Promoting Infant Health and Nutrition in Sub-Saharan Africa (PROMISE): Safety and Efficacy of Infant Peri-Exposure Prophylaxis (PEP) to Prevent HIV-1 Transmission by Breastfeeding Mechanisms & Safety (M&S)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 562
- 试验地点
- 4
- 主要终点
- HIV seroconversion
研究概览
简要总结
General objective
- To assess the long-term safety and efficacy of one-year infant prophylaxis using lamivudine (3TC) or lopinavir/ritonavir (LPV/r) to prevent post-natal transmission through breastfeeding.
- To investigate the biological mechanisms involved in postnatal HIV transmission.
Specific objectives
- To compare the long-term safety of infant prophylaxis using either 3TC versus LPV/r on child development (growth, somatic and mental health), mortality, adrenal function, liver function, full blood count and mitochondrial toxicity.
- To estimate the final efficacy data of 50 weeks of infant prophylaxis using either LPV/r or 3TC, since some mothers may have resumed breastfeeding after the trial.
- To profile miRNA in breast milk according to maternal HIV status and HIV transmission.
- To determine the influence of maternal milk on infant gut inflammation in an in vitro 3D-intestinal model (CACO-2 cells).
The study population will comprise all ANRS 12174 PROMISE-PEP trial participants who completed the 50 week follow-up and are not HIV infected. An estimate of 881 mother-child pairs from the ANRS 12174 PROMISE- PEP will be recruited.
This study is structured in two parts. The 'clinical & biological safety' component involves a cross sectional survey. A clinical and neuropsychological examination of participants will be conducted. In addition one venous blood sample will be collected to evaluate children HIV status, full blood count, liver & adrenal function and mitochondrial toxicity. Capillary hair follicles will be collected from 100 children in Zambia to study their genome integrity.
The 'mechanisms' component includes biological assays to be conducted on breast milk samples previously collected from HIV infected, transmitting or non-infected mothers enrolled at ANRS 12174 PROMISE-PEP trial.
Primary endpoint: Long term survival, mortality rate, measurements of infant growth (length and weight), somatic and neuropsychological development of the 5 year old children enrolled in the ANRS 12174 PROMISE- PEP trial.
Secondary endpoints: HIV seroconversion since last PROMISE PEP trial visit, full blood count, liver function, adrenal function, serum lactate. Number of mitochondrial DNA copies per cell & percentage of mitochondrial DNA deletion for mitochondrial toxicity. Number of micronuclei & number of Ɣ-tubulin spot per cell to study genomic toxicity.
详细描述
Background Besides optimal efficacy, Prevention of mother-to-child transmission of HIV(PMTCT) strategies must have a very good safety profile (1). Indeed, very large quantities of children will be exposed to these strategies, and the vast majority of them will not eventually be infected. Because in utero HIV exposure followed by one year of antiretroviral treatment (i.e at the time of infant embryogenesis and maturation) may have long-term consequences, such as hampering child development, an evaluation of safety beyond the end of prophylaxis is necessary to get a comprehensive knowledge of the true benefits/risks balance of PMTCT strategies.
A recent review of the state of the art identified several knowledge gaps in the current understanding of Mother To Child Transmission (2). The role of HIV breast milk cell reservoirs in the HIV transmission through breastfeeding is still unclear. The effect of immune factors present in breast milk of HIV infected mothers on HIV population dynamics is also unknown as well as the permeability of infant's gut mucosa and the mechanisms involved on HIV transmission.
The ANRS 12174 randomized controlled trial (ClinicalTrials.gov Identifier: NCT00640263) evaluated 3TC and LPV/r as infant Prep drugs for 50 weeks in HIV uninfected babies at day 7, with monthly follow-up. In addition, breast milk samples were collected four times during follow-up with infant plasma and cell pellets collected at weeks 6, 22 and 38, and infants Dried Blood Spots (DBS) every 3 months. The final results showed that both 3TC and LPV/r achieved very low rates of transmission with an excellent clinical tolerance and no difference between arms in terms of efficacy or safety. In total, 1103 infants completed the final visit.
This study presents a unique opportunity to i) investigate the mechanisms of HIV-1 post-natal transmission, iii) to assess long-term safety of LPV/r and 3TC and ii) to estimate the final efficacy of infant peri-exposure prophylaxis (PreP), since some children were still exposed at the end of the study.
The study will be conducted at the four ANRS 12174 PROMISE-PEP trial sites, namely East London (South Africa), Ouagadougou (Burkina Faso), Lusaka (Zambia) and Mbale (Uganda).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 5 Years 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Having taken part in the ANRS 12174 PROMISE-PEP trial until the final (50 week) visit;
- •Not being infected with HIV during the duration of the ANRS 12174 PROMISE-PEP trial.
排除标准
- •Parent refusal to participate in the study after information about the PROMISE M&S project is given.
结局指标
主要结局
HIV seroconversion
时间窗: From date of last visit in PROMISE PEP study (week 50 of follow-up) until the date of PROMISE-PEP M&S inclusion visit, assessed up to 96 months
Number of children with positive HIV test
次要结局
- Neuro-psychological development(Cross-sectional survey during the inclusion visit)
- Biological disorders(Cross-sectional survey during the inclusion visit)
- Long term survival(From date of last visit in PROMISE PEP study (week 50 of follow-up) until the date of first documented date of death from any cause, assessed up to 96 months)
- Mortality rate(From date of last visit in PROMISE PEP study (week 50 of follow-up) until the date of first documented date of death from any cause, assessed up to 96 months)
- Weight(Cross-sectional survey during the inclusion visit)
- Infant growth(Cross-sectional survey during the inclusion visit)
- Height(Cross-sectional survey during the inclusion visit)