Testing…testing…one, two, three

When you visit your HIV clinic, they will be measuring a lot more than just your CD4 count and viral load. What else are they checking and how does it matter? Guest writer David McLay explains.

Your doctor scans the list of indecipherable acronyms, quickly checking the boxes beside some and skipping over others. She hands the sheet to you and says “You can have some blood taken for the usual tests. Any questions?”

You say “No,” but maybe you think to yourself, “Yes!” What are these tests? What do they measure? What’s a good result and what’s a worrying one? You shrug your shoulders and head off, hoping that this early the queue isn’t too long – though you know it will be.

If you receive medical care regularly, routine visits with the doctor usually involve a set of physical and blood tests that can be bewildering. Knowing what each test measures, and which ones you should be receiving, can help you feel more comfortable and involved in your care.

Tests can monitor the function of organs or systems in the body, such as blood pressure, or can diagnose specific conditions, such as infections. In this article, we’ll look at the monitoring tests most commonly performed at a routine visit to your HIV doctor and what they indicate about your health. We won’t cover HIV-specific tests such as CD4 cell count, viral load, resistance testing and screening for abacavir hypersensitivity. You can find out more about these in our booklet CD4, viral load & other tests.

What should be monitored and why

Everyone should have the health of their major organ systems monitored from time to time, but people with HIV often have additional reasons to do so. Both HIV and its treatment increase the risk of several health issues, including blood problems, cardiovascular disease and liver and kidney damage. We are becoming increasingly aware that bone loss may also be a side-effect of HIV treatment, and a recent study suggests that changes to bone metabolism start as soon as two weeks after starting treatment.¹

The table below outlines the tests commonly done to monitor our health. This is not a comprehensive list, and you may have other tests done, even at a routine visit. Other tests commonly performed include tests for sex hormones like testosterone and estradiol; for other hormones like the thyroid hormones; other tests of liver function like prothrombin clotting time; tests for vitamin and trace mineral deficiency; investigations such as lung function tests and chest X-rays; and any number of different diagnostic tests for specific conditions ranging from cancers to infectious diseases.

The most common tests

 

Blood health	Full blood count
Cardiovascular health	Blood glucose Blood pressure Lipid profile Weight, BMI and waist circumference
Liver health	ALT/AST ALP Bilirubin Albumin
Kidney health	Blood chemistry (urea and electrolytes, creatinine) Estimated glomerular filtration rate (eGFR) Urine dipstick analysis (protein)
Bone health	Blood chemistry (calcium) DEXA Vitamin D

The tests: vital signs and biometrics

Temperature: So routine, we often forget to include it. The normal value quoted is 37ºC, or 98.6ºF.

Blood pressure: A blood pressure reading comprises two measurements: the systolic blood pressure (SBP), read just after the heart has contracted, and the diastolic blood pressure (DBP), read when the heart is relaxed and is refilling.

High blood pressure, also commonly known as hypertension, is a risk factor for cardiovascular disease. For every 20/10 mmHg rise in blood pressure, the risk of cardiovascular disease doubles.²

Weight, BMI and waist circumference: Weight is one measure of health, with lower- or higher-than-normal values, or dramatic changes in weight, indicating potential problems.

Wasting, which includes the unintentional loss of at least 10% of body mass over 30 days, may indicate a potentially fatal condition. Thankfully, HIV-related wasting is much less common now that effective antiretroviral therapy is available, but wasting may indicate other conditions like tuberculosis (TB) and cancer.

Excess body fat is also unhealthy: it is linked to increased risk of death and several diseases. Some are the usual suspects, including high blood pressure, unhealthy blood lipid levels, cardiovascular disease and diabetes, while others might surprise, such as osteoarthritis, sleep apnoea and certain cancers.

Because the human body comes in many shapes and sizes, weight alone is not an adequate way to determine what is dangerous for someone. Body mass index (BMI) and waist circumference attempt to identify unhealthy mass. BMI includes height in its calculation, partially accounting for differences in body shapes.

Waist circumference(measured around the largest part of the belly) is an easy-to-measure indicator of abdominal fat and is independently associated with increased risk of death.

Blood tests

Full blood count (FBC): counts the different types of cells in your blood. There are red blood cells, which carry oxygen; white blood cells, which form part of the immune system and defend us from infection; and platelets, which help the blood to clot. Blood counts are used to diagnose and monitor several diseases and conditions, including anaemia, infections, inflammatory diseases and cancers.

The red blood cell count includes the number of red blood cells, the total amount of the oxygen-carrying molecule haemoglobin and the amount of space red blood cells fill in blood, called haematocrit.

Women generally have fewer red blood cells than men. Anaemia, a deficiency of red blood cells, indicates a clinically significant drop in the ability of blood to carry oxygen. Anaemia is not a disease, but rather a symptom, which may indicate a condition that needs to be investigated.

The white blood cell differential count measures five subtypes of white blood cell. These are:

• Neutrophils, which mobilise a quick response to infection
• Lymphocytes, which co-ordinate a more sophisticated set of responses and ‘remember’ infections
• Monocytes, which target and destroy invading pathogens and foreign matter
• Eosinophils and basophils, which target parasites and mount allergic reactions.

The familiar CD4 cell count measures a subset of the lymphocyte family of cells. A decrease in white blood cell counts indicates an immune dysfunction – the kind seen in AIDS is only one of several types – while an increase may be caused by an infection or tumour. Increases in the different subtypes of white blood cells can be a clue to the underlying problem.

Platelets are cell fragments involved in blood clotting. Having too few platelets increases the risk of uncontrolled bleeding, while having too many increases the risk of excessive clotting, which can cause the blockages that lead to a cardiovascular crisis such as a stroke or pulmonary embolism (a blood clot in the lung).

Blood chemistry: measures the electrolytes (salts) chloride, potassium and sodium, bicarbonate (dissolved carbon dioxide), glucose, creatinine and urea. It often also measures calcium and the protein albumin. These tests monitor kidney function, blood acidity, and levels of electrolytes and sugar. Abnormal levels are generally a sign of other underlying conditions and warrant investigation.

The protein albumin is the most abundant protein in blood, and acts like a sponge to soak up excess fluid. Decreases in albumin are associated with liver damage and a form of kidney disease. They also occur when the body goes into shock or is experiencing severe inflammation. Results from other tests distinguish between the potential causes.

Creatinine is a waste product of muscle metabolism. Because the kidneys are responsible for almost all removal of the compound from the body, blood creatinine levels are a good indicator of kidney function. Creatinine levels can be used to calculate the ‘estimated glomerular filtration rate’ (eGFR), which takes account of the age, sex and ethnic origin of the person. A high blood creatinine level and a low eGFR indicate kidney damage and decreased kidney function.

Levels of specific electrolytes may be abnormal in specific disorders. Diabetes, kidney damage, some forms of heart disease and muscle and nerve problems can all result in electrolyte imbalances. Prescription drugs may also change levels. Other signs and further testing can determine the condition that is causing imbalance.

Levels of blood sugars (also called blood glucose) are used to monitor for signs of diabetes or its precursor, insulin resistance. Diabetes, if left untreated, can lead to serious issues such as cardiovascular disease, kidney damage, increased risk of problems with feet and legs, and damage to the eyes.

Blood for a glucose level test is often drawn after you have fasted; that is, not eaten for at least eight or nine hours. This avoids the fluctuations in glucose levels that occur after eating and provides the most accurate measurement. If results suggest a problem, your doctor is likely to order a more specific test, called an oral glucose tolerance test, that evaluates the body’s ability to control blood glucose levels.

Lipid profile: Blood tests for fats (also called lipids) measure levels of cholesterol and triglycerides. The two forms of cholesterol of interest are low-density lipoprotein (LDL or ‘bad’ cholesterol) and high-density lipoprotein (HDL, or ‘good’ cholesterol). Tests will also measure total cholesterol, as well as another type of fats called triglycerides. Generally, levels of total cholesterol and triglycerides should be as low as possible and so should your LDL:HDL ratio. Unhealthy levels of blood lipids are a risk factor for cardiovascular disease.

Liver function tests: ALT (alanine aminotransferase) and AST (aspartate aminotransferase) are two enzymes found within cells of the liver. Their presence in the blood indicates damage to the liver cells. Results are likely to vary from test to test and so dramatic changes, often presented as multiples of your ‘normal’ reading, are a more reliable indicator of ongoing damage. A change that is up to five times a normal reading is considered mild impairment.

If levels of either enzyme, or their ratio (ALT:AST), change, your doctor is likely to look for indications of potential causes. These could include viral hepatitis infections, starting to take certain antiretroviral or other prescription drugs, drinking a lot of alcohol, being obese, having insulin resistance or diabetes, or having high blood lipid levels.

Alkaline phosphatase and total bilirubin are two other liver tests that may be ordered. Elevated levels of either may be a sign of liver damage or another condition and so results are interpreted along with other liver function test results. One HIV drug, atazanavir (Reyataz), causes a type of rise in bilirubin levels which is usually harmless.

Vitamin D: is not routinely measured but 25-hydroxyvitamin D, the form measured in a blood test, may be, as part of monitoring bone health. Extremely low levels of the vitamin may be associated with bones that do not mineralise (or harden) while more-than-mild deficiency may be linked to osteoporosis (low levels of calcium in the bone, which leads to weakness and fractures). Deficiency has recently been found in a large proportion of people with HIV from diverse geographical regions.³ There is no evidence as yet that supplementing mildly depleted levels of vitamin D is of benefit, but as it’s a cheap supplement, doctors may prescribe it.

Calcium: levels may also be related to bone health, but are only useful diagnostically in cases of severe bone disease. Low calcium may indicate kidney failure or a number of other conditions.

Other tests

Urine dipstick analysis: Testing the chemical composition of urine can detect metabolic and kidney disorders and infections of the urinary tract. Analysis is usually performed using test strips that contain small test pads for each compound of interest. The strips are dipped in the urine sample and colour changes in the pads indicate the results. The most common chemical tests include pH (blood acidity), protein, glucose, ketones, blood, nitrite and bilirubin.

The presence of a compound not normally found in urine is a sign of an underlying disorder. Albumin in the urine can be an early sign of kidney damage, while blood in the urine may suggest internal injury, kidney stones or cancer. Bilirubin in urine can be a sign of liver damage. Glucose and ketones (produced by the liver as part of fatty acid metabolism) are signs of diabetes. The presence of nitrite is a sign of bacterial infection.

DEXA: Dual-energy X-ray absorptiometry (DEXA) is a non-invasive procedure for measuring bone mineral density. Low bone mineral density (called osteoporosis in severe cases) is associated with an increased risk of bone fracture.

DEXA scans are not performed routinely as they are expensive, but will be if osteoporosis is suspected. Scans can be performed of the hip or the spine and results are reported as T-scores or, less commonly, Z-scores. A T-score compares your test result to the bone density of a ‘young, normal’ person of the same sex and is used to diagnose osteoporosis. A Z-score compares your test result to the result of a typical person of your age and sex.

Both scores measure the difference between the reference result and your result using a statistical concept called standard deviations. For example, a T-score of -1.7 indicates that your score was 1.7 standard deviations below the reference score. This means that 92.4% of the population has a score higher than yours. A T-score below -2.5 (lower than 99.4% of the population) is diagnostic for osteoporosis, while a T-score between -1 (lower than 68% of the population) and -2.5 is considered low bone mass, or osteopenia.

Risk assessment tools

In addition, there are two risk assessment tools used to monitor the health of specific organ systems.

Cardiovascular health: The Framingham risk assessment tool is widely used to calculate the risk of a heart attack or death due to heart failure over the next ten years. The tool incorporates many of the traditional risk factors for cardiovascular disease: age, sex, smoking, high blood lipid levels and high blood pressure. The Framingham tool was developed in HIV-negative people, but a similar tool specifically for HIV-positive people is in development.

Bone health: The FRAX questionnaire assesses the risk of fracture and whether a DEXA scan is appropriate. The tool applies to people older than 40; it may underestimate the risk of fracture in people with HIV.

Tests and their 'normal' ranges

 

A ‘normal’ range is not set in stone, and may change as new research comes along. You may find some sources quote rates slightly different from the ones in the table. Do not worry if you are a couple of decimal points outside the limits.

The body keeps some substances, such as glucose, within narrow limits so results significantly outside these are indicative of trouble. In other cases, such as liver enzymes, only results considerably in excess of the normal range matter.

Test results are, confusingly, expressed in two different systems of units: SI (système internationale) units, which are modern metric-system units, and which are generally the ones used in UK health care, and US units (often called ‘conventional’ units in the US), which still appear in many scientific papers.

Table of tests and their normal ranges

Test		Normal or optimal values
		SI units	Conventional (US) units
Body temperature		37ºC	98.6ºF
Blood pressure	Systolic Diastolic	120 to 129 mmHg 80 to 84 mmHg†
Body mass index (BMI)		18.5 to 24.9 kg/m2††
Waist circumference	Men Women	< 94 cm (UK)††† < 80 cm (UK)†††	< 40 in (US)††† < 35 in (US)†††
Complete blood count4
Red blood cells*	Men Women	4.3 to 5.9 trillion/l‡ 3.5 to 5.5 trillion/l‡	4.3 to 5.9 million/mm3‡ 3.5 to 5.5 million/mm3‡
Haemoglobin*	Men Women	2.09 to 2.71 mmol/l 1.86 to 2.48 mmol/l	13.5 to 17.5 g/dl 12.0 to 16.0 g/dl
Haematocrit*	Men Women	0.41 to 0.53 0.36 to 0.46	41 to 53% 36 to 46%
White blood cells		4.5 to 11.0 billion/l‡	4500 to 11,000/mm3
WBC subtypes	Neutrophils Lymphocytes Monocytes Eosinophils Basophils	55 to 70% 20 to 40% 2 to 4% 1 to 4% 0.5 to 1%
Platelets		150 to 400 billion/l‡	150,000 to 400,000/mm3
Lipids
Total cholesterol		< 5.2 mmol/l	< 200 mg/dl
LDL cholesterol		< 2.6 mmol/l	< 100 mg/dl
HDL cholesterol		> 1.0 mmol/l	> 40 mg/dl
Triglycerides		< 1.7 mmol/l	< 150 mg/dl
Blood chemistry**
Bicarbonate (CO2)		22 to 29 mmol/l	22 to 29 mEq/l
Calcium		2.15 to 2.55 mmol/l	8.6 to 10.2 mg/dl
Chloride		95 to 108 mmol/l	95 to 108 mEq/l
Potassium		3.5 to 5.3 mmol/l	3.5 to 5.3 mEq/l
Sodium		133 to 146 mmol/l	133 to 146 mEq/l
Albumin		35 to 50 g/l	3.5 to 5.0 g/dl
Creatinine		70 to 123 mmol/l	0.8 to 1.4 mg/dl
Glucose (fasting)		3.6 to 6.0 mmol/l	65 to 108 mg/dl
Urea		2.5 to 7.8 mmol/l	7 to 22 mg/dl
eGFR		60 ml/min
Liver function tests**
ALT		1 to 21 U/l (international units)
AST		7 to 27 U/l
ALP		50 to 160 U/l
Bilirubin (total)		< 17.1 mmol/l	< 1.0 mg/dl
25-OH vitamin D***		62 to 200 nmol/l	25 to 80 ng/ml
DEXA		-1 to +1 SD

Notes:

† Usually expressed as both units, e.g. “120 over 80”

†† A BMI over 30 kg/m² indicates obesity

††† These are not direct conversions: UK and US guidance differ on the threshold to health risk. In inches, the UK limits normally quoted are 37” in men and 31.5” in women.

§ One trillion is usually expressed as 10¹², a billion as 10^9,  and a million as 10⁶.

* normal ranges vary with altitude

** reference values vary from lab to lab; these values provided only as a general guide

***normal range varies with ethnic background, age, geographic location and sampling season

Want more information?

You can find out about the most common (and some less common) tests and examinations you will have as part of your routine HIV care in NAM’s booklet, CD4, viral load & other tests. More information resources, plus any relevant news reports, are available on our Health monitoring topics pages.

www.labtestsonline.org.uk provides more information on a wide range of medical monitoring tests.