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Understanding Hiv Diagnostics And Lab Tests
- 1. Understanding Diagnostics and Lab Tests in the Management of HIV Disease
- 4. The HIV Life Cycle .. HIV reproduces inside the CD4 + T-cell Hoffmann CJ, Gallant JE. Infect Dis. 2007;33:1-33. Step 1 Viral Entry Step 2 Reverse Transcription Step 4 Transcription and Translation Step 5 Assembly and Budding Step 3 Integration Viral RNA gp 120 CD4 Receptor Co-receptor (CCR5 or CXCR4) New HIV Particle Viral Proteins Viral DNA Nucleus Cell DNA CD4 + T-Cell
- 5. The HIV Life Cycle Hoffmann CJ, Gallant JE. Infect Dis. 2007;33:1-33. Viral RNA gp 120 CD4 Receptor Co-receptor (CCR5 or CXCR4) New HIV Particle Viral Proteins Viral DNA Nucleus Cell DNA CD4 + T-Cell Step 1 Viral Entry Step 2 Reverse Transcription Step 4 Transcription and Translation Step 5 Assembly and Budding Step 3 Integration
- 6. The HIV Life Cycle . .. Hoffmann CJ, Gallant JE. Infect Dis. 2007;33:1-33. Viral RNA gp 120 CD4 Receptor Co-receptor (CCR5 or CXCR4) New HIV Particle Viral Proteins Viral DNA Nucleus Cell DNA CD4 + T-Cell Step 1 Viral Entry Step 2 Reverse Transcription Step 4 Transcription and Translation Step 5 Assembly and Budding Step 3 Integration
- 7. The HIV Life Cycle Hoffmann CJ, Gallant JE. Infect Dis. 2007;33:1-33. Viral RNA gp 120 CD4 Receptor Co-receptor (CCR5 or CXCR4) New HIV Particle Viral Proteins Viral DNA Nucleus Cell DNA CD4 + T-Cell Step 1 Viral Entry Step 2 Reverse Transcription Step 4 Transcription and Translation Step 5 Assembly and Budding Step 3 Integration
- 8. The HIV Life Cycle Hoffmann CJ, Gallant JE. Infect Dis. 2007;33:1-33. Viral RNA gp 120 CD4 Receptor Co-receptor (CCR5 or CXCR4) New HIV Particle Viral Proteins Viral DNA Nucleus Cell DNA CD4 + T-Cell Step 1 Viral Entry Step 2 Reverse Transcription Step 4 Transcription and Translation Step 5 Assembly and Budding Step 3 Integration
- 9. The HIV Life Cycle Viral RNA gp 120 CD4 Receptor Co-receptor (CCR5 or CXCR4) New HIV Particles Viral Proteins Viral DNA Nucleus Cell DNA CD4 + T-Cell .. Hoffmann CJ, Gallant JE. Infect Dis. 2007;33:1-33. Step 1 Viral Entry Step 2 Reverse Transcription Step 4 Transcription and Translation Step 5 Assembly and Budding Step 3 Integration
- 10. Advances in Treatment and Lab Tests Early 1980s Mid 1980s Late 1980s Early 1990s Mid 1990s Late 1990s Early 2000s HAART 2 ART Era Pre-ART Era Today HAART 1 2008
- 11. Monotherapy and dual therapy Protease inhibitors, 1st DHHS treatment guidelines New formulations and combinations to reduce number of pills, 1st fusion inhibitor CCR5 antagonists, integrase inhibitors Effective prophylaxis for life- threatening OIs AZT used to prevent mother-to-child transmission Early 1980s Mid 1980s Late 1980s Early 1990s Mid 1990s Late 1990s Early 2000s HAART 2 ART Era Pre-ART Era Today HAART 1 2008 Advances in Treatment and Lab Tests ART = antiretroviral therapy; AZT = zidovudine; OIs = opportunistic infections; HAART = highly active antiretroviral therapy; DHHS = Department of Health and Human Services. FDA. HIV/AIDS historical time line. Available at: http://www.fda.gov/oashi/aids/miles.html.
- 12. Monotherapy and dual therapy Protease inhibitors, 1st DHHS treatment guidelines New formulations and combinations to reduce number of pills, 1st fusion inhibitor CCR5 antagonists, integrase inhibitors Effective prophylaxis for life- threatening OIs AZT used to prevent mother-to-child transmission Early 1980s Mid 1980s Late 1980s Early 1990s Mid 1990s Late 1990s Early 2000s HAART 2 ART Era Pre-ART Era Today HAART 1 Treatment decisions primarily based on CD4 + T-cell count VL testing HIV isolated, 1st HIV antibody test OraQuick rapid test Genotype and phenotype resistance tests Tropism test, entry inhibitor test, integrase inhibitor test OraSure test Sensitive VL tests (<400, <50) 2008 Advances in Treatment and Lab Tests VL = viral load. FDA. HIV/AIDS historical time line. Available at: http://www.fda.gov/oashi/aids/miles.html.
- 19. Tests That Tell About The Immune System and Response to Treatment 1
- 24. Viral Load Test Name Results Units Reference Range HIV-1 RNA, PCR, 2ND GEN HIV-RNA, PCR LOG COPIES/ML 885.0 H 2.95 H Copies/mL Log copies/mL <50 <1.7 Clinical Laboratory Report Patient Name DOE, JOHN Date Drawn 12/20/06 Date Received 12/20/06 Date of Report 12/22/06 Sex M Client Name / Address MEDICAL CENTER YOUR DOCTOR, MD 123 MAIN STREET ANYTOWN US 10023 Client I.D. Number 78987456 Account Number 12345 Age 33 Ordering Physician SMITH 123094789 Specimen Number 123273 Time Drawn 11:00 AM Patient I.D./SSN 12345/234-56-7890
- 26. Tests for Learning More About The Virus 2
- 38. Tests for Tracking Overall Health 3
- 48. Thank You! MV281830 © 2008 Pfizer Inc. All rights reserved. Printed in USA/January 2008
Editor's Notes
- The workshop objectives are to: Increase awareness of the importance of regular lab testing in the management of HIV disease Discuss how diagnostics/lab tests, approved and in development, may be used in the management of HIV disease Provide an overview of diagnostic tests commonly used by health care providers in the management of HIV disease
- It’s amazing when you think about how much has been learned about HIV and how quickly the science and art of treating HIV are evolving. Advances in medications and lab tests have revolutionized the detection, monitoring, and management of HIV. Understanding the HIV life cycle has helped researchers develop new and improved drugs to fight HIV. At the same time, new and more sophisticated lab tests are being developed. Today we have about 30 drugs available to fight, including 2 new drugs from novel classes just approved in the last few months. There are also combination pills that combine 2 or 3 drugs. These medications are allowing people with HIV to live longer and healthier lives. 1 In the future, with more drugs and diagnostic tests that work in new and different ways, we look forward to promising new approaches to managing HIV. To understand how HIV drugs fight the virus and how lab tests can help manage HIV, we first need to look at how HIV works. Reference 1. US Food and Drug Administration. Drugs used in the treatment of HIV infection. Available at: http://www.fda.gov/oashi/aids/virals.html. Accessed December 7, 2007.
- This life cycle slide shows how HIV attacks a CD4 + T-cell and then makes copies of itself so it can infect other cells. CD4 + T-cells are a type of white blood cell that are an important part of the immune system. The immune system protects your body from germs and diseases. They’re called CD4 + T-cells because CD4 is the name of a primary receptor (entry point) on the cell’s surface. There are 5 main steps in the HIV life cycle. 1 Drugs used to treat HIV prevent the virus from reproducing by stopping it at different points in its life cycle. Most of the approved HIV medicines attack the virus after it has already entered the CD4 + T-cell. Reference 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis . 2007;33:1-33.
- Step 1 – Viral Entry (HIV attaches and enters): When HIV comes into contact with a CD4 + T-cell, a protein on the surface of the virus attaches to the CD4 receptor, or entry point for the cell, and then fuses itself to that cell. 1 Think of the CD4 receptor as a lock and HIV as a key. Viral entry occurs in 3 stages: attachment, binding, and fusion. 2 Attachment is the first stage and occurs when gp120, a protein on the surface of HIV, attaches to the CD4 receptor Binding is the second stage and occurs when HIV binds to 1 of the 2 co-receptors on the cell’s surface, either CCR5 or CXCR4 Fusion is the last stage in viral entry and occurs when the membranes of the virus and the CD4 + T-cell fuse to allow HIV RNA, or genetic material, to enter the cell A few years ago, we saw the arrival of the first fusion inhibitor. It targets the last stage of viral entry by preventing HIV from fusing with the CD4 + T-cell. 3 More recently (August 2007), the first co-receptor antagonist was approved. 4 Co-receptor antagonists target the second stage of viral entry and keep HIV from binding to the CCR5 or CXCR4 co-receptors on the CD4 + T-cell surface. This prevents the virus from entering the cell. 1 References 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis. 2007;33:1-33. 2. Poveda E, Briz V, Qui ñ ones-Mateu M, Soriano V. HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors. AIDS. 2006;20:1359-1367. 3. US Food and Drug Administration. HIV/AIDS historical time line 2000-2006. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007. 4. US Food and Drug Administration. Drugs used in the treatment of HIV infection. Available at: http://www.fda.gov/oashi/aids/virals.html. Accessed December 7, 2007.
- Step 2 – Reverse Transcription: After the virus enters the cell, it needs to instruct the cell to make more HIV particles. The virus uses an enzyme (protein) called reverse transcriptase to translate instructions into a language that the CD4 + T-cell can understand – it translates the virus’ RNA into DNA. 1 The first HIV drugs that were developed for HIV, the NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors), target this step of the virus life cycle. 1 Later, the NNRTIs (nonnucleoside reverse transcriptase inhibitors) were developed to target this same step. 1,2 References 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis. 2007;33:1-33. 2. US Food and Drug Administration. Drugs used in the treatment of HIV infection. Available at: http://www.fda.gov/oashi/aids/virals.html. Accessed December 7, 2007.
- Step 3 – Integration: In this step, the virus takes control of the cell. The newly produced HIV DNA moves to the nucleus, or command center, of the cell, where another enzyme called integrase helps combine the viral DNA with the cell’s DNA. The enzyme cuts the cell’s DNA and inserts, or integrates, a piece of viral DNA. This tells the cell to make more HIV. 1 A new class of drugs called integrase inhibitors targets this step of the virus life cycle. The first integrase inhibitor was recently approved (October 2007). 2 References 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis. 2007;33:1-33. 2. US Food and Drug Administration. Drugs used in the treatment of HIV infection. Available at: http://www.fda.gov/oashi/aids/virals.html. Accessed December 7, 2007.
- Step 4 – Transcription and Translation: After HIV inserts itself into the cell’s DNA, the infected cell is now ready to produce HIV proteins, or pieces that will be used to make new virus particles. 1 Reference 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis . 2007;33:1-33.
- Step 5 – Assembly and Budding: At this step, the HIV proteins produced by the infected cell come together to form new viruses. At first, these proteins are in a form that can’t be used to build more HIV. A viral enzyme called protease cuts up these proteins into active forms. Another type of HIV drug which was developed in the mid-1990s, protease inhibitors, interfere with the protease enzyme and block this step in the viral life cycle. Next, the processed proteins are used to assemble new virus particles. These new viruses then burst or bud out of the host cell’s membrane, and can go on to infect new CD4 + T-cells and repeat the life cycle. 1 Researchers are currently studying drugs that disrupt assembly, maturation, and budding of new HIV particles. 1 Reference 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis . 2007;33:1-33.
- As we’ve just seen, HIV treatment options are evolving as scientists learn more about the virus and develop new drugs and new lab tests. Let’s put these developments on a timeline to give a perspective of where we’ve come from and how the drugs and tests have evolved over time. Speaker note: Roundtable discussion/exercise with handouts. Time: 10 minutes
- Let’s put together what we know: In the early to mid ’80s there were no HIV treatments available. We can call this the Pre-ART era (pre-antiretroviral treatment). At this time, diagnosis of AIDS was being made based on symptoms, other clinical characteristics, and a drop in CD4 + T-cells. In 1987, AZT (zidovudine or Retrovir ® ), the first NRTI, or “nuke,” was approved, followed by other NRTIs and then NNRTIs, sometimes called non-nukes. 1 A period of monotherapy (treatment using only 1 drug) and then dual therapy (treatment with 2 drugs) followed. These approaches provided limited benefit, because HIV soon became resistant to the drugs. Also during the ART era, AZT was first used to prevent mother-to-child transmission of HIV, 2 and effective prophylaxis (prevention) for life-threatening opportunistic infections became available. 1 1995 brought a major breakthrough with the approval of protease inhibitors and the advent of highly active antiretroviral therapy, or HAART. HAART refers to an effective combination regimen of 3 or more HIV drugs. 3 In the early 2000s, new formulations and combinations of medications were approved to reduce the number of pills people have to take. 4 Today, new classes of drugs are available that work in different ways. Many of the drugs that are now in clinical trials or newly approved were developed to address resistance to existing classes of drugs. Drug resistance means that the virus develops mutations that allow it to continue to multiply even though you are taking HIV drugs. When this happens, the medications you are currently taking may stop working (or work less well), and you will probably need to change drugs. Now let’s take a look at lab tests. Retrovir is a registered trademark of Glaxo Smith Kline Inc. References 1. US Food and Drug Administration. HIV/AIDS historical time line 1981-1990. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007. 2. US Food and Drug Administration. HIV/AIDS historical time line 1991-1994. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007. 3. US Food and Drug Administration. HIV/AIDS historical time line 1995-1999. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007. 4. US Food and Drug Administration. HIV/AIDS historical time line 2000-2006. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007.
- Lab tests and their role in HIV treatment have also evolved, just as options for HIV drugs have evolved. In 1984, the cause of AIDS was determined – the virus now known as human immunodeficiency virus, or HIV. 1 In 1985, the first ELISA (enzyme-linked immunosorbent assay) antibody test, a test for HIV infection, was approved by the FDA. 1 This test detects antibodies that the immune system makes when it encounters the virus. From the mid-1980s to the mid-1990s, a test for the amount of CD4 + T-cells in the blood was the main tool used to track health and make treatment decisions. In 1996, the FDA approved the first viral load (VL) test to measure the amount of virus in the body. VL testing—along with CD4 + T-cell count—became a central tool in managing HIV. 2 In the mid-1990s, a branch of the government called the Department of Health and Human Services, or DHHS, published the first edition of its HIV treatment guidelines. 2 In the early-2000s, VL testing became more sensitive. 2 In the year 2004, the government published guidelines for the use of resistance testing, which can tell which drugs will still work against a person’s HIV. 3 Overall, this timeline illustrates that key lab tests became a part of standard medical practice, improved over time, and provided more information about HIV that ultimately contributed to improved health and quality of life. References 1. US Food and Drug Administration. HIV/AIDS historical time line 1981-1990. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007. 2. US Food and Drug Administration. HIV/AIDS historical time line 1995-1999. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007. 3. US Food and Drug Administration. HIV/AIDS historical time line 2000-2006. Available at: http://www.fda.gov/oashi/aids/miles.html. Accessed February 5, 2007.
- Let’s summarize what we have discussed to this point: Understanding the HIV life cycle has enabled researchers to develop new and improved drugs to fight HIV Drugs used to treat HIV prevent the virus from reproducing by stopping it at different points in its life cycle HIV treatment and care options, including new drugs and lab tests, are continuously evolving Today, new classes of drugs are available that work against HIV in different ways
- Let’s focus on lab tests. Lab tests are essential for providing state-of-the-art health care. In fact, everyone needs lab tests, but if you are living with HIV, these tests are one of the most important ways you and your health care provider can monitor your health and make good decisions about treatment. Lab tests look at 3 key areas: Your immune system and response to treatment – how your immune system is working, your response to medications, and the course of HIV disease progression The virus – how well the virus is responding to medication, and specific characteristics of the virus that help determine which drugs might work best for you Your overall health (including sexual health) – how your body systems are functioning, and whether there is a need to treat or prevent other diseases or problems that are commonly seen in people with HIV Monitoring these 3 areas will help you and your health care provider optimize your care by giving you valuable information about 1 : When to start treatment Your response to treatment When to switch treatments Which drugs to use Whether the drugs are causing side effects or toxicities Reference 1. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- Let’s discuss some of the specific tests in each of these categories. Starting with the immune system and response to treatment, there are 2 major tests used to determine how your immune system is working, how the drugs are working, and the course of HIV disease progression. Can anyone tell me what they are? ( Looking for CD4 + T-cell count and VL ) Now for the virus: can someone give me the name of the main test used to tell the specific characteristics of your particular virus, and to help determine which drugs might work best for you? ( Looking for drug resistance test ) Finally, can anyone tell me some of the tests that are used to check your overall health, including sexual health? ( Looking for chemical screen; complete blood count; test for toxoplasmosis; tuberculosis; Pap test for women; STDs, hepatitis A, B, and C; OIs )
- Taking one step back, the starting point for all HIV care is knowing your HIV status. So getting an HIV antibody test like the ELISA and a confirmatory test is important. By knowing your HIV status and getting regular care, you can take advantage of the advances in testing and treatment we’ve been talking about. The big take-home message here is: the earlier you get started, the earlier you can start to control the virus. The next step is to get baseline tests to measure against over time. These are the tests you’ve just mentioned. For people who are newly diagnosed or entering care for the first time, the following tests are recommended by the DHHS Guidelines: CD4 + T-cell count; VL; drug resistance (if VL over 1000); chemical screen; complete blood count or CBC; toxoplasmosis; tuberculosis; Pap test for women; tests for sexually transmitted diseases, especially syphilis; and for hepatitis A, B, and C. 1 We will discuss all of these tests during this presentation. These tests should be performed at baseline, or when you are first diagnosed or start care. Many of them need to be done routinely after that, while others are done less often, depending on individual factors and the recommendations of the health care provider. Reference 1. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- Once you have lab tests done, a report will be sent to your health care provider. It helps if you have a basic understanding of how the results are reported and what they mean. Normal test values are usually given as a range or reference. Lab tests show whether your results are in the normal range. Personal factors such as gender, race/ethnicity, or age can affect normal range, for example: The normal CD4 + T-cell count range is different for children and adults The normal range for hemoglobin, one of the tests in the CBC that checks for anemia, is different for men and women An out-of-range test result may not signal a major problem with your health. Trends in your results over time are more important It’s important to discuss test results with your health care providers. Facilitator note: Use chem screen handout as an example of a standard lab result to illustrate ranges and references.
- Group discussion: Ask audience, “What are some important questions that someone can ask their health care provider about their lab tests in order to help them understand their results?” List responses on flip chart. Summarize discussion by saying, “All of these questions are great and they can be boiled down to 3 key questions”: Why is this test important? How often should I have it done? What do the results mean and how do they affect my health and HIV treatment?
- Now, let’s go into more detail about the tests. We will start by looking at lab tests that check the status of your immune system.
- Two very important tests that we have mentioned for people with HIV are VL and CD4 + T-cell counts. Both are directly related to 2 main goals of HIV treatment, which are 1 : To maintain or increase the CD4 + T-cell count as much as possible for as long as possible To get the VL as low as possible for as long as possible By interfering with the HIV life cycle, drugs help to reduce the number of copies of HIV in the body and increase the number of CD4 + T-cells. VL and CD4 + T-cell count tests are done at diagnosis and about 2 to 8 weeks later. 1 This gives you a baseline, or starting point, to compare when you have these tests done later. After getting baseline tests, VL and CD4 + T-cell counts are generally performed every 3 or 4 months. 1 Let’s take a look at these tests. Reference 1. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- CD4 + T-cell counts measure how many CD4 + T-cells are circulating in the bloodstream. CD4 + T-cells are measured per cubic millimeter (mm 3 ) of blood (approximately 1 drop of blood). Counting the number of CD4 + T-cells is perhaps the most important tool used to assess the overall health of the immune system in people with HIV. The lower the CD4 + T-cell count, the more likely it is that a person will get sick. The normal CD4 + T-cell count is somewhere between 500 and 1500 cells/mm 3,1 The optimal time to initiate therapy in asymptomatic patients with CD4 T-cell count >350 is not well defined and should take into account the potential benefits and risks associated with therapy, comorbidities, and patient readiness and willingness to adhere to long-term treatment 2 If CD4 + T-cell count falls below 350 cells/mm 3 , the guidelines recommend starting treatment 2 Some opportunistic infections can occur once the CD4 + T-cell count falls below 200 cells/mm 3 , while other infections typically occur when the count is below 100, or even 50, cells/mm 3 . 3 For this reason, prophylactic medications to prevent certain infections are started when the CD4 + T-cell count falls below 100 cells/mm 3,3 References 1. Lab Tests Online. CD4 count. Available at: http://www.labtestsonline.org/understanding/analytes/cd4/test.html. Accessed January 24, 2008. 2. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007. 3. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis. 2007;33:1-33.
- CD4 + T-cell count is an important factor in determining when to start HIV treatment. The DHHS guidelines place an important emphasis on when to start treatment 1 : If the CD4 + T-cell count is above 350 cells/mm 3 the risks and benefits of treatment should be taken into consideration Any person with a CD4 + T-cell count below 350 cells/mm 3 should be treated Any pregnant woman, any person with HIV-associated nephropathy (kidney disease), and anyone coinfected with hepatitis B requiring HBV treatment should receive HIV treatment (note that some drugs work against both HBV and HIV) Speak with your health care provider about any changes in your CD4 + T-cell count and how this may affect treatment plans. Reference 1. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- The VL test measures the amount of HIV circulating in your bloodstream. VL is usually reported as copies of HIV in 1 milliliter (mL) of blood. The test counts up to about 1 million copies/mL and down to about 50 copies/mL. 1 In some cases, tests that count down to 400 copies/mL (the older generation of VL tests) are used by health care providers expecting a smaller initial drop in VL. As we mentioned before, the goal of treatment is to reduce the VL to undetectable (<50 for Amplicor assay and <75 for VERSANT). 2 Because these tests measure the amount of virus differently, it’s recommended that the same test and, ideally, the same laboratory be used each time to get consistent results. If a VL test result is said to be undetectable, this does not mean HIV is no longer present in your body or that the virus can no longer be transmitted to somebody else. It just means that the amount of HIV is too small for the test to find. VL may be a consideration in determining when to begin therapy and, is critical for evaluating how well therapy is working. 2 If VL doesn't become undetectable, or becomes detectable again after a period of being undetectable, this is usually a sign that treatment isn’t working effectively and that it might be necessary to change your drug regimen. 2 References 1. Mylonakis E, Paliou M, Rich JD. Plasma viral load testing in the management of HIV infection. Am Fam Physician. 2001;63:483-490. 2. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- This is a sample VL test report. A VL test result might be included with other lab results, or it may be on a separate page. The first two sections include basic information such as patient name, the date blood was drawn, and the doctor’s name. The bottom section includes the test name, the results, and a reference range. This tells you the following important information: Test Name : HIV-1 RNA, PCR, 2nd Gen HIV-1 RNA: HIV-1 is the most common type of HIV in the United States (there is also an HIV-2 in certain parts of Africa, but this is much less common). This test looks for the amount of HIV-1 RNA in your bloodstream, which tells you how fast the virus is reproducing. PCR: This tells you which type of VL test was used. As I said before, there are 2 types of VL tests — PCR and bDNA. Each test measures the virus in a different way, but the results tell you the same thing: the amount of HIV in your bloodstream. It’s important to use just 1 of these tests consistently over time. This report shows that the PCR test was used. 2nd Generation: The first version of the PCR test could accurately detect down to 400 copies of HIV in a milliliter of blood. But as lab tests improved, a second-generation version was developed that could detect down to 50 copies. Result : This is the VL count. On this report it is 885. Units : This tells you the units in which the test was measured, so this is 885 copies of HIV per milliliter of blood. Log copies/mL refers to logarithms, or logs. Logs are often used to express VL results since these numbers can be very large (in the millions). Reference Range : There is no normal range of HIV, since the virus isn’t normally present in the body. The reference range on a VL lab report usually lists the lowest amount of virus that the particular test can detect. As this is the second-generation PCR test, it can detect down to 50 copies.
- Now meet Sam. Sam is a 30-year-old man recently diagnosed with HIV disease. He just received his CD4+ T-cell count and VL test results. Sam is confused and asks his case manager for help in understanding these lab results. Instructions for roundtable discussion/exercise: Pass out handouts for discussion to participants at each table. Ask each table of participants to choose a recorder and a reporter. Give each group 5 to 10 minutes to answer each question in the handout. If you were Sam’s case manager, how would you explain CD4+ T-cell count and VL to Sam? What would you tell Sam is the most important information he needs to know about each test? What questions should Sam ask his health care provider about each test? After 10 minutes, ask each group to share their responses with the larger group. Time: 10 to 15 minutes
- We have reviewed the basic HIV tests for checking the status of your immune system. Next we will have a look at lab tests that provide more information about the characteristics of your virus and how the HIV drugs are working against it in your body.
- Drug resistance means that HIV continues to multiply even though you are taking HIV drugs. This happens because the virus develops mutations as it reproduces, and some of these mutations can make particular drugs stop working. When this happens, your VL usually goes up and your CD4 + T-cell count usually goes down. This may indicate that the medications you are taking are less effective. Resistance tests are blood tests to determine whether your virus is resistant to available HIV drugs. Resistance tests are available to help determine which drug or drugs in your treatment regimen are not working effectively and to help choose more effective drugs. 1 Testing for resistance is now recommended before starting HIV drugs, as many people have a virus that is resistant to 1 or more of the HIV drugs even before they start treatment. Six percent to 16% of people newly diagnosed with HIV are infected with drug resistant strains of HIV. 1 Resistance tests are also crucial for people who are not responding to their HIV therapy. If you have been taking HIV medications and they are not reducing your VL enough, or if your VL goes back up after being undetectable, it is important that you speak to your health care provider. Several studies have demonstrated that using resistance testing can help keep VL undetectable longer. 1 Reference 1. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- There are 2 main types of resistance tests. Genotype tests use HIV from your blood to check the structure, or genetic sequence, of the virus. They look for key mutations associated with resistance to particular drugs. By finding out which mutations are present, it may be possible to figure out which medications to start with and, if necessary, which drugs to switch to. Genotype testing is simpler, faster, and cheaper to perform than phenotype testing. 1 Recommended as first-line resistance test for people who are treatment naïve, or have never been treated Requires more interpretation than phenotype tests, but costs less and is more widely available Phenotype tests test how sensitive the sample of HIV is when exposed to HIV drugs in a test tube. If it only takes a standard amount of the drug to stop viral reproduction, HIV is not resistant to the drug. If higher amounts of the drug are needed to stop HIV from reproducing, HIV is considered to be less sensitive – that is, more resistant – to the drug being tested. 1 Provide more information than genotype tests about which drugs will be effective against your virus, and may be preferred when evaluating treatment-experienced patients Easier to interpret than genotype tests; however, they are more expensive and may be less widely available Partner with your health care provider to determine whether these tests may be right for you. Reference 1. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- After having an undetectable VL for a number of years, Sam’s VL is now detectable. Sam knows about resistance and calls a treatment hotline to ask about resistance tests. Instructions for roundtable discussion/exercise: 1) Pass out handouts for discussion to participants at each table. Ask participants to choose a recorder and a reporter. Give each group 5 to 10 minutes to answer each question in the handout. Questions: If you were the hotline operator who took Sam’s call, how would you explain genotype and phenotype tests to Sam? What would you tell Sam is the most important information he needs to know about each test? What questions should Sam ask his health care provider about each test? After 10 minutes, ask each group to share its responses with the larger group. Time: 15 minutes
- The lab tests we have already discussed are useful because they help individualize treatment. Looking at a particular person’s lab results—including CD4 + T-cell count, VL, and resistance—can help in making decisions that are best for that person. Many lab tests that are regularly used today (such as VL and resistance tests) were first used in research settings such as clinical trials. As these tests were shown to provide valuable information to help manage HIV, they became part of routine care. Just as new drugs are continually being developed to improve care, new lab tests are continually being investigated. Such tests may help to further individualize treatment and improve health outcomes. Some of the new tests include: Tropism test – determines how HIV enters a CD4 + T-cell, information that can help determine which HIV drugs to use Entry inhibitor test – looks at HIV resistance to entry inhibitors Integrase inhibitor test – looks at HIV resistance to integrase inhibitors Let’s take a look at these.
- As we discussed earlier, viral entry is a 3-stage process. The tropism test focuses on the second stage of viral entry, called co-receptor binding. The tropism test is a blood test that determines how HIV enters a CD4 + T-cell. 1 Reference 1. Poveda E, Briz V, Quino ñ es-Mateu M, Soriano V. HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors. AIDS. 2006;20:1359-1367.
- Specifically, the tropism test determines which co-receptor HIV uses to enter CD4 + T-cells. 1 These co-receptors are called CCR5 and CXCR4. If a person’s virus uses the CCR5 co-receptor, it is said to be CCR5-tropic. If it uses the CXCR4 co-receptor, it is said to be CXCR4-tropic. In some cases, a person’s virus uses both co-receptors. This is called dual- or mixed-tropic. 1 The tropism test identifies people with HIV who may benefit from co-receptor blockers (also called CCR5 or CXCR4 antagonists). 1 Before patients are prescribed a CCR5 antagonist they will need to take a tropism test. These drugs inhibit HIV from using the CCR5 to enter a CD4 + T-cell, which prevents HIV from infecting the cell and reproducing. Along with resistance tests (such as genotype and phenotype), the tropism test provides more complete information about your virus and may be helpful in selecting HIV drugs and putting together effective treatment regimens. Work with your health care provider to decide if this option may be right for you. Reference 1. Poveda E, Briz V, Qui ñ ones-Mateu M, Soriano V. HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors. AIDS. 2006;20:1359-1367.
- You and your doctor may consider if a CCR5 antagonist is right for you. According to the DHHS treatment guidelines, a tropism test should be performed whenever the use of a CCR5 antagonist is being considered. The tropism test is designed to identify the tropism of a person’s virus. The test involves drawing a small blood sample, which is centrifuged, frozen, and sent to a laboratory for analysis 1 A VL of >1000 copies/mL is necessary to ensure accurate results Results, which are usually available within 2 weeks, show whether the patient has a virus that is CCR5-tropic, dual/mixed-tropic, or CXCR4-tropic 1 Learning the tropism of an individual’s HIV gives health care providers valuable information that was previously unavailable. They can use this information to create a more individualized treatment regimen, especially for patients who might benefit from a CCR5 antagonist. Reference: 1. Monogram Biosciences. FAQs-patient questions. Available at: http://www.trofileassay.com/FAQ_Patient_Questions. Accessed December 15, 2007.
- Sam is now on his 3rd HIV treatment regimen and has learned that he has multidrug-resistant HIV. His health care provider has recommended a tropism test. Sam is attending a treatment education workshop and asks the facilitator about tropism testing. Instructions for roundtable discussion/exercise: Pass out handouts for discussion to participants at each table. Ask each table of participants to choose a recorder and a reporter. Give each group 5 to 10 minutes to answer each question in the handout. Questions: If you were the facilitator of the treatment education program, how would you explain the tropism test? Under what circumstances might Sam require a tropism test? What would you tell Sam is the most important information he needs to know about the test? What questions should Sam ask his health care provider about the test? After 10 minutes, ask each group to share its responses with the larger group. Time: 15 minutes
- The entry inhibitor assay is a test that assesses resistance to Fuzeon ® (enfuvirtide or T-20). Fuzeon is a fusion inhibitor, a type of entry inhibitor that targets the third step of viral entry. Fuzeon works by binding to a protein on HIV’s surface called gp41. 1 Once it does this, HIV cannot successfully bind with the surface of CD4 + T-cells, and thus cannot infect healthy cells. Since it looks for resistance to Fuzeon, an entry inhibitor test may be used: Before changing a regimen that includes Fuzeon 2 Before adding Fuzeon to an existing regimen if the health care provider suspects that there is preexisting resistance to this drug 2 References 1. Monogram Biosciences. PhenoSense Entry technology. Available at: http://www.monogramhiv.com/assays/hcp/phenoEntryTechnology.aspx. Accessed April 30, 2007. 2. Monogram Biosciences. PhenoSense Entry advanced technology for assessing HIV. Available at: http://www.monogramhiv.com/assays/hcp/phenoEntryAssay.aspx. Accessed April 30, 2007.
- The integrase inhibitor test measures resistance to integrase inhibitors. 1 As we discussed earlier, integrase inhibitors are a class of drugs that fight HIV by blocking an enzyme called integrase that HIV uses to insert its genetic material into the cell’s DNA. 2 Recently, the first integrase inhibitor was approved and other integrase inhibitors are being studied in clinical trials. References 1. Monogram Biosciences. PhenoSense ™ and GeneSeq ™ for integrase inhibitors assays. Available at: http://www.monogrambio.com/416.aspx. Accessed March 20, 2007. 2. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis. 2007;33:1-33.
- Let’s summarize what we have discussed so far. Looking at a particular individual’s lab results—including CD4 + T-cell count, VL, and resistance—can aid in making decisions that are best for that person Just as new drugs are continually being developed to improve care, new lab tests are continually being investigated Such tests may help to further individualize treatment and improve health outcomes Tropism testing is now available which allow health care providers to determine the co-receptor tropism of a patient’s virus The DHHS guidelines recommend tropism testing prior to the initiation of a CCR5 antagonist 1 Reference 1. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- Getting HIV care is only one piece of what a person needs to do to stay well. People with HIV also need to look beyond the virus and take care of the whole person. In addition to HIV-specific care, it’s important to pay attention to well care, which focuses on preventive care. This includes various exams, tests, screenings, and vaccines necessary to maintain good health. HIV health care providers may be able to perform many of these tests, but a person may also need to see other specialists, such as a dentist and an eye doctor. We’ve been focusing on the tests that track the status of the immune system and the virus. Let’s now focus on other tests and exams that are important for people with HIV. As with any medical tests, a person should work with their health care provider to determine whether these tests may be right for them.
- Tracking your overall health will help your health care provider monitor toxicities or other problems associated with HIV and the drugs used to treat it. This can warn your health care provider if you are developing any side effects, infections, or other health problems. Also, as it is now possible, because of improved care, treatments, and lab tests, for people with HIV to live longer, it is important to work with your health care provider to monitor other health conditions (such as heart disease and cancer) that may arise because of aging or other factors. Most of these tests are done at baseline, when starting care, and on a regular basis after that, while others are done less often, the frequency being determined by the health care provider. People should work with their health care provider to determine what would be best for them.
- The chem screen is a group of blood tests that measure a number of important chemicals produced by your body to help it function properly. 1 A chem screen provides important information on the health of your liver, kidneys, heart, and pancreas, and monitors your risk of diabetes. Markers of heart and metabolic health, such as cholesterol and lipids, are also measured. A chem screen can help determine whether another infection or condition is present, or whether you're having side effects caused by the HIV drugs you're taking. The chem screen provides your health care provider with guidance about which HIV drugs to use and which to stop, and whether you need to be treated for other conditions such as high cholesterol, heart disease, or liver or kidney problems. 2 Your health care provider will determine what tests are necessary and how often they should be performed. References 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis. 2007;33:1-33. 2. HIVInSite. Understanding laboratory tests. Available at: http://hivinsite.ucsf.edu/InSite?page=pb-diag-02-00. Accessed January 24, 2008.
- The CBC examines the components of your blood, including red and white blood cells and platelets. 1 This is important because some drugs can cause low red or white blood cell counts, which can lead to anemia or other blood disorders. Your health care provider will determine what tests are necessary and how often they should be performed. Reference 1. HIVInSite. Understanding laboratory tests. Available at: http://hivinsite.ucsf.edu/InSite?page=pb-diag-02-00. Accessed January 24, 2008.
- Many people with HIV are also infected with one of the hepatitis viruses: A, B, or C. Hepatitis often causes mild or no symptoms, so it is important to be tested and, if necessary, treated. 1 If left untreated, hepatitis B and C can lead to severe scarring of the liver, liver failure, and liver cancer. 2 Some research suggests that HIV positive people coinfected with hepatitis C might develop severe liver disease faster, so early testing and treatment is important. 3 If you test negative for hepatitis A and B, you can be vaccinated. Unfortunately, there is no vaccine for hepatitis C. People with HIV, especially those with lower CD4 + T-cell counts, should be tested for the presence of certain opportunistic infections such as tuberculosis and toxoplasmosis. 1 These infections can become very serious if undiagnosed and untreated. There are medicines available to treat and, in some cases, prevent these infections in individuals at risk. Testing for sexually transmitted diseases such as syphilis is also important so that treatment can be prescribed and transmission to sexual partners avoided. 1 Your health care provider will determine what tests are necessary and how often they should be performed. References 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis. 2007;33:1-33. 2. Centers for Disease Control and Prevention. Viral Hepatitis B. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm. Accessed January 24, 2008. 3. US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: Office of AIDS Research Advisory Council, US Dept of Health and Human Services; December 1, 2007. Available at: http://AIDSinfo.nih.gov. Accessed December 15, 2007.
- There are other special tests for women and men. Pap tests for women and anal screening for men are important for preventing cervical and anal cancer. 1 A Pap test is performed during a pelvic exam for women to examine the cervix for abnormal cells. If any abnormalities are detected, the woman is referred for another procedure called a colposcopy. During a colposcopy, a special microscope is used to examine the cervix carefully for abnormal cell growth and tumors in their very early stages. 1 Some health care providers also recommend anal colposcopy to look for abnormal cell growth, including warts and precancerous lesions (dysplasia), inside the anus in both women with a history of cervical dysplasia and men who have sex with men. It is important for women with HIV to see a gynecologist for pelvic exams, annual mammograms for women older than 40, and family planning. Women who are pregnant or planning to get pregnant should receive regular prenatal care from an obstetrician. It’s also recommended that women perform routine breast self-exams. Hormone levels: Testosterone levels are often low in men and women with HIV. This can cause decreased sex drive, fatigue, and depression. Tests for testosterone and other hormones like estrogen are available. For men aged 40 and older, an annual prostate-specific antigen (PSA) blood test to look for prostate cancer is necessary. Reference 1. Hoffmann CJ, Gallant JE. HIV and AIDS. Infect Dis . 2007;33:1-33.
- Many factors can affect test results. To make sure your test results are as accurate as possible, follow the instructions of your health care provider, if there are any, to prepare for the specific test to be performed. Sometimes test results are affected by foods and beverages. That is why you may be asked to fast (not to eat or drink) for several hours, or overnight, before a test. Tell the person collecting your sample if you have not followed these instructions and in what way you deviated. Give your health care provider your complete personal, medical, and family history. Report any medications you are taking at the time of testing, including herbal remedies, because these can affect the results. You may be asked about the amount of alcohol you consume or tobacco products you smoke. It is crucial that you are open and honest with your health care provider. Providing complete, accurate information will help to ensure the reliability of your test results.
- To conclude our program, let’s review. Advances in medications and lab tests have revolutionized the detection, monitoring, and management of HIV Lab tests are essential for getting the most out of HIV treatment With new drugs and diagnostic tests that work in different ways, we look forward to promising new approaches to managing HIV