Investigating the Optimal Management of Dolutegravir Resistance: an Open-label Randomised Controlled Trial of Maintaining Dolutegravir or Switch to Ritonavir-boosted Darunavir
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 392
- 试验地点
- 9
- 主要终点
- Proportion of participants with HIV-1 RNA of <200 copies/mL at 6 months
研究概览
简要总结
This clinical trial will address the gap in published data on the effect of dolutegravir (DTG)-associated drug-resistant mutations on viral suppression among people remaining on DTG-based antiretroviral therapy. It will also address the gap in the optimal management strategy for this population.
详细描述
BACKGROUND:
The majority of people living with HIV (PLWH) on first-line antiretroviral therapy (ART) in low- and middle-income countries are on dolutegravir (DTG)-containing regimens. Different countries have adopted different approaches in the management of people on DTG-based first-line ART with repeat HIV viral load (VL) of > 1,000 copies/mL after 3 months of enhanced adherence counselling. For example, Kenya recommends a drug resistance test (DRT) to guide on switch and the optimal second-line regimen; Mozambique and Tanzania recommend switch to 2 nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) without drug resistance testing; South Africa does not recommend switch from DTG or DRT for those who are on first-line DTG-containing regimens within the first 2 years of treatment, after which management is guided by possible DRT and expert opinion. The World Health Organization has recognised the role of drug resistance testing (DRT) in a treatment failure algorithm for people living with HIV receiving DTG-based treatment to minimise unnecessary switches from this regimen. The switch to PI has disadvantages including higher cost, higher pill burden, less convenient administration (often should be taken with food), more potential drug-drug interactions, poorer tolerability and more long-term toxicities.
GOAL:
To assess the efficacy and safety of remaining on DTG compared to switching to DRV/r among people failing DTG-based ART with at least one major DTG DRM.
METHODS:
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
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enrolled in the Ndovu cohort study
- •Able and willing to understand and comply with the protocol requirements, instructions and restrictions
- •Able and willing to provide informed consent for the nested clinical trial (assent as appropriate and legal guardian consent if < 18 years)
- •Age ≥ 3 years
- •Most recent HIV-1 RNA ≥ 200 copies/mL
- •At least one major DTG-associated DRM (substitution at codon 66K, 92Q, 118R, 138K/A/T, 140S/A/C, 148H/R/K, 155H or 263K)
排除标准
- •Pregnant or breastfeeding
- •Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs
- •WHO stage 3 or 4 opportunistic infection which would prevent randomisation to either arm (e.g. due to drug interactions or significant liver or renal injury) within 4 weeks prior to RCT screening
- •Investigator opinion that the potential participant should discontinue DTG immediately for clinical reasons
- •Investigator opinion that the potential participant should not switch to DRV/r for clinical reasons
研究组 & 干预措施
Continue on DTG-based Therapy
Participants in this arm will continue their pre-randomization DTG-based ART regimen
干预措施: Dolutegravir Pill (Drug)
Switch to PI-based Therapy
Participants in this arm will be switched to ritonavir-boosted darunavir (DRV/r)-based ART regimen on the day of randomization
干预措施: Darunavir+Ritonavir (Drug)
结局指标
主要结局
Proportion of participants with HIV-1 RNA of <200 copies/mL at 6 months
时间窗: 6 months
The comparative efficacy of switching to a DRV/r-based regimen after confirmed virologic failure and of remaining on DTG-based ART in achieving viral suppression of \<200 copies/mL at 6 months from randomization among participants with ≥1 major DTG-associated DRM
次要结局
- Proportion of participants with HIV-1 RNA of <200 copies/mL at 12 months(12 months)
- Superiority of switch to DRV/r(6 months)
- Viral suppression with cut-off of 50 copies/mL(6 and 12 months)
- Viral suppression with cut-off of 1,000 copies/mL(6 and 12 months)
- Viral suppression by age strata(6 and 12 months)
- Viral suppression by sex at birth(6 and 12 months)
- Incidence of adverse events by study arm(6 and 12 months)
- Association between adherence and suppression(6 months)
- Incidence of drug resistant mutations (DRMs)(6 and 12 months)
- Patterns of accumulated drug resistant mutations (DRMs)(6 and 12 months)
- Drug resistant mutations (DRM) patterns associated with non-suppression(6 and 12 months)
- Predictors of DTG-associated drug resistant mutations (DRMs)(6 and 12 months)
- Viral suppression by pre-enrolment nucleoside reverse transcriptase inhibitor (NRTI)(6 and 12 months)
- Viral suppression by tenofovir disoproxil fumarate versus tenofovir alafenamide(6 and 12 months)
- Change in cluster of differentiation 4 (CD4) Count(6 and 12 months)
- Patient satisfaction as measured using the HIV Treatment Satisfaction Questionnaire - Status version (HIVTSQs) which scores 10 variables on a 7-point likert score ranging from 0 to 6 with a higher score representing a better outcome(6 months)
- Change in patient satisfaction as measured using the HIV Treatment Satisfaction Questionnaire - Change version (HIVTSQc) which scores 10 variables on a 7-point likert score ranging from -3 to +3 with a higher score representing a better outcome(Month 6)
研究者
Loice Achieng Ombajo
Chief Investigator
University of Nairobi