An Introduction to Antiretroviral Therapy
Drug Adherence - A Key to Treatment SUCCESS

Integrated Treatment Centre 11 / 2004
Special Preventive Programme
Centre for Health Protection Department of Health

Preface
1. The Human Immunodeficiency Virus (HIV) life cycle
2. What is antiretroviral therapy?
3. Effects of antiretroviral therapy
4. What kinds of antiretroviral therapy are available in Hong Kong?
5. When to consider using antiretroviral therapy?
6. Special attention while taking antiretroviral drugs
7. Nine tips on successful drug taking
8. How to control over antiretroviral therapy?
9. How to know whether treatment is working?
10.What is meant by "undetectable" viral load?
11. The importance of drug adherence
12. Degree of drug adherence
13. Non-adherence can lead to drug resistance
14. Signs of treatment failure
15. Side effects of antiretroviral therapy
16. Managing side effects
17. The use of antiretroviral agents for prophylaxis
18. Conclusion
Appendix I: Classes of antiretroviral drugs
Appendix II: Progress sheet
Appendix III: Useful telephone numbers and websites



PREFACE
The use of antiretroviral therapy can effectively control HIV and its disease progress.
Successful treatment depends on how you know about and get the most from your medicine over a long period of time.
Stay on your medication and work together with your health care providers is a smart way to reach the goal.
This booklet aims to promote your understanding about how antiretroviral therapy can help you live a longer and healthier life.
If you have further questions after reading this booklet, please be sure to talk to your doctor and / or other health care providers to obtain the feedback.

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1. The Human Immunodeficiency Virus (HIV) life cycle
HIV enters a healthy CD4 cell. Once inside the cell, HIV coverts its own genetic material RNA into DNA using the enzyme reverse transcriptase. This new DNA acts as a blueprint directing the infected cell to make new virus particles. Mature viral cores are produced through action of viral protease after budding. The new virus is then released and can infect other healthy cells. Thus, the function of immune system will be progressively destroyed.

The Human Immunodeficiency Virus (HIV) life cycle

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2. What is antiretroviral therapy (ART) ?
The antiretroviral agents attack HIV at different stages of its life cycle to inhibit HIV replication and thus bring the viral load down. Combination therapy of two or more drug components has become the standard of treatment of HIV disease.
Cocktail" is a colloquial term for HIV combination therapy.
Highly active anti-retroviral therapy (HAART)
HAART refers to very potent regimen in which almost invariably inhibits viral replication to an undetectable level in the blood. An example of HAART is the use of triple therapy comprises 2 Nucleoside Reverse Transcriptase Inhibitors (NRTI) and 1 Protease Inhibitors (PI).

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3. Effects of antiretroviral therapy

Restore health and defense function

Decline in AIDS morbidity, hospitalization and mortality

Improve well-being

Improve the quality of life

Prolong survival of the patients with AIDS

Goals of Therapy
Suppression of viral replication to an undetectable level is the goal of HAART. Effectiveness of the treatment is readily demonstrable by a precipitous fall in plasma viral load and often a rise in CD4 count.

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4. What kinds of antiretroviral therapy are available in Hong Kong?
There are three classes of antiretroviral drugs available in Hong Kong (Appendix I):
(I) Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI)
Action: HIV's enzyme called reverse transcriptase convert RNA to DNA. NRTI block reverse transcription by providing faulty building blocks that interrupt the process.
Currently available drugs in this class are:

1. Zidovudine
(AZT)
(Retrovir)
2. Didanosine
(ddI)
(Videx)
3. Didanosine EC
(ddIEC)
(Videx EC)
4. Lamivudine
(3TC)
(Epivir)
5. Zalcitabine
(ddC)
(Hivid)
6. Stavudine
(d4T)
(Zerit)
7. Combivir
(CBV)
8. Abacavir
(ABC)
(Ziagen)
9. Tenofovir
(TDF)
(Viread)
10. Trizivir
(ABC+AZT+3TC)

(II) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Action: NNRTI stop HIV production by binding directly onto reverse transcriptase and prevent the enzyme from converting RNA to DNA.
Currently available drugs in this class are:

1. Efavirenz
(EFZ)
(Sustiva)
2. Nevirapine
(NVP)
(Viramune)

(III) Protease Inhibitors (PI)
Action : PI block the action of an enzyme, called Protease that cuts HIV protein chains into specific proteins needed to assemble a new copy of HIV. Therefore, PI prevent the cell from producing new HIV.
Currently available drugs in this class are:

1. Indinavir (IDV) (Crixivan)
2. Saquinavir (SQV) (Hard gel-Invirase, Soft gel-Fortovase)
3. Ritonavir (RTV) (Norvir)
4. Nelfinavir (NFV) (Viracept)
5. Kaletra (LPV+RTV)  

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5. When to consider using antiretroviral therapy?
The doctor will consider using antiretroviral therapy when the infected individual has suffered clinically or immunologically from the virus or has at a heightened risk of disease progression. The following are the indicators for treatment: *

  • Low CD4 count
  • High viral load level
  • Signs of opportunistic infection
  • Psychologically well prepared to comply with this long-term treatment in order to achieve the goal of therapy

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6. Special attention while taking antiretroviral drugs
Different drugs would have different precautions, e.g.:

  • Some drugs work best when they are taken with food while some should be taken on an empty stomach.
  • May need to increase water intake.
  • Some kinds of food, drugs, Chinese medicines or alcohol should be avoided to prevent adverse reaction.
  • Some drugs need to be stored in a refrigerator or special container.

    Thus, the infected individual should follow the instruction of health care providers when taking antiretroviral drugs.

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7. Nine tips on successful drug taking

Commit to drug taking strongly
Fit the drug regimen into your daily activities
Keep drugs in the places you usually go
Know well your drug regimen in terms of the right dosage, frequency and ways of drug taking
Bring along a bottle of water for drug taking
Make use of an alarm clock, a pager or chart to remind yourself the time of drug taking
Use a pill box to contain one-day medication to remind yourself of the correct dosage
Seek help from health care providers to work out a drug schedule that suit you most
Seek support from significant others

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8. How to control over antiretroviral therapy?

Make a personal commitment to your therapy

Keep in close touch with your health care providers

Attend regular follow-up

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9. How to know whether treatment is working?
Health monitoring blood test:
CD4 count - reflect how strong immune system is
Viral load measurement - measure level of HIV in blood

In general, treatment is considered to be working if the viral load is falling or remains low, and the CD4 level is rising or remains stable.

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10. What is meant by "undetectable" viral load?
Undetectable viral load means that HIV level is too low to be picked up by the viral load test. HIV are still in the body and can transmit to others through sexual and blood contact. Therefore, it is essential to continue treatment and take precautions against its spread e.g. safer sex.

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11. The importance of drug adherence
The most important element in the success of your anti-HIV treatment is to strictly adhere to the drug regimen. Good drug adherence can prevent treatment failure and the emergence of resistance. Poor drug adherence will lead to the development of drug resistance, limiting the effectiveness of therapy.
Thus, the most important thing you can do to stay healthy is always to take your drugs in the right way and at the right time.

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12. Degree of drug adherence
The nurse counsellor usually calculates your degree of drug adherence by:

NO. of doses of ART taken ÷ No. of prescribed doses of ART × 100%

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13. Non-adherence can lead to drug resistance
Drug resistance means the reduction of a drug's ability to work against HIV. Resistance is thought to occur when its target mutates, changing its structure so that the drug can no longer bind to work as well as it used to.
Missing doses or taking even short "drug holidays" give the virus change its form and multiply. When you start taking your drugs again, they may not work as well. Thus, non-adherence to drug regimen can lead to drug resistance.
Cross-resistance:
The mechanism by which HIV that has developed resistance to one drug may also be resistant to other similar drugs.

DRUG RESISTANCE

Taking drugs regularly helps you control the virus

Taking your drugs on time, every time is essential and has its reward:

  • Lower or undetectable viral load result
  • Higher CD4 count, increase/maintain immune function.

Non-adherence enables the virus to gain control again

The best way to avoid resistance is to adhere to the regimen - EVERYDAY, EVERY TIME

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14. Signs of treatment failure

  • Increase viral load
  • Decrease CD4 count
  • Increase risk of disease progression
  • Increase hospitalization and risk of death

Missing doses or taking the wrong doses can lead to drug resistance. You can quickly become resistant to antiretroviral drugs if you do not take them at the right time, in the right way and in the right dose. If drug failure is evident in terms of clinical, immunological, or virological deterioration, change of antiretroviral regimen is indicated.

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15. Side effects of antiretroviral therapy
Many side effects are temporary. If you encounter unpleasant side effects, do not discontinue the drugs or alter the dosage by yourself. You should discuss your problem with the health care providers to understand the alternatives of the way and time of drug taking, so that a more appropriate drug taking plan could be developed.

Transient side effects:

  • Nausea/ vomiting
  • Diarrhoea
  • Allergy
  • Headache
  • Fatigue
  • Fever
  • Central Nervous System (CNS) symptoms (e.g. dizziness, insomnia, drowsiness, nightmares, inability to concentrate, etc.)

Potential long term side effects:

  • Anaemia (low red blood cell count)
  • Kidney stones
  • Deranged liver function
  • Peripheral neuropathy
  • Pancreatitis
  • Redistribution of fat (lipodystrophy)
  • Metabolic problems (e.g. increase blood fats/ blood sugar)
  • Neutropenia (an abnormal decrease in the number of neutrophils in the blood)

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16. Managing side effects
Side effects to antiretroviral drugs are common during the first few weeks of treatment. However, these symptoms will often pass as your body gets used to the drugs. You should report any unusual symptoms to your doctor/health care providers. If necessary, your doctor will prescribe medications to help you get over the initial period. The following is a quick reference for managing side effects of antiretroviral drugs.

Managing side effects: A quick reference chart

Diarrhoea
Self management:
  • Eat white rice, toast, oatmeal, apple sauce, or bananas
  • Avoid spicy foods, fatty foods, and foods that promote gas, e.g. peanuts, onion
  • Avoid high fibre food, such as brown rice or whole grain bread
  • Drink a lot of liquid to replace fluids lost

Consult your doctor:

  • Check for signs of infections
  • Prescribe medications for diarrhoea


Upset Stomach (Nausea, Vomiting, Poor Appetite)
Self management:
  • Eat dry foods like crackers, toast, and dry cereal
  • Sip clear liquids like ginger ale or juice mixed with water
  • Eat foods that appeal to you even when you are not hungry
  • Eat small and frequent meals
  • Avoid eating very sweet , spicy or fatty food
  • Avoid lying down directly after a meal
  • Avoid drinking fluids immediately before, with or after meals

Consult your doctor:

  • Prescribe medications for upset stomach
  • Prescribe medications to improve your appetite
  • Clarify with your doctor about your drug taking pattern and the suitable timing of meals to avoid gastric upset


Feeling Tired (Fatigue)
Self management:
  • Take a balance diet and exercise regularly
  • Get adequate rest
  • Ask for help with work so as to save energy for important tasks

Consult your doctor:

  • Check for signs of anaemia


Dizziness, Confusion, and Sleeping Problems
Self management:
  • Take medications at the best time of day to reduce side effects, e.g. Efavirenz is best taken at bedtime
  • Stay in bed if possible

Consult your doctor:

  • Consider other causes, leading to the side effect e.g. depression
  • Enquire about the change of drugs or time of drug taking
  • Prescribe medications for discomfort


Headache
Self management:
  • Take adequate rest
  • Do relaxation exercise
  • Listen to light music

Consult your doctor:

  • Prescribe medications for headache


Fat Problems (Lipodystrophy)
Self management:
  • Get regular exercise and eat a healthy diet. This may not reduce lipodystrophy, but it will keep your weight and overall body fat at a healthier level

Consult your doctor:

  • Enquire about experimental treatments to be used for repairing facial fat changes


Nerve Problems, Tingling Hands and Feet (Neuropathy)
Self management:
  • Avoid walking or standing for a long period of time
  • Soak your feet in cool water
  • Massage hands and feet
  • Avoid wearing tight socks or shoes

Consult your doctor:

  • Enquire the possibility of change of drugs
  • Refer to see a neurologist
  • Prescribe medications for neuropathy


Liver Problems
Self management:
  • Quit or reduce alcohol drinking

Consult your doctor:

  • Monitor liver enzyme blood tests regularly
  • Enquire about changing of drugs or alternative therapy


Metabolic Problems
Self management:
  • Exercise on a regular basis if possible
  • Quit or reduce smoking

Consult your doctor:

  • Monitor cholesterol, triglycerides, and glucose tests (the blood tests that measure fats and sugar in your blood) regularly


Bone Problems
Self management:
  • Get enough calcium and vitamin D from food, such as fortified soy, rice milk
  • Do weight-bearing exercise like walking or weight lifting

Consult your doctor:

  • Prescribe medications for discomfort

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17. The use of antiretroviral agents for prophylaxis
Effectiveness of antiretroviral drugs is already well-proven as prophylaxis to reduce the risk of HIV transmission in two specific health care settings:

  • Perinatal infection (mother to child transmission)
  • Post occupational exposure prophylaxis

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18. Conclusion
By using antiretroviral therapy and adopting good drug adherence practice, you can stay a healthy life. Be relax, take nutritious food, do regular exercise, join a support group and develop a hobby are some smart ways to maintain good health and improve your quality of life.

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APPENDIX I

Classes of antiretroviral drugs
(A) Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI)
  Drug Dosage Potential side effects Remarks
1. Zidovudine
(AZT)
Retrovir
100mg/cap
200mg
3 times/day
or
300mg
2 times/day
  • Anaemia
  • neutropenia
  • G I intolerance
  • Headache
  • Insomnia
  • Asthenia
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea

  • If nausea, take after a meal
2. Didanosine (ddI)
Videx
25mg/tab
100mg/tab

125mg or 200mg
2 times/day
  • Peripheral neuropathy
  • Pancreatitis
  • Nausea
  • Diarrhea
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea
  • Chewed/crushed/ dissolved
  • Take on empty stomach
  • Take with IDV at least 1 hr apart
3. Didanosine EC (ddIEC)
Videx EC
250mg/tab
400mg/tab
250mg or 400mg daily
  • Peripheral neuropathy
  • Pancreatitis
  • Nausea
  • Diarrhea
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea
  • Take on empty stomach
  • Take with IDV at least 1 hr apart
  • Take with meal if take TDF together
4. Lamivudine
(3TC)
Epivir
150mg/tab
150mg 2 times/day
  • Minimal toxicity
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea
  • Rapid emergence of resistant strains if non-adherent
5. Zalcitabine (ddC)
Hivid
0.75mg/tab
0.75 mg
3 times/day
  • Peripheral neuropathy
  • Stomatitis
  • Pancreatitis
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea
 
6. Stavudine(d4T)
Zerit
30mg/cap
40mg/cap
30mg or 40mg
2 times/day
  • Peripheral neuropathy
  • Lipodystrophy
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea
  • Pancreatitis
  • Rapidly progressive ascending neuromuscular weakness (rare)
 
7. Combivir (CBV)
=150mg 3TC + 300mg AZT/tab
1 tab
2 times/day
  • Anaemia
  • Neutropenia
  • Headache
  • G I intolerance
  • Insomnia
  • Asthenia
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea
 
8. Abacavir (ABC)
Ziagen
300mg/tab
300mg
2 times/day
  • Hypersensitivity reaction (5% of people) symptoms may include fever, rash, nausea, vomiting, malaise, fatigue or loss of appetite, respiratory symptoms such as sore throat, cough, shortness of breath
  • If there is fever , rash, report to health care workers at once
9. Tenofovir (TDF)
Viread
300mg/tab
300mg daily
  • Asthenia
  • Headache
  • G I intolerance
  • Flatulence
  • Lactic acidosis with hepatic steatosis (rare): fatigue, severe vomiting, dyspnoea
  • Rare report of renal insufficiency
  • Take with meal
  • Dosage adjustment in renal insufficiency
10. Trizivir
(ABC + AZT + 3TC)
1 tab
2 times/day
  • Anaemia
  • Neutropenia
  • G I intolerance
  • Headache
  • Insomnia
  • Asthenia
  • Lactic acidosis with hepatic steatosis: fatigue, severe vomiting, dyspnoea
  • Hypersensitivity reaction
  • If there is any flu like symptom fever, rash, report to health care workers at once

B) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)

  Drug Dosage Potential side effects Remarks
1. Efavirenz (EFZ)
Stocrin, Sustiva
200mg/cap
600mg/tab
600mg daily
(preferably at bed time)
  • Rash
  • CNS symptoms: dizziness, somnolence, insomnia, drowsiness, nightmares, hallucinations, poor concentration (usually subside in 2-4 weeks if really appear)
  • Increased transaminase levels
  • Decrease CNS symptoms if take at bed time
  • Pregnancy is contraindicated
2. Nevirapine
(NVP)
Viramune
200mg/tab
200mg daily for 2 weeks,
then 200mg
2 times/day
  • Rash
  • Symptomatic hepatitis
  • Anti-TB drugs and oral contraceptive pills should be used with caution
  • Rapid emergence of resistant strains if non-adherent

(C) Protease Inhibitors (PI)

  Drug Dosage Potential side effects Remarks
1. Indinavir (IDV)
Crixivan
200mg/cap
400mg/cap
800mg Q8h 3 times/day
  • Nephrolithiasis
  • G I intolerance
  • Increased indirect bilirubinemia
  • Misc.: headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, and hemolytic anaemia
  • Fat redistribution
  • Lipid abnormalities
  • Hyperglycemia
  • Take with empty stomach
  • Drink water 1.5 litre/day
  • Avoid grapefruit juice
2. Saquinavir (SQV)
Invirase (hard gel)
200mg/cap
Fortovase (soft gel)
200mg/cap
Invirase 600mg 3 times/day
Fortovase 1200mg 3 times/day
  • Headache
  • G I intolerance
  • Elevated transaminase enzymes
  • Hyperglycemia
  • Fat redistribution
  • Lipid abnormalities
  • Possible increased bleeding episodes in patients with hemophilia
  • Take after meal, preferably fatty to increase absorption
  • Rifampicin & Rifabutin are contraindicated with SQV
  • Fortovase (soft gel) should be refrigerated or stored at room temperature <25°C (up to 3 months)
3. Ritonavir (RTV)
Norvir
100mg/cap
syrup 80mg/ml
600mg 2 times/day
  • Headache
  • G I intolerance
  • Paresthesias – circumoral and extremities
  • Hepatitis
  • Pancreatitis
  • Asthenia
  • Taste perversion
  • Lab.: Triglycerides increase >200%, transaminase elevation, elevated CPK and uric acid
  • Hyperglycemia
  • Fat redistribution
  • Lipid abnormalities
  • Possible increased bleeding episodes in patients with hemophilia
  • Capsules should be refrigerated. If stored at room temperature <25°C, it is stable for 30 days
  • Take after meal to improve tolerance
  • Need dosage adjustment if take with SQV
  • Avoid self-prescribe drugs because of drug interaction
4. Nelfinavir
(NFV)
Viracept
250mg/tab
750mg 3 times/day
or
1250mg 2 times/day
  • Diarrhoea
  • Hyperglycemia
  • Fat redistribution
  • Lipid abnormalities
  • Serum transaminase elevation
  • Possible increased bleeding episodes in patients with hemophilia
  • Take with meal
5. Kaletra
= Lopinavir (LPV) 133.3mg + Ritonavir (RTV) 33.3mg/cap
3 capsules 2 times/day
  • Diarrhoea
  • G I intolerance
  • Asthenia
  • Elevated serum transaminases
  • Hyperglycemia
  • Fat redistribution
  • Lipid abnormalities
  • Possible increased bleeding episodes in patients with hemophilia
  • Take with meal
  • Use additional type of contraception since Kaletra may reduce the effectiveness of oral contraceptives
  • Should be refrigerated. If stored at room temperature <25°C, it is stable for 2 months

Reference:
Department of Health, Guidelines for the Use of Antiretroviral Agents in HIV-I-Infected Adults and Adolescents. convened by DHHS. March, 2004. P.59-64

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APPENDIX II

Progress Sheet

Date
CD4 Count
Viral Load
Remarks
       
       
       
       
       
       
       
       
       
       
       
       
       
       
       
       
       
       

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APPENDIX III

Useful telephone numbers and websites:

Government Organizations:

‧ Kowloon Bay Integrated Treatment Centre
Tel: 2117 0333

‧ Red Ribbon Centre
Tel: 2304 6268
http://www.rrc.gov.hk

‧ AIDS Hotline
Tel: 2780 2211
http://www.27802211.com

‧ Harm Reduction Hotline
Tel: 2112 9977

AIDS Non-governmental Organizations & Drug related Organizations:

‧ Hong Kong AIDS Foundation
Tel: 2560 8528
Hotline: 2513 0513
http://www.aids.org.hk

‧ AIDS Concern Hotline
Tel: 2898 4422
http://www.aidsconcern.org.hk

‧ The Society for AIDS Care
Tel 2559 2006
http://www.aidscare.com.hk/cindex.html

‧ Teen AIDS
Tel: 2554 3399
http://www.teenaids.org.hk

‧ The Society for the AIDS and Rehabilitation of Drug Abusers (SARDA) Hotline
Tel: 2574 3300

Overseas Internet / Website for more information about HIV Treatment:

http://www.aidsmap.com
http://www.hivresources.com
http://www.iasusa.org
http://www.medscape.com
http://www.unaids.org

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