1. HIV i-Base: Training for Advocates, 10/2004www.i-Base.info Section 3: Introduction to ARV Therapy HIV i-Base STEP EATG HIV Training for Advocates

2. HIV i-Base: Training for Advocates, 10/2004www.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

3. HIV i-Base: Training for Advocates, 10/2004www.i-Base.info HIV lifecycle HIV uses CD4 cells as factories to make hundreds of copies of itself. Different drugs work at different stages of the HIV life cycle.

4. HIV i-Base: Training for Advocates, 10/2004www.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

5. HIV i-Base: Training for Advocates, 10/2004www.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

6. HIV i-Base: Training for Advocates, 10/2004www.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

7. HIV i-Base: Training for Advocates, 10/2004www.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

8. HIV i-Base: Training for Advocates, 10/2004www.i-Base.info C Max Drug concentration 0 dos e 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

9. HIV i-Base: Training for Advocates, 10/2004www.i-Base.info dose C Max 0 dose Each dose taken on time makes sure that you keep above a mimimum level Drug concent ration Time C Min or C tough Drug absorption.2

10. HIV i-Base: Training for Advocates, 10/2004www.i-Base.info dose Increased risk of side effects 0 Increased risk of resistance 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

11. HIV i-Base: Training for Advocates, 10/2004www.i-Base.info 2-3 years 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 Missed dose Late dose Drug levels and resistance.2 Drug concentration

12. HIV i-Base: Training for Advocates, 10/2004www.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

13. HIV i-Base: Training for Advocates, 10/2004www.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