cohort nested within the parent D²EFT study (NCT03017872). D²EFT goal is to compare the standard of care second-line antiretroviral therapy in people living with HIV whose first-line non nucleoside reverse transcriptase-based regimen failed, to two simpler regimens. Approximately 1,000 participants will be enrolled in D²EFT.
Commencing a second-line ART is an important moment when the level of inflammation in participants may be elevated due to first-line ART failure; this level of inflammation should then decrease with the commencement of a new second-line treatment and would be expected to normalise by 48 weeks of second-line treatment, if successful.
The investigators propose to study other factors which can influence the decrease of inflammation. The investigators hypothesise that co-infections may play a role in persistent inflammation. The key-infections of interest will be common frequent infections encounter throughout the world: Human Herpes virus 8, Epstein-Barr virus, Cytomegalovirus and Human papillomavirus, tuberculosis, malaria and other key opportunistic infections. Possible changes of level of inflammation (using the serum level of Interleukin 6) in approximately 200 participants of the D²EFT study will be investigated and measured. The hypothesis is that the presence of other infections than HIV may influence the level of inflammation in participants in therapeutic success.
详细描述
i2-D²EFT substudy an observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT (NCT03017872). Participants consenting to D²EFT study will be randomised within the three arms: either ritonavir-boosted darunavir plus two nucleosides or dolutegravir plus two predetermined nucleosides (tenofovir disoproxil fumarate plus lamivudine or emtricitabine) or ritonavir-boosted darunavir plus dolutegravir. Enrolment into the i2-D²EFT substudy is voluntary and optional for participants in D²EFT. Parameters relevant to i2-D²EFT substudy including demographics, arm of randomised ART, HIV history, physical examination, immunological and virological results, episodes of co-infections and adverse events due to any infection or malignancies at required time points will be collected as part of D²EFT study. Substudy specific assessments performed at baseline and at weeks 48 include sample collection for IL-6 dosage plus EBV/CMV/HHV8 testing, and optional anal/cervical HPV screening.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Fulfil the eligibility criteria for D²EFT randomisation;
- •Being able to give a written informed consent for the i2-D²EFT sub-study.
排除标准
- •Unwilling to comply with the i2-D²EFT protocol requirements.
研究组 & 干预措施
SOC
darunavir/ritonavir 800/100mg + 2 NRTIs po od
干预措施: NRTIs (Drug)
SOC
darunavir/ritonavir 800/100mg + 2 NRTIs po od
干预措施: Darunavir (Drug)
SOC
darunavir/ritonavir 800/100mg + 2 NRTIs po od
干预措施: Ritonavir (Drug)
DOL
darunavir/ritonavir 800/100mg + dolutegravir 50mg po od
干预措施: Darunavir (Drug)
DOL
darunavir/ritonavir 800/100mg + dolutegravir 50mg po od
干预措施: Ritonavir (Drug)
DOL
darunavir/ritonavir 800/100mg + dolutegravir 50mg po od
干预措施: Dolutegravir (Drug)
D2N
dolutegravir 50mg + tenofovir + emtricitabine or lamivudine po od
干预措施: NRTIs (Drug)
D2N
dolutegravir 50mg + tenofovir + emtricitabine or lamivudine po od
干预措施: Dolutegravir (Drug)
结局指标
主要结局
Change from baseline in IL-6 level at week 48
时间窗: At week 0 and week 48
To compare the change of a biomarker of inflammation (IL-6) in participants who achieve HIV virological suppression (defined as peripheral blood viral load below 50 copies/mm3 at week 48) across the three study arms according to the presence (or not) of active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).
Change from baseline of presence/absence of active key co-infections at week 48
时间窗: At week 0 and week 48
Active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).
次要结局
- Prevalence of HHV8, EBV and CMV and of cervical and anal HPV(At week 0)
- Occurrence of active HHV8, EBV and CMV(At week 48)
- Change from baseline in rates of detection of cervical and anal HPV infection at week 48(At week 0 and week 48)