Description

HIV and its Diagnosis

The fundamentally necessary process of HIV diagnosis is something that can be fraught with difficulty. In various countries, although treatment of HIV can be provided by NGOs, testing can run into the thousands USD for an HIV positive test. This is something rather undesirable considering the average wages in these countries. Furthermore, HIV testing is done via CD4 count and confirmed by the presence of HIV antibodies. However, this testing method necessitates several months after initial infection

ZIKV and Zika Diagnosis

Current methods for testing for the ZIKV virus are as follows: RNA nucleic acid testing, Trioplex Real-time RT-PCR Assay, serologic testing, and Zika MAC ELISA. RNA nucleic acid testing is the least costly, however, it is also the least accurate means of testing as it looks for ZIKV RNA inside urine and negative tests do not rule out the disease. Furthermore, this test must be followed up by other more difficult tests. the ELISA requires cerebrospinal fluid while the other tests can be expensive.

Griffithsin (GRFT)

GRFT is a protien lectin that has broad spectrum glycoprotien binding capacity. In essence, it is something that is sticky. In particular, it sticks to particular glycoprotiens in the protien coating of viral particles. In the case of the HIV virus, it binds to the GP120 glycoprotein of the viral coating. This glycoprotein is specifically indicated the previous image of HIV.

The Design

Our project provides an optimal solution to these problems specifically geared towards developing regions. A rapdid diagnostic test (RDT) using our Griffithsin (GRFT) molecule to bind to the protien coat of viruses enables a much more sensative and accurate testing measure. Furthermore, the GRFT molecule used is a thermostable variant capable of standing up to extremely high temperatures. This ensures a long shelf life and low cost.

The Issue

By 2016, HIV still affected 36.7 million people across the globe. 71% of those people live in sub-Saharan Africa; over half of them do not know they are HIV positive. Although the developed world considers HIV a manageable disease, many sub-Saharan African countries have mortality rates as high as 761 deaths per 100,000. Furthermore, not knowing one’s HIV status causes several problems: spreading the disease further and decreasing life expectancy as well as the quality of life from not receiving treatment. In many of these countries, ARVs are free and readily available through numerous nonprofit organizations. It was found that 86% of people who know they are HIV+ proceed to take ARVs; better diagnostics is needed in order to help decrease the burden of disease caused by HIV. Our goal as a team is to fill this need by creating a test that would allow many of these people who do not know their status to find out.

However, diagnosing HIV is problematic in this region. In Rwanda specifically, an HIV positive test costs on average over $1300 USD. This may not be a lot for those who have health insurance in first world countries; however, the average hourly wage in Rwanda is $0.53/hr USD. In order to pay for a single HIV positive test, a person who works 40 hours a week would need to work for over 1 year consecutively with no other expenses. This is completely unreasonable. The economic factors associated with getting diagnosed are massive and need to be reduced. One way to do this is to create a reliable rapid test that is as affordable as possible.

Another barrier to diagnosis in the region is access to these tests. Current laboratory tests are not only expensive but they are also located in laboratories. The laboratories can be days away on foot from people. Oftentimes, these people cannot afford to go to the clinic because they need time off work and transportation itself is costly, and/or too hard. These machines also require equipment and electricity; things that are uncommon in rural parts of sub-Saharan Africa. Overall, the issue of diagnosis in this region is massive but consists of several key issues.

Another factor that contributes to the overall cost of the tests is the recovery of the protein. To make the downstream recovery easier, a thermo-stable variant of the lectin can be engineered to ensure that it will not denature if the lysate of cells is heated. This makes the overall process much more simple, which means that the production of GRFT becomes more cost effective.

As for Zika, it is a disease that is mostly spread via mosquito but it causes microcephaly and Guillain-Barre Syndrome in infants when in uteri of infected mothers. Both of these neurological diseases are severe and mothers are in a unique situation when pregnant in regions or when recently returned from a trip to a Zika infected country. Zika is a unique case as many of the antibodies individuals produce in response to the infection are cross reactive with tests we have for Dengue and Chikungunya, two very prevalent diseases in the same region as Zika. This is an issue because if a person has ever been infected with either of these diseases, current rapid tests for Zika would be positive, even if the individual has never had Zika. The tests that indisputably determine whether or not a person has Zika are expensive and require very specialized equipment. In the US, there are currently only three labs that are approved to run this test.