An Open-label Phase II Pilot Study of Prevention of Perinatal Transmission of HIV-1 Without Nucleoside Reverse Transcriptase Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 23
- 主要终点
- Success rate, defined by plasma viral load (PVL) <50 copies / mL near delivery with DRV/r monotherapy. Failure is defined as PVL > 50 copies / mL and/or change of antiretroviral therapy during pregnancy for PVL ≥ 50 copies / mL.
研究概览
简要总结
The overall goal is to study the feasibility of darunavir/ritonavir (DRV/r) monotherapy as treatment simplification (switch) in pretreated pregnant women, associated with neonatal prophylaxis with nevirapine, constituting a PMTCT strategy without any Nucleoside Reverse Transcriptase Inhibitor (NRTIs) .
详细描述
90 participants will be enrolled and switch to darunavir monotherapy early in pregnancy (before 16 weeks of amenorrhea) in order to reduce exposure to the antiretroviral nucleos(t)ide analogues. The study treatment during the pregnancy is: darunavir 600 mg + ritonavir 100 mg 2 times 24 (DRV/r) monotherapy This regimen will be started after checking the tolerance of DRV/r 600 mg/100 mg twice daily (recommended dosage for pregnancy in French national recommendations) to replace whatever prior antiretrovirals (ARVs) were used, while maintaining the NRTI backbone for 2 weeks. Woman already receiving a triple drug combination with DRV/r will proceed directly to treatment simplification. If clinical tolerance of DRV/r is satisfactory after 2 weeks, nucleos(t)ides will be stopped. In case of intolerance, the treatment will be determined by the investigator but follow-up of the patient will continue.
No zidovudine will be administered at delivery in case of virological control, according to French Guidelines (Morlat Report 2015).
After delivery, the choice of maternal antiretrovial therapy (ART) is left to the discretion of the clinician and patient.
The mothers are followed up monthly until delivery and the last visit is planes at W4-W6 postpartum. Virological efficacy and safety will be assessed monthly.
In neonates, the prophylactic treatment, nevirapine oral solution, will be administrated as soon as possible in the first 12 hours of life and then for 14 days, once a day at a daily dose of 15 mg for a birthweight ≥ 2.5 kg ; 10 mg for a birthweight ≥ 2 kg and < 2.5 kg and 2 mg / kg for a birthweight < 2 kg (WHO Guidelines 2013 - French Guidelines, "Morlat Report" 2015).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant woman, under 15 weeks gestational age at screening
- •Documented Human Immunodeficiency Virus (HIV) HIV-1 infection (serology and/or plasma HIV RNA viral load)
- •Current treatment with at least two ARVs
- •Virological suppression for at least 12 months, defined by a PVL < 50 copies / mL. A blip (transiently ≥ 50 but < 400 copies/mL) will not be considered as an exclusion criterion, if it is followed by 2 successive controls with CV < 50 at least one month before enrollment
- •Plasma viral load < 50 copies/mL at pre-inclusion
- •CD4 ≥ 250 cells/mm3 at pre-inclusion
- •Informed written consent
- •Health care coverage
- •Inclusion criteria for the child :
- •Mother enrolled in the trial
- •Informed written consent by parents or legal guardians
排除标准
- •Infection by HIV-2
- •History of treatment failure and/or resistance with any Protease Inhibitor (PI). Treatment failure is defined by a viral replication (≥ 50 copies/mL) during antiretroviral treatment. An increasing CV due to treatment interruption will not be considered as a failure, providing that the absence of resistance mutations to at least one PI can be confirmed by genotyping.
- •Documented CD4 lymphocyte less than 200/mm3
- •Known intolerance to darunavir or ritonavir
- •Hepatitis B Virus (HBV) co-infection (HBs Ag-positive and/or detectable HBV DNA) on therapy with analogs (tenofovir, emtricitabine, lamivudine)
- •Known resistance of maternal viral strain to darunavir or nevirapine
- •Intended absence (travel abroad, moving ...)
- •Expected delivery in a maternity hospital not participating in the trial
- •Participation in the trial during previous pregnancy
- •Persons under guardianship or deprived of liberty by a judicial or administrative decision
- •Exclusion criteria for the child:
- •Refusal by parent (s) or legal guardian (s)
研究组 & 干预措施
Single Group
Intervention: Darunavir monotherapy darunavir/ritonavir 600 mg/100mg twice day in monotherapy.
干预措施: darunavir monotherapy (Drug)
结局指标
主要结局
Success rate, defined by plasma viral load (PVL) <50 copies / mL near delivery with DRV/r monotherapy. Failure is defined as PVL > 50 copies / mL and/or change of antiretroviral therapy during pregnancy for PVL ≥ 50 copies / mL.
时间窗: At delivery (around 6 months after enrollment in the study).
次要结局
- Plasma viral load (PVL) <50 copies / mL at delivery, Intention-to-treat (ITT) analysis(At delivery (around 6 months after enrollment in the study).)
- Incidence of treatment changes for inefficacy, defined as PVL≥ 50 copies / mL at 2 successive controls.(Every month from Month1 up to the delivery.)
- Incidence of treatment changes for intolerance / toxicity.(Every month from Month1 up to the delivery.)
- Incidence of treatment changes for other reasons.(Every month from Month1 up to the delivery.)
- Factors associated with inefficacy (HIV-1 DNA). Inefficacy is defined as maternal plasma viral load > 50 copies/mL at delivery and/or change of antiretroviral therapy at any time from enrollment through delivery for plasma viral load > 50 copies/mL.(Every month from Month1 up to the delivery.)
- Factors associated with inefficacy (lymphocytes T CD4+ count).(Every month from Month1 up to the delivery.)
- Factors associated with inefficacy (CD4 nadir). Inefficacy is defined as maternal plasma viral load > 50 copies/mL at delivery and/or change of antiretroviral therapy at any time from enrollment through delivery for plasma viral load > 50 copies/mL.(Every month from Month1 up to the delivery.)
- Factors associated with inefficacy (duration of undetectable plasma viral load before pregnancy).(Every month from Month1 up to the delivery.)
- Adverse pregnancy outcomes (preterm birth)(At delivery)
- Adverse pregnancy outcomes (fetal loss)(Every month from Month1 up to the delivery.)
- Adverse pregnancy outcomes (low birth weight)(At delivery)
- Adverse pregnancy outcomes (low Apgar : < 7 at 5 minutes)(At delivery)
- Adverse pregnancy outcomes (congenital malformations)(At delivery)
- Tolerance in children (hematological examinations).(At delivery, Day 3, 15, Month1, 3 and 6)
- Tolerance in children (biochemical examinations).(At delivery, Day 3, 15, Month1, 3 and 6)
- Interruption rate of postnatal nevirapine (NVP) within 2 weeks of life and patterns;(Day 3, Day15)
- Any case of mother to child transmission would be considered a serious adverse event (SAE) and analyzed immediately.(Day 3, Month1, Month 3 and Month 6.)