Linking HIV Prevention and Postpartum Care: Safety, Efficacy and Feasibility of Cabotegravir-LA PrEP in a High-Risk Breastfeeding Population in Botswana
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 500
- 试验地点
- 2
- 主要终点
- Adherence to CAB-LA injections
研究概览
简要总结
The goal of this this hybrid safety/implementation study is to evaluate whether using long-acting cabotegravir (CAB-LA) for HIV prevention (PrEP) is acceptable, feasible and safe in post-partum people who are breastfeeding. The main question[s] it aims to answer are:
- Will CAB-LA injections work well as a way to prevent HIV infection in post-partum people?
- Will CAB-LA injections be safe in post-partum people and their infants who will be breastfeeding?
Participants without HIV who are admitted to the maternity ward after having delivered a baby will be offered to start CAB-LA PrEP. Those who choose to participate will receive their first dose (injection) at the maternity ward and their follow up doses (injections) at their local clinic when they come for routine post-partum and pediatric care. Participants and their infants will be followed in the study for 24 months. We will be following how many people come on-time for their CAB-LA injections, how often they keep coming back, and the reasons they continue (or stop) these injections. We will also test people for HIV at all of their visits to see how many people get HIV during the study. We will also measure the levels of the medication in the blood of the post-partum people and their infants (who may be getting some of the CAB-LA in breastmilk) and evaluate to see if their is any impact of CAB-LA on the health of the post-partum person or their infants.
详细描述
This is a hybrid implementation/safety study of long-acting cabotegravir (CAB-LA) as pre-exposure prophylaxis (PrEP) to prevent HIV infection in a post-partum cohort in Botswana where breastfeeding is common. The investigators will enroll 500 women at risk for HIV while they are admitted to the postpartum maternity ward after delivery at government-run health care facilities in Botswana and follow them for 24 months. The study sites will be located in two districts in Botswana, Gaborone and Molepolole.
The first CAB-LA injection will occur generally before discharge from the maternity ward. Follow up injections at 1 month, and then every 2 months, will be administered at clinics where the women and their infants receive routine care (or at research study sites when needed). The investigators will will measure uptake, adherence, persistence and implementation metrics using a mixed methods approach. The investigators will evaluate factors associated with uptake, adherence and persistence using data collected on all participants via questionnaires. The investigators will also conduct in-depth interviews of eligible participants who do not want CAB-LA and also a subset of enrolled participants at enrollment, 7 months and 19 moths. At each visit The investigators will screen for HIV using 4th generation HIV ag/ab point-of care tests and report HIV incidence over 24 months. The investigators will also evaluate safety outcomes, including postpartum depression, weight gain, and infant growth and INSTI resistance in incident HIV infections. Pharmacokinetics of CAB-LA in lactation (women, infants and breastmilk) will be evaluated in 30 mother-infant pairs in a PK substudy. HIV incidence and safety outcomes will be compared with a similar cohort of participants enrolled in a separate observational study in Botswana. This separate study also enrolls at the time of delivery from the same maternity sites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Mother 18 years of age or older and willing and able to provide an informed consent
- •< 14 days after delivery (calendar day of birth = day 0)
- •Negative HIV screening test (conducted at the time of enrollment)
- •Mother <30 years old or has had < 3 prior pregnancies (Gravida 1, 2, or 3 including this pregnancy)
- •Plan to stay and receive postpartum and pediatric care in the Gaborone or Molepolole region for 24 months
排除标准
- •Receiving carbemazapine, phenobarbital, phenytoin, oxycarbazepine, rifampin, rifabutin, rifapentine, systemic dexamethasone (>1 dose oral/IV), or St. John's wort
- •Suspected to have, recently diagnosed with, or on treatment for TB (due to interaction with rifampin)
- •Previous hypersensitivity reaction to CAB or other INSTI
- •Unstable medical or psychiatric condition making it unlikely they will be able to adhere to injections every 8 weeks
- •Plan for pediatric and post-partum care outside the government system (private clinics)
- •Inflammatory skin condition that compromises the safety of the intramuscular injection
- •Weight <35kg
研究组 & 干预措施
CAB-LA PrEP
Following a negative HIV test, long-acting Cabotegravir Injection (CAB-LA) 600mg will be administered as a 3mL intramuscular (IM) injection in the gluteal muscle at enrollment, 1 month, and then every 2 months, for a maximum of 13 injections over 24 months of follow up.
干预措施: Cabotegravir Injection [Apretude] (Drug)
结局指标
主要结局
Adherence to CAB-LA injections
时间窗: 24 months
The % of injection visits attended by participants
HIV Incidence
时间窗: 24 months
The incidence of HIV infections will be calculated as the number of HIV infections infections identified during follow up, per person-year)
Composite Infant Adverse Effects
时间窗: 24 months
The % of infants with any of the following: incident pediatric HIV infections, Z-score \>=2 standard deviations (SD) below norms for length-for-age, weight-for-age or head-circumference-for-age based on WHO growth curves at 24 months
Uptake of CAB-LA injections
时间窗: 24 months
The % of eligible participants accepting CAB-LA PrEP
Persistence of CAB-LA injections
时间窗: 24 months
The % of participants continuing CAB-LA PrEP at 5 months,11 months,17 months and 24 months
Composite Maternal Adverse Effects
时间窗: 24 months
The % of participants with any of the following: grade 2 or higher DAIDS-graded adverse event, obesity (24 month BMI \>30), new onset diabetes and pre-diabetes (HgBA1c \>5.8 or diagnosis during routine care), hypertension (systolic \>140 or diastolic \>90 on 2 separate measurements, or diagnosis during routine care) and prevalence of depression (PHQ-9 score \>9) or diagnosis during routine care
次要结局
- Inadequate infant growth(24 months)
- Maternal Obesity(24 months)
- Maternal Hypertension(24 months)
- Maternal Depression(24 months)
- Median maternal weight change(24 months)
- INSTI resistance among incident HIV infections(24 months)
- Maternal Diabetes(24 months)
- Maternal Cabotegravir Levels(5 months)
- Infant Cabotegravir Levels(5 months)
- Infant HIV infection(24 months)
- Infant microcephaly(24 months)
研究者
Rebecca Zash, MD
Assistant Professor of Medicine
Beth Israel Deaconess Medical Center