Laboratory Program

The Laboratory Program provides clinical services and conducts molecular virology research for the benefit of people living with HIV.

 

First and foremost, the laboratory performs personal medicine tests that help physicians choose the optimal anti-HIV drug therapy for each individual client. Personalizing HIV treatment results in better outcomes than generalized therapy.

 

The BC-CfE Laboratory primarily performs HIV and Hepatitis C virus (HCV) drug resistance testing. Drug resistance tests monitor genetic changes in an individual’s virus that can affect how well the therapy works. The BC-CfE laboratory also performs HLA-B*57:01 screening for abacavir hypersensitivity. This is a type of genetic medicine test that identifies when a person carries a specific gene that can cause severe side effects to the anti-HIV medication abacavir. The laboratory also performs HIV tropism testing, which can determine whether a class of drugs called co-receptor antagonists are appropriate for use. Finally, the laboratory performs therapeutic drug level monitoring as a research-use-only test. This test is an important tool for investigating drug absorption, treatment adherence, toxicities, and side-effects, where results are used by physicians to understand why some clients may not be responding well to a particular anti-HIV drug. The BC-CfE Laboratory provides these clinical services for nearly all provinces and territories in Canada.


The BC-CfE Laboratory is accredited by the Diagnostic Accreditation Program (DAP) of the College of Physicians and Surgeons of BC to ISO 15189 standards, and by the College of American Pathologists (CAP). The Laboratory is also designated a Specialized HIV Drug Resistance Testing Laboratory by the World Health Organization (WHO) HIV Drug Resistance Network.

Lab Research

The BC-CfE laboratory research team includes individuals with expertise in virology, genomics, chemistry, molecular biology, and bioinformatics.

The laboratory conducts applied and translational research in molecular genetics to better understand the ways in which HIV is able to persist in an individual despite anti-HIV drug therapy. Findings are rapidly translated into clinically relevant tools. The laboratory also conducts research into HIV drug efficacy and resistance, as well as the human and viral factors that influence HIV disease progression.

The BC-CfE laboratory also conducts basic discovery research in HIV biology, including the genetic diversity and evolution of HIV in individuals and populations. A major area of focus is the evolutionary dynamics of HIV persistence in the body, towards the ultimate goal of developing an HIV cure.

BC-CfE laboratory researchers collaborate with scientists and clinicians around the globe. The lab continually develops and transfers new laboratory methods and in-house software to other groups worldwide. The laboratory stays abreast of the many, rapidly changing developments taking place in technology and instrumentation.

The BC-CfE laboratory has received peer-reviewed funding from the Canadian Institutes of Health Research (CIHR), the US National Institutes of Health (NIH), Michael Smith Health Research BC, Genome BC and other funders.

Information on Routine Laboratory Tests:

The ultimate goal of anti-HIV drug therapy is to reduce the amount of HIV in an individual’s blood (viral load) to an ‘undetectable’ level. Anti-HIV drugs work by stopping the virus from reproducing inside the body. These drugs are used in combination and can be effective for a very long time.

What HIV Drugs are available?

There are multiple classes of anti-HIV (antiretroviral) drugs:

  • Nucleoside analogue reverse transcriptase inhibitors (NRTIs) including zidovudine, lamivudine, abacavir, emtricitabine, and tenofovir
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) including nevirapine, etravirine, efavirenz, rilpivirine and doravirine
  • Protease inhibitors including lopinavir, atazanavir and darunavir
  • Integrase inhibitors (INSTIs) including raltegravir, elvitegravir, dolutegravir, bictegravir and cabotegravir
  • Entry inhibitors include fusion inhibitors such as enfuvirtide, attachment inhibitors such as fostemsavir, and CCR5 inhibitors such as maraviroc

How does drug resistance testing work?

The BC-CfE laboratory extracts genetic material from the HIV in a person’s blood and uses sequencing technology (similar to DNA fingerprinting of the virus) to identify drug resistance mutations. Lists of specific mutations associated with drug resistance are available in the scientific literature. The laboratory report shows whether the virus has these mutations, and which anti-HIV drugs are likely to be affected by the mutations. Drug resistance to NRTIs, NNRTIs, PIs and INSTIs is included on the clinical report.

If someone has had routine HIV viral load testing done at St. Paul’s Hospital, drug resistance testing can be done using left-over, stored blood samples from this test. In this case the client does not need to have blood drawn again. The test usually takes about two weeks.

When should drug resistance testing be performed?

Individuals newly diagnosed with HIV should be tested even if treatment will not be started right away. Testing will identify whether the transmitted virus already contained drug resistance mutations. Drug resistance testing should be repeated before switching to different drugs to ensure that the new drugs will be effective.

Testing for drug resistance is especially important if a person is experiencing poor or no response to anti-HIV drugs as indicated by rising viral loads. Test results will help the doctor choose appropriate new drugs for a successful therapy.

Can the likelihood of drug resistance be decreased?

Yes. HIV cannot mutate if it is not reproducing. When anti-HIV drugs are working HIV reproduction is minimal. HIV drugs only work at their best when taken as directed, with no missed pills. This is one key factor in preventing drug resistance.

What is abacavir hypersensitivity, and who is at risk?

Abacavir is a drug used to treat HIV infection, similar to zidovudine (AZT) and lamivudine (3TC). Abacavir is available as a single drug (Ziagen) or in single-pill combinations with other antiretrovirals.

Most people can safely take abacavir; however, a small number of individuals experience a severe side effect known as abacavir hypersensitivity. The most common symptoms are skin rash, fever, nausea, vomiting and diarrhea. About 5% of individuals who take abacavir experience abacavir hypersensitivity. This reaction can be very serious and in some cases cause death.

People who have a specific gene called HLA-B*57:01 are much more likely to experience abacavir hypersensitivity than those who do not. Therefore, individuals with the HLA-B*57:01 gene should not take abacavir. Approximately 5-8% of people with European-, 1-2% of Asian-, and 2% of African ancestry have this gene.

How does HLA-B*57:01 screening for abacavir hypersensitivity work?

A test called HLA-B*57:01 Screening should be ordered before the start of therapy containing abacavir. The test requires drawing a single tube of blood which will be sent to the BC Centre for Excellence in HIV/AIDS laboratory for analysis. The laboratory extracts genetic material from the individual’s blood and uses sequencing technology to identify whether the person has the HLA-B*57:01 gene.

In contrast to other HIV laboratory tests such as viral load, and CD4 count, and HIV drug resistance tests, the results of which can change over time, a person’s HLA-B*57:01 result does not change. This test needs to be done only once.

What do the HLA-B*57:01 abacavir hypersensitivity screening test results mean?

A positive test result means that the person has the HLA-B*57:01 gene and therefore is at higher risk of the abacavir hypersensitivity reaction. This person should not take abacavir. A negative test result means the person does not have the HLA-B*57:01 gene.

Having a negative test result does not guarantee that abacavir hypersensitivity will not develop. It only means the individual is at low risk. You should let your doctors know immediately if you develop a rash, fever or have any of the above symptoms when taking abacavir.

Information on Specialized Laboratory Tests:

Fusion inhibitors (e.g., enfuvirtide, aka Fuzeon or T-20) are a type of drug that doctors may prescribe to people living with HIV, especially when some of the more common anti-HIV drugs are not working.

Fusion inhibitors block HIV from fusing (attaching) to human cells.
What is HIV tropism?

Tropism refers to the way HIV enters cells. The virus enters the human cell by attaching to specific host proteins on its surface. Some types of HIV attach to a protein called CCR5 and others attach to a protein called called CXCR4. “Tropism” refers to which proteins the specific strain of HIV attaches to: HIV strains that attach to CCR5 are called “CCR5-using” while those that attach to CXCR4 are called “CXCR4-using”.

Most HIV infections are caused by CCR5-using virus. However, as HIV reproduces it can sometimes change from a CCR5-using virus to a CXCR4-using virus. As this transition is taking place a person can have both types of virus at the same time (dual tropism). Without testing, there is no way to tell whether a patient has CCR5-using, CXCR4-using, or dual tropic virus.

What is HIV tropism?

If HIV is not able to enter the cell, it cannot replicate. One type of anti-HIV drug works by blocking the CCR5 protein on a person’s cells, preventing CCR5-using strains of HIV from entering the cell. This type of drug is called a “CCR5 antagonist”. Currently, the only drug of this type is maraviroc (Celsentri).

Maraviroc prevents CCR5-using virus from entering the cell, but cannot stop the CXCR4-using virus. This is why it is essential to know which tropism a person’s virus has before initiating treatment with maraviroc. Individuals with dual tropic or CXCR4-using HIV are not good candidates for maraviroc because CXCR4-using virus would continue to replicate. Maraviroc should only be prescribed to individuals who exclusively have CCR5-using HIV.

When should the tropism test be done?

HIV tropism can change as the virus reproduces and mutates over time. If the last tropism test was done too long ago, the test result may not represent the individual’s current virus. Tropism testing should be done just prior to starting maraviroc, and should be repeated if this drug treatment begins to fail.

When should the tropism test be done?

HIV tropism can change as the virus reproduces and mutates over time. If the last tropism test was done too long ago, the test result may not represent the individual’s current virus. Tropism testing should be done just prior to starting maraviroc, and should be repeated if this drug treatment begins to fail.

How does tropism testing work?

The BC-CfE laboratory extracts genetic material from the HIV in an individual’s blood and uses sequencing technology (similar to DNA fingerprinting of the virus) to identify which type of virus the patient has.

There are two different tropism tests, that depend on the person’s current viral load. If the viral load is ≥500 copies/mL, a regular (plasma HIV RNA) HIV Tropism Test should be ordered. If the client has had HIV viral load testing at St. Paul’s Hospital, this type of tropism testing can be done on a stored sample, and no additional blood needs to be drawn.

If the viral load <500 copies/mL, a Proviral HIV DNA Tropism Test should be ordered. This type of tropism testing requires drawing an additional tube of blood.
What are direct-acting antiviral agents (DDAs) for Hepatitis C (HCV) disease?

New therapies have been developed to specifically target the Hepatitis C virus replacing non-specific therapies used in the past. These antiviral agents act directly on viral targets.

Why test for certain mutations in the Hepatitis C virus?

Resistance-associated mutations have been found after treatment, and occasionally in treatment-naive individuals. DAA treatment regimens may need to be modified for persons living with HCV carrying drug resistance mutations.

What causes Hepatitis C virus drug resistance mutations?

It is thought to result from selective pressure from drugs during treatment or genetic variation inherent in the virus itself.

How does this testing help?

The testing is able to detect mutations and/or variations in the Hepatitis C virus that would prevent a drug from being fully effective. With this information, the physician can choose a therapy that the individual’s particular virus will respond to.
What is therapeutic drug monitoring?

When someone takes anti-HIV drugs, the drugs are absorbed into the body’s cells and the virus in the cells is then affected by the drugs. The amount of drug must be high enough to be absorbed by the body’s cells, but not so high that they cause side effects. Therapeutic drug monitoring (TDM) measures whether an individual has too little or too much drug in their system. Not all drugs can be measured using this test, but many of the most common anti-HIV drugs can be (PIs, NNRTIs, INSTIs).

Why is therapeutic drug monitoring done?

If the drug level is not high enough in the body, or the drug is not absorbed well by the body, HIV will continue to replicate. On the other hand, if levels are too high, the drug may cause toxicities or unwanted side effects.

Why do drug levels vary?

Various factors can influence drug levels. Genetic makeup, kidney or liver problems, body size, food intake with medication, and pregnancy are examples. Taking other medications or supplements can also increase or decrease anti-HIV drug levels. If pills are not taken according to schedule or are skipped altogether, this will also have an effect on drug levels.

When should patients receive therapeutic drug monitoring?

Most people do not need Therapeutic drug monitoring (TDM). Nevertheless, it can be helpful if drug treatment is not working, and the failure cannot be explained by drug

What is involved in therapeutic drug monitoring?

There are two types of therapeutic drug monitoring (TDM): timed and untimed.

Timed TDM is offered at the BC-CfE as part of a Research Study approved by the PHC/UBC Research Ethics Board. It requires consultation with a physician at the BC-CfE, and the participant is required to provide written informed consent to participate. Participants will be asked to follow a specific set of instructions. A blood sample will be drawn immediately before taking medication and at specific times afterwards. This is the best method for seeing precisely how much and how quickly the drug is being absorbed. Results will be discussed with the Principal Investigator or co-investigators (who are physicians at the BC-CfE) of the study along with the responsible physician and/or pharmacist.

Untimed TDM is currently a pilot project that can be performed on stored samples from routine viral load testing in British Columbia. As such, untimed TDM does not require any additional blood draws . This type of test, however, only detects whether the drug is present (or not).

Feedback

In order to provide you with the best of care, we would like to know if our laboratory is meeting your needs. We would greatly appreciate your feedback on this brief survey. Please note that all responses are anonymous and encrypted. To participate in this restricted survey, you need a valid access code. If you have been issued an access code, please click on the link below, enter it in the input box and click continue. If you have not been provided with an access code but would like to participate in this survey, please email lab@bccfe.ca for details.

We ask you to not include any information in your answer that could identify you or any of your clients. If you would like to make a comment about a specific incident with our services that could identify you, please get in touch with lab@bccfe.ca about a secure method to collect your personal information.

 

If you would like to provide any additional feedback including concerns, compliments or complaints, please email lab@bccfe.ca.

 

Thank you for your time and invaluable input.

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