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HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
Section 3: Introduction to ARV Therapy
HIV i-Base • STEP • EATG
HIV Training for Advocates
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
• HIV is continually reproducing - an it uses CD4 cells as factories to produce more virus.
• The drugs work at different parts of the HIV lifecycle
• Available drugs work in one of four ways:
i) reverse transcriptase inhibitors (RTIs, nukes)
ii) NNRTIs - non-nukes
iii) protease inhibitors (PIs)
iv) entry inhibitors (T-20)
Combination therapy
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
HIV lifecycleHIV lifecycleprotease inhibitorsentry inhibitorsnukes &non-nukes(NNRTIs)HIV virusCD4 cellHIV uses CD4 cells as factories to make hundreds of copies of itself. Different drugs work at different stages of the HIV life cycle.
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
1. There are now approx 20 approved anti-HIV drugs and more in development (see page 16 of the i-Base guide)
2. Some are more potent than others
3. A few cannot be used together (ie d4T and AZT)
4. Recent studies and guidelines recommend using two RTIs and either one NNRTI or one PI-based combination as being most effective:
i) AZT / 3TC / efavirenz
ii) AZT / 3TC / lopinavir/r (Kaletra)
5. BUT many other combinations are better for some people: - every drug has different advantages and disadvantages, and newer drugs are being used as first line therapy
Choice of drugs
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
• HIV treatment is different to other medications
• Weak treatment (less than 3 drugs) or missing doses (even one dose a week) will lead to resistance, and the combination will fail
• Once resistance develops it never reverses
• Resistance will make the next combination less likely to succeed - because there is cross-resistance between most drugs in each class
How to get treatment right
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
• When HIV reproduces - it makes mistakes - so new virus is not exactly the same
• Most of these changes do not matter, but some will stop HIV drugs from working
• Resistance only develops when you are taking treatment with a detectable viral load
• Main cause of resistance is poor adherence
Resistance
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
• A ‘little’ HIV treatment is very dangerous
• Treatment needs to be ‘all or nothing’
• Missing doses (even one dose a week) can lead to resistance if you do this regularly
• This is because you need to keep levels of each drug in your combination above a minimum level
• Once you start treatment, getting a strategy to never miss a dose is the most important thing you have to do in your life. Especially critical for first months.
Adherence
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
C Max
Drug concentration
0
dose
Time
After taking a drug, levels peak quickly and then slowly drop as the drug is eliminated - every drug has its own drug absorption curves
T Max
AUC = Area Under Curve
T 1/2
Drug absorption
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
dose
C Max
0
dose dose
Each dose taken on time makes sure that you keep above a mimimum level
Drug concentration
Time
C Min or C tough
Drug absorption.2
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
dose
Increased risk of side effects
0
Increased risk of resistance
dose dose dose
Taking drugs at the exact time makes sure that you keep above a mimimum level
Drug levels and resistance.1
MEC(Minimum Effective Concentration)
Drug concentration
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
Accuracy of your dosing will keep you out of the risk zone for resistance
Increased risk of side effects
MEC(Minimum Effective Concentration)
0
Increased risk of resistance
dose Misseddose
dosedoseLatedose
Drug levels and resistance.2
Drug concentration
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
• Be an active patient
• Nearly always a choice in every situation - combination therapy is not ‘fixed’ but very flexible
• Effective treatment includes Quality of Life
• Research alternatives
• Follow research for new information (ie lipodystophy)
Side Effects
HIV i-Base: Training for Advocates, 10/2004 www.i-Base.info
Focus of huge quantity of research:
- New drugs
- New targets
- New strategies - treatment interruptions
- boosted-PI monotherapy
- boosting immune responses
- individualising treatment (IQ etc)
Future development