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What to Check Under the Hood

Some of the Most Important Tests, and What They Mean

September/October 2007

In many parts of the world, medical providers care for their patients who have HIV/AIDS without the benefit of laboratory tests -- sometimes even the most basic ones. Fortunately, in the United States (and various other countries), medical providers almost always have available to them a wide range of diagnostic tools. Below are some of the most important ones.

1. Complete blood count (CBC). This tells you whether you are anemic (too few red blood cells), neutropenic (too few of the white blood cells called neutrophils that fight bacterial infections) or thrombocytopenic (too few platelets, or thrombocytes, for your blood to clot normally) -- all of which occur commonly in people with HIV. The CBC also gives you something called the "differential," which is an individual count of all the different kinds of white blood cells: neutrophils, monocytes, lymphocytes, basophils, and eosinophils. It is also crucial to determining your total CD4 (T4, T helper) cell count, a critical measure of immune function.

2. CD4 cell count. The FACS (not "fax," although pronounced the same way) or Fluorescence Activated Cell Sorter machine identifies CD4 cells and directly measures what their proportion (percent) is of all your lymphocytes (white blood cells) when your blood was drawn. So, the CD4 percent is what the machine actually measures, and the total (or "absolute") CD4 cell count is derived from multiplying the percentage of CD4 by the total lymphocyte count. That is why the differential (see above) from the CBC is necessary -- in order to obtain your CD4 cell count.

Over time, the CD4 percent is a more stable measure of your immune system function because the total CD4 count is influenced by your white blood cell count at the moment your blood was drawn, a number that varies constantly. Nonetheless, by habit and tradition, health care providers have used the total CD4 cell count for key decisions, such as starting HIV meds or preventive therapy for opportunistic infections, like PCP (Pneumocystis pneumonia).

3. HIV RNA PCR (HIV ribonucleic acid polymerase chain reaction), or "viral load." This key test tells us how much virus is in a millilter (abbreviation: ml) of your blood, one-fifth of a teaspoon. Note that it does not tell us how much HIV is in your entire body, where most of the virus is -- in tissues, such as your lymph glands (lymph nodes). Even though this test uses a tiny quantity of blood, it has proven to be a very good indicator of response to antiretroviral therapy.

There are two versions of the most commonly used test, the Roche assay, and both have established cut-off values for the upper limit of how much virus can be detected and the lower limit, which is referred to as "undetectable" virus. Note that "undetectable" means the amount of HIV is less than the technical ability of the test to detect it and does not mean that HIV is not present.

The Amplicor version of the viral load assay has a low end cut-off of "less than 400 copies/ml" of HIV RNA/ml and an upper limit of "greater than 750,000 copies/ml." The Ultrasensitive test has a low end cut-off of "less than 50 copies of HIV RNA/ml" and an upper limit of "greater than 75,000 copies/ml." The significance of the difference between these two tests is that the Amplicor test is more accurate at higher viral loads and the Ultrasensitive test is more accurate at the low end of viral loads.

It is useful to do the Amplicor test when someone is first evaluated for HIV disease because it is valuable to know before starting treatment if the viral load is in the thousands, hundreds of thousands, or millions. Once someone is on HIV treatment and is doing well, it is more useful to use the Ultrasensitive test, given that the goal is to get the viral load as low as possible and this test is able to detect lower levels of virus in the blood.

There are other types of viral load tests, such as the branched DNA (bDNA) assay, that are sometimes used. There are various technologies but the measurement principles, with cut-offs for the upper and lower limits, are similar to what is described for the RNA PCR tests above.

4. Serum Chemistries -- liver and kidney function tests.

Liver Function Tests (LFTs): These tests measure some key functions of the liver, a complex organ that does many important tasks in the body. The liver manufactures proteins that are essential to blood-clotting and to keeping fluid in your bloodstream instead of leaking out into your tissues and causing swelling (edema). The liver breaks down most environmental poisons (toxins) and drugs to rid the body of them. It also forms bile, which is important for digestion.

Amino aspartate transaminase (AST, formerly SGOT) and alanine aspartate transaminase (ALT, formerly SGPT) are key enzymes that indicate how well liver cells (hepatocytes) are functioning. The levels of an enzyme called alkaline phosphatase and a protein by-product called bilirubin indicate how well the production and excretion of bile is going. Albumin, a protein made in the liver, is critical for keeping fluid in the bloodstream and is an overall measure of nutritional status.

Liver function can be damaged by alcohol abuse, environmental toxins (including street drugs), viral infection of the liver (viral hepatitis) and a long list of diseases. Since people with HIV sometimes also have chronic hepatitis B or C, drink too much, or experience liver damage (hepatotoxicity) from medications, LFTs are important to monitor.

What to Check Under the Hood

Kidney (renal) function tests: These tests measure how well your kidneys are doing their primary job, which is to rid the body of protein waste (blood urea nitrogen, or BUN) and regulate blood volume by filtering out the waste and extra water to form urine. The two main kidney function tests look at the level of waste as a way to measure how efficiently your kidneys are operating. These tests can provide clues that someone might have HIV-associated nephropathy (HIVAN) or kidney malfunction due to other causes, such as dehydration or drug toxicity.

Since some drugs are excreted from the body by the kidneys, dose adjustments need to be made when a person develops altered kidney function. Awareness of kidney dysfunction is also important when selecting an ARV regimen because some medications, like Viread, are not preferred for someone with underlying kidney disease.

Kidney function should be checked when someone enters HIV care. Thereafter, people at high risk of developing kidney disease (primarily African Americans and diabetics or people with a family history of diabetes) should have their kidney function checked at regular intervals. Routine checks are also recommended for people on ARV therapy.

5. Syphilis blood test. Syphilis, like HIV, is a sexually transmitted infection that may have no symptoms at all. If left untreated, it can cause -- years later -- significant disease and death due to damage to blood vessels and the brain.

There are a number of blood tests for syphilis (RPR, FTA, syphilis IgG), but the type of test is less important than the fact that everyone with HIV should have one upon entering HIV care and women who become pregnant should have one. After that, screening depends on risk -- people who are at higher risk of exposure through unprotected sex, especially with multiple partners, may need to be screened regularly. Several outbreaks around the country among men who have sex with men have occurred over the past several years. Sex workers, incarcerated individuals, and people with other sexually transmitted infections are also at high risk.

6. Tests for viral hepatitis. Many HIV-positive people are also infected ("co-infected") with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV). It is very important to find this out because, if left untreated, both conditions can ultimately lead to severe scarring of the liver (cirrhosis), liver failure, and liver cancer (hepatocellular carcinoma, or HCC for short).

Some HIV medicines are active against hepatitis B, so it is important to craft an ARV regimen that will adequately treat both HIV and HBV at the same time. Hepatitis C currently requires treatment with two drugs that do not control HIV, and this therapy can be pretty challenging. However, depending on virus type and other factors, treatment can be very effective.

In addition to HBV and HCV, it is also important to test your blood for proteins that are protective (called antibodies) to hepatitis A (HAV). There is no chronic form of hepatitis A, but if you already have chronic liver disease from hepatitis B or C, you can get much sicker from hepatitis A than someone who doesn’t have HBV or HCV because you already have some liver damage. Since there are vaccines available for hepatitis A and B (but not, unfortunately, for hepatitis C), these should be offered to every HIV-positive person whose blood tests show no prior exposure to these viruses.

7. Resistance tests (genotype and phenotype). These tests tell us whether your virus is resistant to certain HIV drugs (in other words, the medication is not effective against your virus). Testing for transmitted resistance is now recommended before starting HIV meds, as up to 16% of people have a virus that is resistant to one or more antiretrovirals. These tests are also crucial for people who are not responding to their HIV therapy.

Both genotypes and phenotypes are done on a blood sample. Genotypes, which are simpler, faster, and cheaper to perform, identify changes in particular viral genes that are associated with reduced or no response to specific drugs. Phenotypes, which are more complicated, time-consuming, and expensive to perform, test how well your HIV grows in the presence of different concentrations of HIV drugs.

Genotypes may be more than adequate for early resistance because they look at how much resistance the virus has compared to virus with no resistance; phenotypes have some advantages for people with extensive resistance because they can indicate how well the virus responds to individual drugs. The phenotype results can be especially useful when there are no"new" drugs available to someone and the only option is a "salvage" regimen of drugs to which the virus is still susceptible.

In the most difficult cases, both tests add information of value. Cost can limit the availability of these tests, especially the phenotype.

8. Serum lipids. Diet, exercise, cigarettes and your genetic heritage (the genes you inherited from your parents and ancestors) all influence your risk for heart disease. Since we now expect HIV-positive people to live a long time, we have to pay attention to the fact that both HIV itself and some of the medications used to treat it have been associated with abnormal lipid levels (cholesterol and triglycerides, which are fats in the blood). This makes it important to obtain fasting lipids when you first enter HIV care, and to have them repeated at least once a year. Repeating them more often will depend on whether they are normal or not to begin with and what other heart disease risks you have -- are you overweight? Do you smoke? Do you have diabetes or high blood pressure? Do you exercise? Do you have a family history of high cholesterol or heart disease?

To be accurate, lipid testing must be done in the "fasted" state -- no food (or drink, except water or diet soda or plain tea or black coffee -- any drink without calories) for a minimum of eight hours, ideally 10 to 12. Fasting lipids include four separate measurements of different forms of fats that circulate in your blood: total cholesterol, high-density lipoprotein (HDL, or "good cholesterol"), low-density lipoprotein (LDL, or "bad cholesterol"), and triglycerides.

High levels of HDL protect you against heart disease caused by clogged arteries in your heart (atherosclerotic heart disease). Unfortunately, high levels of the other fats are associated with an increased risk for heart disease. Lipid levels can be lowered with lifestyle changes, but some people may also have to take lipid-lowering drugs in addition to a diet change and other interventions.

9. Pap smear. A Pap smear involves scraping cells from the cervix or anus (usually with a tiny cotton swab), preparing them on a slide, and viewing them through a microscope. Every HIV-negative woman should be screened once a year for cell changes on the cervix that could lead to cervical cancer. Depending on CD4 count and other factors, women who are HIV-positive should be screened twice a year (every six months) for cervical cancer.

Cervical cancer is caused by infection with certain strains of human papillomavirus (HPV). Cervical cancer is a real threat to HIV-positive women, especially at lower CD4 counts, and became part of the case definition of AIDS in 1993. If caught early, it can be cured.

Anal Pap smears are still not standard of care due to limitations of the test and because an expert is needed to accurately analyze the results. The wealth of data that exists for cervical Pap smears does not exist for anal Paps, so questions remain about its reliability and predictability as a screening tool. In some centers, anal Paps have been an effective way to screen for anal carcinoma, but many centers lack health care providers and pathologists (the doctors who interpret Pap smears) who can perform this test reliably.

This test was developed initially for men who have sex with men, thought to be susceptible to anal carcinoma because of sexually transmitted HPV infection. However, women can also benefit from such a test, even if they have not had anal intercourse.

10. Screening tests for cancer. Now that HIV-positive people have the prospect of living out a normal lifespan, it is important to provide cancer-screening tests because most cancers are age-related. Also, there is some evidence that people who are HIV-positive may be at higher risk for a broader range of cancers than the ones that have long been HIV-associated, like Kaposi’s sarcoma and B cell lymphoma.

The guidelines for performing these screening tests are the same as those for HIV-negative individuals.

  • For men aged 40 and older: an annual prostate-specific antigen (PSA) blood test to look for prostate cancer
  • For women aged 40 and older: a baseline mammogram (type of x-ray) to detect breast cancer, with subsequent mammograms based on age and family history
  • For all people aged 50 and older: a baseline and then subsequent colonoscopy to detect colon cancer
  • For smokers: QUIT! A chest X-ray may be prudent for smokers, but there is no clear interval for subsequent screening.

Judith Feinberg, M.D., is a clinician and Professor of Medicine at the University of Cincinnati, where she is also the Director of the AIDS Clinical Trials Unit. Dr. Feinberg is an American Academy of HIV Medicine (AAHIVM)-credentialed HIV Specialist. Taken from Positively Aware Special Issue Fall 2006.

Additional Tests, When a Closer Inspection Is Warranted

  1. Testosterone level. Among other key functions, testosterone is the hormone that drives sexual interest (libido) in both men and women, though normal levels for women are much lower than for men. Symptoms of low testosterone (hypogonadism) in men include: depression, lack of energy, reduced muscle mass, and decreased sex drive or arousal. Much less is known about women and testosterone, but low testosterone levels in women also cause decreased sex drive.

    Hypogonadism seems to be common in HIV-positive men, though it is not known why. Testosterone levels in men normally decline with age, so the level has to be interpreted with your age in mind.

    Testosterone replacement can be done by injection every few weeks or by gels or patches that are applied to the skin every morning. It is difficult to replace testosterone in women because the amount needed is so small, and current doses of various testosterone preparations are geared for treating men.

  2. Thyroid hormone level. Low levels of thyroid hormone (hypothyroidism) are reasonably common in women -- HIV-positive or not. Low thyroid levels can cause weight gain, lack of energy, depression, and skin changes. A thyroid stimulating hormone (TSH) level can screen for an underactive, as well as overactive, thyroid gland. Both underactive and overactive thyroid conditions can be treated.
  3. DEXA (dual X-ray absorptometry) scan. This scan tells us about the composition of the various body compartments -- bone, fat, muscle -- and is particularly useful in determining whether you have lost a modest amount (osteopenia) or too much (osteoporosis) of your bone mineral content. Osteopenia and osteoporosis weaken your bones and make them prone to breaking (fractures).

    Bone mineral loss can occur in men with low testosterone levels and women who have stopped having periods (menopause). It can also run in families. This problem can largely be avoided with a good intake of calcium (at least 500 mg per day in dairy foods and leafy greens or as a supplement) and vitamin D (from exposure to sunshine, in fortified milk, or as a daily supplement).

    It is important to do the kind of exercise that makes your muscles tug on your bones, such as resistance exercises that use weights or elastic bands. Walking briskly several times a week is also helpful because you are bearing your own weight, which helps keep your bones strong. In addition to calcium, vitamin D, and exercise, you can treat severe bone mineral loss with a medication you take once a week or once a month to help reverse bone loss.

Note: DEXA scans can also measure how much fat you have inside your body (visceral fat) and under your skin (subcutaneous fat), although this is more of a tool in studies of fat gain and loss (lipodystrophy) than a test used in the clinic to help with treatment of your HIV disease.

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This article was provided by Positively Aware. It is a part of the publication Positively Aware. Visit Positively Aware's website to find out more about the publication.
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