A Prospective Study Aiming to Determine the Cartography of Virological Reservoir Related to Antiretroviral Concentrations in Chronic HIV-1 Patients Treated With a First Line of Dolutegravir and Associated Nucleoside / Nucleotide Reverse Transcriptase Inhibitors (NRTIs).
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Characterization of the diffusion of dolutegravir and associated backbone (abacavir/lamivudine or tenofovir/emtricitabine) in lymph nodes
研究概览
简要总结
The main objective of the study is to characterize the diffusion of dolutegravir and associated backbone (abacavir/lamivudine or tenofovir/emtricitabine) in HIV-1 chronic patients in the main putative reservoirs, namely inguinal lymph nodes, rectal, fat tissues and sperm.
详细描述
The major obstacle to a functional cure of HIV infection is the persistence of the latent HIV reservoir.
Several arguments suggest the persistence of a residual viral replication in different compartments, despite an effective antiretroviral treatment. This residual viral replication partially comes from pharmacological sanctuaries where the drugs do not largely penetrate. In such sanctuaries a recent report published in Nature has shown that the virus can replicate with less antiviral pressure contributing to continuously replenish the reservoirs. Nevertheless, this study concerned a limited number of patients and only blood and lymph-node samples were collected for viral analysis. Moreover, the drug distribution was estimated based on mathematical hypotheses without drug measure concentration.
The International AIDS Society recommend for most patients an optimal initial regimen containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI)2. The new integrase inhibitor dolutegravir is more and more widely used in combination with nucleoside/nucleotide reverse transcriptase. Indeed, this drug shows a good tolerance and demonstrates a particularly fast inhibition of the viral replication. Moreover, dolutegravir is active against HIV strains that are resistant to the first generation of integrase inhibitors, raltegravir and elvitegravir. However the penetration of dolutegravir in deep compartments has not been fully characterized: the studies comprised a small number of patients and were not able to estimate the distribution in several compartments at the same time for each patient. Moreover the levels of residual viral replication in those compartments during treatment are unknown, making it difficult to evaluate the capacity of this drug and associated backbone to efficiently act against viral reservoirs maintenance.
The aim of the study is to measure simultaneously dolutegravir and nucleoside/nucleotide reverse transcriptase inhibitors in different compartments to obtain cartography of dolutegravir and associated backbone distribution and the spatial dynamics of virus in each patient.
The decision to study dolutegravir and the two associated backbones (abacavir / lamivudine or tenofovir /emtricitabine) was decided as:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Male HIV-1 infected subjects
- •Age > or = 18 years old
- •Currently receiving as first line therapy 7 days a week for at least 18 months with dolutegravir (at 50 mg once a day) and two nucleoside/nucleotide reverse transcriptase inhibitors (abacavir/lamivudine or ,tenofovir/emtricitabine) or
- •Receiving first-line therapy 7 days a week for at least 18 months with dolutegravir (50 mg once daily) + abacavir/lamivudine followed by dual therapy with dolutegravir + lamivudine for at least 6 months; or
- •Receiving first-line therapy 7 days a week for at least 18 months with dolutegravir + tenofovir / emtricitabine followed by dual therapy with dolutegravir + lamivudine for at least 6 months.
- •HIV RNA currently <50 Cp/mL, , and <50 Cp/mL 6 months after treatment initiation and <50 Cp/mL confirmed at 12 months after treatment initiation
- •Normal PT, APTT and platelet count values at screening
- •Written and informed consent signed by the person and the investigator (no later than the day of pre-enrollment and prior to any examination carried out as part of the study (article L1122-1-1 of the Public Health Code)
- •Person affiliated or beneficiary of a social security scheme (article L1121-11 of the Public Health Code) (State Medical Aid or AME is not a social security scheme)
排除标准
- •Single HIV-2 infection
- •Dolutegravir antiretroviral monotherapy
- •Contraindication to biopsy, taking anticoagulant and antiplatelet drugs
- •Hemophilia
- •Symptomatic sexually transmitted infection
- •Being under guardianship or trusteeship mandate for future protection
- •Participation in another research involving the human person, of category 1 or 2,
- •Associated treatments (Carbamazepine, Oxcarbazepine, Phenytoin, Phenobarbital, Rifampicin, St. John's Wort)
研究组 & 干预措施
Single Arm
Single arm composed by 34 HIV-1 infected male subjects
干预措施: Samplings (Other)
结局指标
主要结局
Characterization of the diffusion of dolutegravir and associated backbone (abacavir/lamivudine or tenofovir/emtricitabine) in lymph nodes
时间窗: At Day 0, between T1 (maximum 3 hours after tacking treatments) and T3 (8 hours after taking treatments)
Dosage of the different antiretroviral drugs molecules in lymph nodes
Characterization of the diffusion of dolutegravir and associated backbone (abacavir/lamivudine or tenofovir/emtricitabine) in fat tissues
时间窗: At Day 0, between T1 (maximum 3 hours after tacking treatments) and T3 (8 hours after taking treatments)
Dosage of the different antiretroviral drugs molecules in fat tissues
Characterization of the diffusion of dolutegravir and associated backbone (abacavir/lamivudine or tenofovir/emtricitabine) in rectal tissues
时间窗: At Day 0, T1 (maximum 3 hours after taking treatment)
Dosage of the different antiretroviral drugs molecules in rectal tissues
Characterization of the diffusion of dolutegravir and associated backbone (abacavir/lamivudine or tenofovir/emtricitabine) in sperm
时间窗: At Day 0, At time T0 (before taking treatments)
Dosage of the different antiretroviral drugs molecules in sperm
次要结局
- Description for each compartment of the relationship between exposure to therapeutic combinations and the level of infection / viral replication(At Day 0)
- Study of the spatial dynamics of viral quasi-species In the different reservoirs(At Day 0)
- Characterization of the level of the replication (RNA-HIV) and the level of infection (DNA-HIV) in the reservoirs(At Day 0)
- Study of the mutations of resistance in the integrase gene(At Day 0)