| Ultra-fast, accurate identification of HIV 1 (Group M | | | | allow those who think they may have been infected |
| and Group O) RNA, HIV 2 RNA, | | | | to relax and enjoy considerable peace of mind. |
| Hepatitis C Virus RNA and Hepatitis B Virus DNA in | | | | The identification of patients newly infected with HIV |
| human plasma from as early as 7days post exposure. | | | | is important because it presents several interventional |
| Preliminary diagnosis of very early HIV and Hepatitis | | | | opportunities. It allows for very early identification of |
| C disease is now possible at | | | | newly infected HIV positive people which provides |
| 7 days post possible exposure. This time frame was | | | | the opportunity to anticpate and if necessary |
| previously unavailable but utilisation of standard | | | | terminate by the use of anti-retroviral drugs the |
| routine technology in a novel diagnostic style will | | | | seroconversion illness;to mitigate the chances of that |
| facilitate very early diagnosis. | | | | infection being transmitted unknowingly onwards to |
| The technique utilises a fully automated system | | | | another individual; possibly to alter the course of the |
| made by Roche and the testing method uses | | | | HIV illness by allowing a very early intervention to |
| polymerase chain reaction (PCR) or NAT (Nucleic Acid | | | | limit immune system damage should early intervention |
| Amplification) todetect miniscule amounts of viral (and | | | | at the very early stage be proved to be beneficial. |
| the technique can be applied to bacteria) genetic | | | | In the FDA Workshop on Implementation of Nucleic |
| material. | | | | Acid Testing as long ago as 1999, a Dr Busch |
| The technique was invented in the early 1980's by a | | | | identified the well-known phrase, the "window period" |
| Dr Kary Mullis, who later won the Nobel Prize for the | | | | as being of critical importance in identifying and |
| invetion of such an elegant molecular biological | | | | targeting in terms of NAT. |
| technique. | | | | The window period for HIV 1 and Hepatitis C virus |
| Initially, the test was cumbersome and required | | | | has to date depended very largely on the sensitivity |
| intensive well-trained technicians to run it. In addition, | | | | of the HIV 1 and Hepatitis C antibody detection |
| the cost of running the test, partly because of the | | | | devices. |
| numbers of people involved was high. | | | | This was improved on for HIV by the introduction of |
| Automation via the Roche Taq Multiplex device has | | | | parallel screening with HIV 1 p24 antigen which |
| enabled highly sensitive, highly specific, fully | | | | reduces the HIV 1 detection interval by a week or |
| automated testing to be run on human blood with | | | | so. In symptomatic individuals the combination of HIV |
| the detection of HIV-1 and HIV-2 possible from 6 or | | | | 1 and HIV 1 p24 antigen has successfully identified |
| 7 days post exposure; detection of Hepatitis C from | | | | HIV positive individuals at 12 days post infection. |
| 6 or 7 days post exposure and Hepatitis B virus from | | | | Co-infection with Hepatitis C and HIV has presented |
| 20 days post exposure. | | | | a diagnostic conundrum with occasional delayed |
| The technique has had most application so far in | | | | sero-conversion - a group referred to as |
| terms of screening the human blood supply from | | | | "immuno-silent". |
| blood donors and has reduced the numbers of | | | | Studies on blood taken sequentially and regularly from |
| inadvertent contamination with HIV and Hepatitis C | | | | people in the evolving phases of HIV and Hepatitis C |
| virus very considerably. The technique is also | | | | diseases have given valuable information on the |
| employed in organ donation settings where organs to | | | | window period and which markers appear at what |
| be donated are screened for the HIV-1, HIV-2, | | | | stage. Dr Busch coined the phrase "the eclipse period" |
| Hepatitis C and Hepatitis B viruses. | | | | which I think is a very elegant way of describing the |
| Thinking laterally and working with The Doctors | | | | time between physical transfer of infection to a |
| Laboratory ( a major global referral laboratory in | | | | person and the time when current testing |
| London and CPA, UKNEQUAS, WEQAS, ISFG and | | | | methodologies can identify the illnesses. |
| EMON approved for quality, robustness and high | | | | Almost invariably when a person has been exposed |
| standards), we have collaborated to apply the blood | | | | to HIV then by the time they have symptoms they |
| and tissue screening, ultra-high sensitive technique to | | | | are already in a "viraemic" phase where there is lots |
| beginning the diagnostic process for the diseases | | | | of virus detected. |
| identified. | | | | With lots of virus comes lots ofcore viral |
| The process works as follows. We take a measured | | | | proteins-referred to as p24 antigenand so the |
| amount of blood sufficient to run the three NAT | | | | combined HIV-1 and HIV-1 P24 antigen test is virtually |
| tests for HIV-1 and HIV-2; Hepatitis C virus and | | | | always positive in the symptomatic patient. |
| Hepatitis B virus. We can also include syphilis IgG and | | | | So coming back to Dr Busch and his "eclipse phase", |
| IgM within that screen. The test is performed using | | | | this is the time period we are interested in detecting |
| the Roche platform and runs on the "sample in, | | | | and the blood and organ donation services across |
| results out" techniquewhich reduces chances of | | | | Europe and the USA have utilised highly sensitive |
| contamination of product etc to zero. Should a | | | | NAT techniques to identify early infection to halt |
| positive sample be produced the whole specimen is | | | | contamination of the transfusion blood supply and |
| drilled down to identify the virus producing the | | | | transplanted organs. |
| positive result and further confirmatory tests are | | | | Use of Nucleic acid Amplification Testing or PCR will |
| performed. | | | | reduce the window period, currently contained in the |
| The outcome is a highly sensitive, highly accurate | | | | "eclipse phase" as described above, and allow early |
| detection methodology for detection of the identifed | | | | identification of newly infected HIV positive and |
| viruses. The turnaround time is swift, taking a | | | | Hepatitis C positive individuals at 7 days post |
| maximum of 4 days. | | | | infection. Similarly, early identification of hepatitis B will |
| This has great potential in terms of early identification | | | | be possible with reduction of the window period for |
| of newly infected HIV positive patients and also to | | | | this illness to 20 days. |