Investigating the Optimal Management of Dolutegravir Resistance: a Multi-country Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 6,600
- 试验地点
- 9
- 主要终点
- Viral suppression rate
研究概览
简要总结
The goal of this study is to address the gap in published data on viral suppression among people meeting the criteria for virologic failure on dolutegravir (DTG)-based ART regimens without a change in regimen. The study will also assess the emergence of DTG-associated drug-resistant mutations and their impact on viral suppression.
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 counseling. 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.
OBJECTIVE:
To assess viral suppression rate following enhanced adherence counseling among people on DTG-based ART who have sustained viraemia (≥ 1,000 copies/mL) after at least six months on ART.
METHODS:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to provide informed consent (assent as appropriate and legal guardian consent if < 18 years)
- •Age ≥ 1 years
- •Documented HIV-1 infection as confirmed by national HIV testing standards at the respective study sites
- •On a DTG-based ART regimen for at least six months
- •Most recent HIV-1 RNA ≥ 1,000 copies/mL within 3 months prior to enrolment, taken after at least 6 months on current ART regimen
排除标准
- •Has switched ART regimen for confirmed or suspected HIV treatment failure while on a PI- or INSTI-based regimen
- •Any reason which, in the investigator's opinion, will significantly prevent the collection of viral load levels such as relocation to another area outside of the trial sites or imminent death
- •Concomitant NNRTI or PI while on DTG
结局指标
主要结局
Viral suppression rate
时间窗: 12 months
Viral suppression rate following enhanced adherence counseling
次要结局
- Time to viral suppression(12 months)
- Viral suppression by age strata(12 months)
- Viral suppression by viral load strata(12 months)
- Viral suppression by sex at birth(12 months)
- Viral suppression by nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)(12 months)
- Durability of suppression(12 to 24 months)
- Incidence of drug resistant mutations (DRMs)(12 months)
- Drug resistant mutations patterns(12 months)
- Predictors of development of dolutegravir (DTG)-associated drug resistant mutations(12 months)
- Time from viraemia to drug resistant mutations(12 months)
研究者
Loice Achieng Ombajo
Chief Investigator
University of Nairobi