Documents
Resources
Learning Center
Upload
Plans & pricing Sign in
Sign Out

Tests and monitoring in HIV infection

VIEWS: 2 PAGES: 75

									Tests and monitoring in HIV infection

UK standard of care and some other useful tests
Matthew Williams UK CAB

Tests and monitoring in HIV infection

UK standard of care and some other useful tests

Tests and monitoring in HIV infection

CD4 count Viral load Resistance Therapeutic drug monitoring

Tests and monitoring in HIV infection
CD4 count Blood test ●Used to judge how far HIV disease has advanced ●Helps predict the risk of opportunistic infections ●Most useful when it is compared with the count obtained from an earlier test.
●

Tests and monitoring in HIV infection
CD4 count CD4 dips on HIV infection from a normal count of 500-1,500 cells in a cubic millimeter (mm3) of blood (a drop, more or less), recovers somewhat, then falls over time down to as low as 0.

Tests and monitoring in HIV infection
CD4 count

CD4 <200 = greater risk of opportunistic infections (OIs) = “AIDS” = threshold for prophylaxis eg for PCP = bottom of UK threshold for starting combination therapy
CD4 <50 = very great risk of OIs

Tests and monitoring in HIV infection
CD4 count CD4 over 350: treatment not recommended CD4 any count: treatment recommended if “symptomatic”
BHIVA, Treatment of HIV-infected adults with antiretroviral therapy (2006)

Tests and monitoring in HIV infection

CD4 count

CD4 count lower in pregnancy – temporary drop of 50 cells/mm3

Tests and monitoring in HIV infection
CD4 count CD4% - CD4 cells as proportion of all lymphocytes (white blood cells), normally about 40% in adults CD4% is used to monitor babies and children who have higher CD4 counts

Tests and monitoring in HIV infection
Viral load
Blood test (can be other serum eg CSF) ●Used to judge whether treatment is working (early infection?) ●Helps predict the risk of disease progression? ●Most useful when it is compared with the count obtained from an earlier test.
●

Tests and monitoring in HIV infection
Viral load

After infection, viral load surges to a very high for the first weeks or months Often 1,000,000+ copies in a millilitre (mL) of blood, when you are very infectious
Viral load falls as the body controls HIV infection then rises over time as immunity is damaged

Tests and monitoring in HIV infection
Viral load

When you are on HIV treatment, your viral load should be reduced to “undetectable” = <50 copies/mL = 1.7 log10

Tests and monitoring in HIV infection
Viral load
Blip = 1 viral load test detectable (over 50 copies) – 2 of these may be a trend and indicate “virological failure”

Tests and monitoring in HIV infection
Viral load Viral load is usually a PCR (polymerase chain reaction) quantitative (counting) test for HIV RNA - research tests can measure viral load below 50 copies Other tests: bDNA (branched DNA), NASBA (nucleic acid sequence based amplification)

Tests and monitoring in HIV infection
Resistance test Blood test (can be other serum eg CSF) ●Used to judge whether treatment will work ●Involves interpretation ●Two types: genotype and phenotype ●Viral load needs to be over 500 copies/mL for the test to work
●

Tests and monitoring in HIV infection
Resistance test
Resistance test

Tests and monitoring in HIV infection
Resistance test Genotype looks at genetic make up of HIV viruses in infection and compares this to what is known about which mutations lead to resistance
Phenotype looks at whether the drugs work in a test tube

Tests and monitoring in HIV infection
Resistance test
Minority species of resistant virus may be missed by conventional resistance testing (ie if less than 10% of your virus is resistant the test may not pick this up).

In patients without evidence of transmitted resistance, a suboptimal virological response to first-line therapy (<1 log10 copies/mL drop in viral load by 4–8 weeks) should prompt resistance testing at that time.
BHIVA, Treatment of HIV-infected adults with antiretroviral therapy (2006)

Tests and monitoring in HIV infection

Resistance test

Tests and monitoring in HIV infection
Therapeutic drug monitoring (TDM) Measures drug levels in the blood - requires blood samples at recorded time intervals after a drug dose Practical uses for NNRTIs and PIs

Tests and monitoring in HIV infection
Therapeutic drug monitoring (TDM)

Freely available at low (£45/drug) or no cost (if covered by drug company) from University of Liverpool Department of Pharmacology.
http://www.hiv-druginteractions.org/

http://www.delphicdiagnostics.com/

Tests and monitoring in HIV infection
Therapeutic drug monitoring (TDM)
Drug levels vary – much evidence of this – recommended dose is based on averages

University of Liverpool TDM audit – 20-25% of children on NNRTIs or PIs using drugs below therapeutic level.
http://www.i-base.info/htb/v7/htb7-6/University.html

Tests and monitoring in HIV infection
UK standard of care (BHIVA) i) ii) iii)
iv)

All patients should have: a resistance test at diagnosis, before starting HAART, if viral load does not drop by <1log10 after 48 weeks after starting HAART, (genotype) after virological failure

Tests and monitoring in HIV infection

UK standard of care

BHIVA – viral load before and 4-8 weeks after starting treatment (as necessary thereafter)

Tests and monitoring in HIV infection

UK standard of care BHIVA – CD4 count before treatment (as necessary thereafter)

Tests and monitoring in HIV infection
UK standard of care

BHIVA – TDM for management of drug interactions, pregnancy and paediatrics, highly treatment-experienced patients when TDM and resistance test results can be integrated, kidney or liver impairment, transplant patients, drug toxicity, alternative dosing where safety and efficacy has not been established

Tests and monitoring in HIV infection

UK standard of care and some other useful tests

Tests and monitoring in HIV infection
● ● ● ● ●

● ● ●
● ●

Liver enzymes Kidney function Urine Albumin Bone density Glucose Platelets Red blood count White blood count Lipids

Tests and monitoring in HIV infection
● ● ● ● ●

● ● ●

●

C-reactive protein DEXA scan Chest x-ray Sputum serology Lactic acid and blood pH Haemoglobin and iron Serum urea Creatine phosphokinase and lactate dehydrogenase Electrolytes

Tests and monitoring in HIV infection

Tests = blood, blood and more blood...
Many tests require a blood sample

Tests and monitoring in HIV infection
Blood glucose Blood cholesterols and triglycerides Kidney function C-reactive protein Liver enzymes Anaemia Lactic acidosis

Tests and monitoring in HIV infection
Blood glucose Normal range 4-8 millimoles per litre (µmol/L) High glucose ?= kidney disease, neuropathy, insulin resistance, cardiovascular disease Drugs: PIs, tenofovir, AZT?

Tests and monitoring in HIV infection
Blood cholesterols and triglycerides Low-density lipoproteins (LDLs) or "bad" cholesterol, and high-density lipoproteins (HDLs) or "good" cholesterol – ratio is key measure
Insulin resistance, metabolic syndrome, cardiovascular disease

Drugs: PIs, AZT, efavirenz

Tests and monitoring in HIV infection
Blood cholesterols and triglycerides Total cholesterol Target level under 5.2 µmol/L (4-6.4 µmol/L)

Tests and monitoring in HIV infection
Blood cholesterols and triglycerides LDL cholesterol Target level under 3.4 µmol/L

Tests and monitoring in HIV infection
Blood cholesterols and triglycerides HDL cholesterol Target level over 0.9 µmol/L

Tests and monitoring in HIV infection
Blood cholesterols and triglycerides
Cholesterol – CV risk cannot be judged on cholesterol levels alone, HDL:LDL ratio, lifestyle, BMI, age and other factors are important

Smoking!

Tests and monitoring in HIV infection
Blood cholesterols and triglycerides Triglycerides
Fasted levels <2.2 µmol/L normal, 2.2–4.4 µmol/l borderline, >11 µmol/L very high

Each +1.1 µmol/L increased the risk of a heart attack by about 25% in men and 60% in women

Tests and monitoring in HIV infection
Urine Dipstick test Protein – kidney (tenofovir) << mostly albumin ●Glucose – insulin resistance (PIs), kidney (tenofovir, indinavir?, atazanavir?) ●Bilirubin – liver ( X atazanavir)
●

Sensitive but not specific

Tests and monitoring in HIV infection

Kidney function Urine dipstick test or blood test = first test and is indicative but inconclusive

Tests and monitoring in HIV infection
Kidney function

Serum creatinine (blood, not very specific or sensitive) ●Creatinine clearance (blood and/or urine samples over 24 hours) ●Calculated creatinine clearance (1 blood sample) – also called estimated glomular filtration rate (eGFR)
●

Creatinine clearance can increase in pregnancy

Tests and monitoring in HIV infection

Kidney function Different formulas to calculate GFR
http://en.wikipedia.org/wiki/Glomerular_filtration_rate

Tests and monitoring in HIV infection
C-reactive protein Risk of diabetes, hypertension and CV disease Low risk: <1mg/L High risk: >3mg/L
Drugs: PIs?, AZT?

C-reactive protein is a plasma protein produced by the liver (so, another blood test...)

Tests and monitoring in HIV infection
C-reactive protein
C-reactive protein is also marker of inflammation from infection but seems to be a reliable marker for CV disease in HIV regardless of HAART
http://gateway.nlm.nih.gov/MeetingAbstracts/102261383.html

Tests and monitoring in HIV infection
Liver enzymes

AST, ALT, ALP, GGT and bilirubin Many conditions, some specific indications, complicated by hepatitis B and C coinfection, pharmacological agents (all kinds) and food
Drugs: ritonavir, nevirapine, efavirenz, tipranavir, atazanavir, indinavir, d4T - most ARVS and many other drugs may affect the liver

Tests and monitoring in HIV infection
Liver enzymes

ALT (alanine aminotransferase) Normal range 7-30 units/L W, 10-55 units/L M May be more reliable sign of liver damage

Tests and monitoring in HIV infection
Liver enzymes

AST (aspartate aminotransferase) Normal range 9-25 units/L W, 10-40 units/L M Unreliable sign of liver damage
Pregnancy may decrease AST

Tests and monitoring in HIV infection
Liver enzymes ALP (alkaline phosphatase)
Normal range 30-100 units/L W, 45-115 units/L M

Non-specific sign of liver damage Atazanavir and indinavir can raise ALP

Tests and monitoring in HIV infection
Liver enzymes

GGT (gamma glutamyl transferase) Normal range >50 units/L W, >65 units/L M Can be specific sign of liver damage

Tests and monitoring in HIV infection
Liver enzymes

Interpretation requires experience and the whole picture ALP+ GGT normal = bone disease? ●ALP+ GGT+ = bile ducts? liver damage? ●10 x ALT/AST = viral hepatitis? ARVs?
●

Tests and monitoring in HIV infection
Liver enzymes

Bilirubin Direct (unconjugated) 0-7 µmol/L Total 0-17 µmol/L Bilirubin levels slightly higher in males than females, black Africans.
Drugs: atazanavir, indinavir

Tests and monitoring in HIV infection
Liver enzymes Bilirubin Jaundice clinically detectable at levels above 40 µmol/l.
Exception: with atazanavir (or ritonavir) if bilirubin levels around 60-70 µmol/l

Tests and monitoring in HIV infection
Liver enzymes Bilirubin ++ jaundice
Other enzymes ++ may show no outward sign

Tests and monitoring in HIV infection
Liver enzymes

Q: what is the most liver-damaging over-thecounter (OTC) medicine?

Tests and monitoring in HIV infection
Liver enzymes

Q: what is the most liver-damaging over-thecounter (OTC) medicine? A: Paracetamol

Tests and monitoring in HIV infection
Liver enzymes

WHO's top 10 liver-damaging medicines Paracetamol, troglitazone, valproic acid, d4T, halothene, 3TC, ddI, amiodarone, nevirapine, cotrimoxazole
The ABCs of liver disease, Edwin J Bernard, NAM http://www.aidsmap.com/files/file1000630.pdf

Tests and monitoring in HIV infection Liver
PT time – Prothrombin Time

Also called INR - International Normalized Ratio Evaluate the ability of blood to clot properly Not an enzyme test

Tests and monitoring in HIV infection
Liver PT time – Prothrombin Time Monitor anti-coagulants?, bleeding disorders, before surgery Normal range 11-13.5 seconds 1.5-2 times normal = too slow but no consensus on calibration of test as marker of over-fast clotting

Tests and monitoring in HIV infection
Liver PT time – Prothrombin Time
INR = (Pt test / PT normal) ISI
ISI = International Sensitivity Index for tissue factor (1-1.4)

Tests and monitoring in HIV infection
Anaemia

Iron, B12, B6, folic acid, red blood count, heamoglobin (HGB), mean corpuscular haemoglobin (MCH), heamocrit (HCT), mean corpuscular volume (MCV)
Drugs: AZT (pregnant?)

Tests and monitoring in HIV infection
Anaemia Haemocrit
Normal ranges 40-52% M 35-35% W

Low haematocrit = anaemia?

Tests and monitoring in HIV infection
Anaemia Haemoglobin Normal ranges 11.5- to 16.5g W 13-18g M per 100mL blood Low haemoglobin = anaemia?

Tests and monitoring in HIV infection
Anaemia

Mean corpuscular volume Larger = anaemic, B6, B12, folic acid deficiency? Smaller = anaemic, iron deficiency?
AZT (and smoking) can increase MCV without causing anaemia

Tests and monitoring in HIV infection
Anaemia Red blood count (total erythrocytes)
Normal range 3.8-5 W 4.5-6.5 M billion per litre or million per cubic millimitre of blood (1012/L).

Low count = anaemia? but not sensitive or specific = probably a first test

Tests and monitoring in HIV infection
The rest...
Blood chemistry http://www.aidsmeds.com/articles/CSTest_4730.shtml http://www.aidsmeds.com/articles/CBCTest_4729.shtml
A-Z tests http://www.aidsmap.com/cms1031936.asp http://www.labtestsonline.org.uk/

Hepatitis C coinfection – liver and diagnosis http://www.i-base.info/guides/hepc/livertests.html http://www.i-base.info/guides/hepc/hcvtesting.html

Tests and monitoring in HIV infection
Tests to avoid during pregnancy

Amniocentesis ● Chorionic villus sampling ● Fetal scalp sampling ● Cordocentis ● Percutaneous umbilical cord sampling ● Internal fetal labour monitoring (external ultrasound and fetal monitoring OK)
●

Tests and monitoring in HIV infection

Plebotomy (having blood taken)

A cruel and unusual punishment - or nice chat with the nurse?

Tests and monitoring in HIV infection
Blood count reference ranges Red blood count (RBC) 3.8 to 5 W 4.5-6.5 M million per mm3 3 ●White blood count (WBC) 4-11 per mm ●Haemoglobin (HGB, Hg) 11.5-16.5 W 13-18 M g per 100mL 3 ●Neutropils 2-7.5 per mm 3 ●Lymphocytes 1.3-4 per mm 3 ●Platelets 150-440 per per mm ●Mean corpuscular volume (MCV) 80-97
●

Tests and monitoring in HIV infection
Blood count reference ranges CD4 CD4% CD8 400-1,600 per mm3 32-68% 140-1000 per mm3

CD4:CD8 ratio 0.9-6

Tests and monitoring in HIV infection
Sampling

Biggest causes of odd results are „sampling error‟, „processing error‟ or „sample contamination‟ wrong tube, wrong person's sample, crosscontamination, sample too hot/cold/old, wrong reagent, wrongly set up equipment, not reading instructions, misreading output...

Tests and monitoring in HIV infection
Results One result is rarely conclusive
ANY unusual or unexpected results should ALWAYS be retested before making a treatment decision

“Normal” is a difficult word – tests refer to reference ranges, can mean doctor/nurse is happy with results even though high/low

Tests and monitoring in HIV infection
Sensitive v specific Sensitivity = reacts positively
Specificity = reacts positively in right circumstances

Tests and monitoring in HIV infection
Sensitive v specific Sensitivity = rule in
Sensitivity refers to the proportion of people with disease who have a positive test result

Specificity = rule out
Specificity refers to the proportion of people without disease who have a negative test result.

Tests and monitoring in HIV infection
Sensitive v specific
SnNout: when a sign, test or symptom has a high Sensitivity, a Negative result rules out the diagnosis.
SpPin: when a sign, test or symptom has a high Specificity, a Positive result rules in the diagnosis.

Tests and monitoring in HIV infection
Sensitive v specific

Many “rapid” tests are highly sensitive but not specific enough to be definitive – prone to sample contamination Urine dipstick tests ●Fingerprick tests
●


								
To top