HIV & HIV-associated infections
Neglected infectious diseases
Speeding up HIV treatment initiation in infants
The LIFE study is assessing whether the use of new rapid diagnostic tests for HIV leads to quicker and better treatment of infants with HIV.
The study design is based on the need in Mozambique and Tanzania to have policies to test HIV at birth.
Less than half of infants exposed to HIV are tested for HIV, less than half of those tested receive test results, and less than half of those found to be infected receive antiretroviral therapy. The need to send samples away to central facilities for testing is a key barrier to timely diagnosis and initiation of therapy.
Dr Ilesh Jani of the Instituto Nacional de Saúde in Mozambique: “Classical early diagnosis of HIV in exposed infants is done at 4-8 weeks of age. Blood specimens are collected from infants and sent to a small number of distant laboratories, where the diagnosis is done using sophisticated molecular biology technology. In most health systems in sub-Saharan Africa, results are returned many weeks later. This results in anxiety caused by the uncertainty, loss to follow-up of patients, and delay in initiating anti-retroviral treatment. Even when results are returned to patients and anti-retroviral treatment (ART) is initiated, this often takes place months after birth. This long process contributes to substantial morbidity and fails to prevent deaths due to an early peak of mortality faced by HIV-infected infants at 2-3 months of age”.
Dr Ilesh Jani
The LIFE study will fill important evidence gaps. It will reveal whether the use of rapid point-of-care HIV diagnostics at birth increases ART coverage and benefits infant survival. Secondly, whether measurement of virus levels in mothers at delivery leads to the adoption of special measures to prevent mother-to-child transmission; and, thirdly, what the financial and practical implications are of the use of a rapid diagnostic test. The study will, therefore, provide key data for decision makers on the cost-effectiveness and practicalities of implementing the new technology and new models of care.
A new generation of easy-to-use rapid diagnostic tests may overcome these hurdles, as more infants will receive an early diagnosis and start ART. WHO recommends point-of-care testing, but its implementation presents practical challenges and is likely to have significant financial implications.
Dr Jani: “The recent arrival of point-of-care diagnostics, a technology that can be used by non-laboratory specialists at primary health care level, raises the possibility of speeding up the diagnosis of HIV among infants. If used at maternities, point-of-care diagnostics can also diagnose HIV-infection in neonates at birth.”
Project at a glance
Project: LIFE study
Project lead: Dr Ilesh Jani, Instituto Nacional de Saúde, Mozambique
Countries involved: Germany, Mozambique,Portugal, Tanzania, the US
Target population(s): Infants of mothers with HIV
Sample size: 5040 women and their HIV-exposed babies (144 HIV-infected infants)
Year awarded: 2018
EDCTP funding: €3 M
Members of the LIFE consortium carried out a pilot trial in Mozambique, evaluating point-of-care testing administered by nurses. Compared with usual practices, point-of-care testing led to nearly all infants receiving results within 60 days, compared to 12% in the control group, and 90% of HIV-infected babies were put on ART within 60 days, compared to 13% in the control group.
Following up on these encouraging results, the LIFE consortium has begun a larger trial in two countries. The trial will follow infants for 18 months to assess ART initiation rates as well as longer-term impacts on child mortality and illness. The team will also measure virus levels in mothers at delivery, as a way of identifying infants at high risk of mother-to-child transmission.
The LIFE study will take place in 28 health centres in Mozambique and Tanzania. Half of the study sites will implement a newly designed intervention based on point-of-care testing, while the other half will function as controls and will implement the standard of care. Intervention sites will receive a point-of-care technology that can both diagnose HIV in neonates and measure viral load in mothers and neonates. In these sites, all mothers will be tested for viral load at delivery and all exposed infants will be diagnosed for HIV at birth and week 4-8. Newborns found to be HIV-positive will be offered immediate ART. Newborns testing HIV-negative will be offered postnatal prophylaxis guided by maternal HIV viral load.
Dr Jani, the project coordinator of the LIFE study: “What we aim to show with the study is that point-of-care testing for early HIV diagnosis and for viral load testing can be implemented in health system conditions in sub-Saharan Africa and that it leads to better clinical outcomes for HIV-infected infants.”
Dr Jani: “Our consortium includes two African national public health institutes, two European academic centres and one global health institution. This composition enables us to generate evidence that can inform public health policy in our own countries but also globally. The very design of the research questions was based on the need in both Mozambique and Tanzania to have policies for testing for HIV at birth, point-of-care viral load testing for pregnant women and anti-retroviral treatment of neonates. As our study is performed under regular health system conditions, it will also provide useful general evidence on the feasibility of the intervention”.
Women/children in health facilities in Mozambique.
Stop TB/HIV at One:
Efficient diagnosis of HIV and TB
The Stop TB/HIV at One study is assessing technologies to allow diagnosis of HIV and TB in a single visit.
Earlier diagnosis of TB and prompt treatment may prevent most TB-related deaths in people living with HIV.
HIV infections greatly accelerate the progression from latent TB to active TB disease. Globally, around 10% of new TB cases are among people living with HIV, and in 2016, 374,000 people with HIV and TB co-infections died – 86% of them in Africa. TB remains the leading cause of death of people with HIV.
Diagnosis of HIV is relatively straightforward, as simple and affordable point-of-care tests are available. Detection of TB is more challenging; national surveillance programmes are thought to miss a third of new cases. TB can be difficult to detect especially in people living with HIV, which leads to delayed diagnosis and initiation of treatment.
Prof. Luis Cuevas
Rapid detection of TB is essential to ensure rapid treatment initiation, which improves patient outcomes and reduces the risk of disease transmission. Earlier identification of TB and prompt treatment could prevent most TB-related deaths in people with HIV infections. New tests and careful design of testing strategies could provide diagnostic algorithms that are practical and cost-effectively to use in health centres with limited facilities and improve the timely detection of both HIV and TB.
Photo: The laboratory research team at Zankli Research Centre, in Nigeria.
The Stop TB/HIV at One study aims to develop new approaches for diagnosing HIV and TB rapidly and cost-effectively. Current approaches for TB detection are not suitable for rapid and large-scale screening. The project aims to develop new point-of-care diagnostic tools through the evaluation of a range of tools for diagnosing HIV and TB. Based on the performance of these tests, it will then develop new approaches for use of these tests to enable health care workers to detect TB and HIV in the shortest possible time and at the lowest possible cost.
Prof. Cuevas is the project coordinator of the Stop TB/HIV at One study: “Diagnostic tool vary and are used in several ways. Some tests are easier to use than others; some need a good lab while others can be used in the field. And their cost varies enormously. Some tests are geared to identify patients at high risk of TB; these tests need to have high sensitivity. Some tests could be used to exclude patients with a low risk of TB while others focus on confirmation of diagnosis (and thus need to have high specificity), and so on. These complexities led us to conclude that a single test alone cannot be the solution. Combinations of diagnostics selected to suit the health system context could result in more effective diagnostic algorithms to increase access to accurate diagnosis”.
The performance of these new diagnostic algorithms will then be evaluated in real-life settings in Nigeria and Ethiopia. Prof. Cuevas: “We have worked hard to find solutions that are simple and easily implemented. We hope the approaches will help increase access to a quality diagnosis for the majority of the population.”
Project at a glance
Project: Stop TB/HIV at One study
Project lead: Professor Luis Cuevas, Liverpool School of Tropical Medicine, UK
Countries involved: Ethiopia, Moldova, Nigeria, Spain, UK
Target population(s): All age groups
Year funded: 2016
EDCTP funding: €1.4 M
Total project funding: €1.4 M
Photo: Processing samples with Truelab MTB – a first for Nigeria.
Professor Luis Cuevas of the Liverpool School of Tropical Medicine, United Kingdom, briefly explains: “We know TB disproportionally affects poor people with limited access to health services and that current diagnostics have many limitations. For example, smear-microscopy, an old test available in many low-level health centres, misses nearly half of the cases. More sensitive diagnostics need good laboratory infrastructure and for that reason are only available in hospitals or large laboratories distant from most health centres. The lack of diagnostics tests suitable for low-level health centres is thus one of the major challenges for effective disease control. We need to develop new approaches that increase access to accurate diagnostic tests and health services”.
Prof. Cuevas: “We aim to work with national TB control programs to assess the new algorithms at scale and generate evidence that they are effective in increasing case detection and access to quality diagnosis at a low cost. The main tool for TB control is to interrupt transmission. The more cases we can identify early, the lower the transmission in the community. Secondly, we would have demonstrated that the concept of combining diagnostics can be practical, and we will be able to use this approach again with further diagnostics that may become available. In the longer term, we hope we will have contributed to making the diagnosis of TB accessible to all”.
Rapid detection of schistosome infections
The FREEBILY study is accelerating the development of schistosome diagnostics for pregnant women and young children.
We evaluate a rapid, simple, non-invasive diagnostic, so treatment can be based on a positive diagnosis.
Among parasites, schistosomes (flatworms) are second only to malaria in terms of their health and socioeconomic impact. Around 700 million people live in countries where schistosomiasis occurs, and 90% of those requiring treatment live in Africa.
Control of schistosomiasis relies mainly on mass drug administration with praziquantel. As the condition becomes less common, there is an increasing need for accurate diagnostics to support more targeted strategies. Diagnostics could ensure that vulnerable groups, such as pregnant women and young children, are not unnecessarily exposed to praziquantel.
Dr Govert van Dam of the Academisch Ziekenhuis Leiden (LUMC) in The Netherlands: “These vulnerable groups are usually neglected in schistosomiasis control programmes. The standard treatment regularly causes some (transient) side effects, like stomach ache, dizziness, or cramps. So, patients are generally not willing to take the medicine, nor are doctors willing to prescribe it unless patients are positively diagnosed. In the current project, we are evaluating a rapid, simple, non-invasive diagnostic, so treatment can be based on a positive diagnosis”.
Dr Govert van Dam
FREEBILY will provide evidence on the effectiveness and cost-effectiveness of test-and-treat strategies for schistosomiasis in pregnant women and young children, as well as additional data on the UCP-LF test. Although the studies are being conducted in areas of high and low endemicity of schistosome infections in Madagascar and Gabon, the results will be generalisable to other countries affected by schistosomiasis. The trial may lead to improved health care based on test-and-treat schedules for all patient groups. Once implemented in large-scale schistosomiasis control programmes, these tests may have higher cost-efficiency, accuracy, and patient compliance than the current microscopy-based testing.
Diagnostic tests have been developed to detect schistosome infections based on urine samples. The point-of-care test POC-CCA detects intestinal schistosomiasis but has lower sensitivity for urinary schistosomiasis. By contrast, the UCP-LF test is highly sensitive and specific but requires laboratory facilities.
Dr Van Dam: “Current routine testing is based on stool microscopy, which is much more cumbersome and time-consuming to perform. Moreover, it is usually not available in rural mother-child primary healthcare clinics. Blood/serum-based testing is performed in laboratories. It requires sampling of finger-prick or venous blood.”
The FREEBILY project, coordinated by Dr Van Dam, is evaluating the POC-CCA and UCP-LF tests to detect schistosome infections in women and young children in different contexts. One application is the use of the POC-CCA test in routine mother and child clinics, to support ‘test and treat’ strategies. The project also evaluates the use of the UCP-LF test to detect S. haematobium and provide an accurate measure of praziquantel efficacy in a trial of praziquantel use in pregnant women in Gabon.
“One test is a rapid diagnostic test, commercially available, non-invasive and simple to perform. The other test is still in development towards a rapid diagnostic test and needs a modestly equipped laboratory. The former test has shown to have satisfactory accuracy (sensitivity and specificity) for schistosomiasis caused by S. mansoni, while the second test shows even higher, almost absolute accuracy, and can also be applied to other Schistosoma species as well. The non-invasiveness of the sampling and the speed and robustness of the procedure are the main advantages of the tests.“
Project at a glance
Project: FREEBILY study
Project lead: Dr Govert van Dam, Leiden University Medical Centre, the Netherlands
Countries involved: Gabon, Germany, Madagascar, the Netherlands, Spain
Target population(s): Pregnant women, young children
Year funded: 2018
EDCTP funding: €3 M
Total project funding: €3 M
Photo: Laboratory technician Marie Dechenaud from Bernhard-Nocht-Institut für Tropenmedizin (BNITM) trains FREEBILY field staff in Madagascar on how to perform haemoglobin measurements using a point of care HemoCue® device.
Photo: Johanna Griesbaum of Eberhard Karls University (EKUT) guiding Gédéon Prince Manouana, a PhD student from CERMEL, through parasitic diagnostic techniques as part of training at EKUT.
Photo: Performing the UCP-LF CAA assay in the laboratory at CERMEL.
Dr Lisette van Lieshout
Ms Pytsje Hoekstra