MICA: Point-of-care viral load testing for HIV patients

Infection with Human Immunodeficiency Virus (HIV) remains one of the greatest challenges to global health. Over 33 million individuals are estimated to be infected worldwide and, without treatment, most will die within 10 years.

The last 15 years has seen great progress in the development of new treatments for HIV. Today, most adults diagnosed with HIV can hope to have a life expectancy close to that they could expect without HIV infection. Over the last 10 years these technological advances have driven a substantial global effort to give access to treatment for all those infected with HIV.

Recent estimates suggest nearly 8 million people are accessing treatment worldwide. Despite this success, there are major challenges remaining to deliver care to those that need it. One of the major challenges is the ability to monitor those on treatment to ensure that their medication is working by measuring the amount of virus circulating in their blood. It is that challenge that this project aims to address.

Monitoring the level of a patient's HIV virus in their blood (or "viral load") currently relies on centralised laboratory services. A rising viral load can suggest the medication is failing and the need to be assessed for a change of treatment. Even if they are well, most patients on treatment will have their "viral load" measured at least twice a year and, more commonly, four times a year. In the highest burden areas of the world, this creates an unsustainable strain on the infrastructure. Even where patients can access treatment and monitoring, centralised services mean patients have to make a return visit for their results. This is often a significant undertaking, particularly in rural areas, and many results are lost or not acted upon.

This project aims to develop a novel method for detecting the HIV virus in a patient's blood. It uses a method suitable for use at the point-of-care (POC), in other words it can be used at the bedside, the clinic or in the community, wherever the patient is. It uses a technology that is ideally suited to resource-poor environments that are poorly served by central laboratories. The technology can operate from a handheld, battery-powered device without the need for a sample to be handled in a laboratory and in a system that can be operated with minimal training producing a rapid result (within 30 minutes) while the patient waits. The use of technology similar to that used in mobile phones will allow a product to be manufactured at scale at a cost that would be affordable in those parts of the world where it is needed the most.

This project is part of a collaborative programme between Departments of Infectious Diseases and Bioengineering at Imperial College and DNA Electronics (DNAe, www.dnae.co.uk), a SME based in West London. The groups currently collaborate to develop point of care diagnostics for infectious diseases based on proprietary technology held by DNAe centred on a point-of-care platform for label-free nucleic acid detection during amplification. The scientific rationale behind this is that nucleic acid chain extension generates protons and thus, in the presence of a matching target, proton release can be detected during amplification using specific probes in close proximity to a pH-sensing microchip (Patent No. WO/2008/107014). The novelty of this technology lies in its reduced cost (no tagging of reagents or optics required), high-volume manufacturability (standard silicon microchips), speed (rate of primer extension), and amenability for use in a laboratory-free environment (all-electrical handheld readout instrument) for same-day results.
The overarching aim of the project is to optimise LAMP-pH assay for use with a handheld pH detection device that can be manufactured cheaply, and at scale, to provide a diagnostic platform for environments without central laboratory support.
The focus of this project is the development of a semi-quantitative assay for HIV-1 viral load as an application for a developed technology platform. LAMP (Loop mediated isothermal amplification) is the chosen method of amplification, an isothermal methodology generating high quantities of nucleic acid with detectable pH change.
Key aspects to this project are (i) to establish an assay able to amplify low level RNA copy numbers (equivalent to <1000 copies/ml blood/serum) (ii) to optimise reaction to produce detectable pH change within 30 mins or sooner (iii) to validate the performance of the assay across reference panels of HIV

The major beneficiaries of this work are patients with HIV (particularly in resource-poor settings), the carers looking after those patients, the health care organisations providing care for patients, policy makers and funders interested in increasing treatment access for patients with HIV, the company developing the technology and those interested in diagnostic development both within the academic and private sectors.

Patients with HIV who don't have access to effective treatment stand to benefit from this work. The benefit will be both direct and indirect. For those who need to travel significant distances to monitor their care, a new rapid test would reduce their need to travel (which may represent a significant barrier to accessing care). It would provide them with a better quality of care and give them more rapid access to second line treatments should they require them. The benefit to carers will vary from setting to setting but, broadly, nurses, doctors or other health care providers will be able to deal more efficiently with patients, gaining data in real time providing a better quality of care to patients. Individual carers will save time in collating and co-ordinating results and ensuring that they are used to improve patient care. These benefits will be felt more broadly in a health care system, particularly if resources are stretched. The reduction in sample handling, transportation, analysis and data will all provide considerable savings in care.

These savings will be able to reduce the costs for delivering care at scale in resource-poor environments which will in turn allow access to treatment for more people who need it. In the current economic climate there is concern that major international donors, whose support is crucial for sustained rollout of treatment for HIV and other diseases, may struggle to fund treatment. It is recognised at the highest levels within UNITAID that there might have been insufficient focus on diagnostics in the roll out of HIV treatment. UNITAIDs new Treatment 2.0 Strategy states "The need for POC [point-of-care] technologies is particularly key for ensuring rapid, reliable diagnostic results outside major urban areas and/or in settings with limited access to centralised laboratory services".

The company involved in the development of the point of care test will benefit commercially from a test that could have a huge global market and high visibility. The proposed test will be one of a number of applications for a platform technology and, as such, could form part of a portfolio of products suitable for different markets.

The virological know-how developed through this project will be published for the benefit of academic and private-sector researchers. The methodologies developed may be of interest to those developing assays and diagnostics in a range of areas, including infectious disease more broadly.