Download Drug concentration

HIV i-Base • STEP • EATG
HIV Training for Advocates
Section 3: Introduction to ARV Therapy
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info
Combination therapy
•
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)
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info
HIV lifecycle
H IV virus
entry inhi bitors
C D4 cell
nukes &
non-nukes
(N NRTIs)
HIV i-Base: Training for Advocates, 10/2004
protease i nhibi tor s
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HIV uses CD4 cells as factories to make hundreds of copies of itself. Different drugs work at different stages of the HIV lif
Choice of drugs
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
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info
How to get treatment right
•
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
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info
Resistance
• 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
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info
Adherence
•
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.
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info
Drug absorption
After taking a drug, levels peak quickly and then slowly drop as the
drug is eliminated - every drug has its own drug absorption curves
C Max
Drug
concentration
AUC = Area Under Curve
0
T Max
dos
e
HIV i-Base: Training for Advocates, 10/2004
Time
T 1/2
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Drug absorption.2
Each dose taken on time makes sure that you keep above a mimimum level
C Max
Drug
concent
ration
C Min or C tough
0
Time
dose
dose
HIV i-Base: Training for Advocates, 10/2004
dose
www.i-Base.info
Drug levels and resistance.1
Taking drugs at the exact time makes sure that you keep above a mimimum level
Increased risk of side effects
Drug
concentration
MEC
(Minimum
Effective
Concentration)
Increased risk of resistance
0
dose
HIV i-Base: Training for Advocates, 10/2004
dose
dose
dose
www.i-Base.info
Drug levels and resistance.2
Accuracy of your dosing will keep you out of the risk zone for resistance
Increased risk of side effects
Drug
concentration
MEC
(Minimum
Effective
Concentration)
Increased risk of resistance
0
dose
dose
HIV i-Base: Training for Advocates, 10/2004
Missed
dose
Late
dose
dose
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Side Effects
•
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)
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info
Future development
Focus of huge quantity of research:
- New drugs
- New targets
- New strategies - treatment interruptions
- boosted-PI monotherapy
- boosting immune responses
- individualising treatment (IQ etc)
HIV i-Base: Training for Advocates, 10/2004
www.i-Base.info