1. Module 3: Management of Patients on Antiretroviral Therapy Unit 2: Initiation and Monitoring of ART in Adults and Adolescents

2. Objectives Explain the principles of successful antiretroviral therapy (ART) Explain ART combinations that are used and the rationale for use of national standardized ART regimens Explain drug and non-drug related considerations prior to initiating ART

3. Objectives Explain when ART should be initiated and who should be started on ART Describe when to change or stop ART Describe type of monitoring employed in ART management

4. Goals of ART 1. Maximal suppression of HIV replication 2. Restoration and preservation of immune function 3. Improved Quality of Life 4. Reduction of HIV related Morbidity and Mortality

5. 1. Suppression of HIV Replication ARVs must be taken in combination of at least 3 drugs Strict adherence to treatment is of the upmost importance <95% adherence allows the rapid development of viral resistance Poor adherers do badly Fail treatment much earlier

7. 2. Immune Reconstitution ART prevents CD4 destruction by HIV CD4 cell count can recover Improved function of CD4 cells CD4 cells are central to the immune system So there is improved overall function of the immune system It takes from 6 to 8 weeks for this to become evident clinically

8. 3. Improvement of QOL Decreased hospitalizations Decreased risk of illnesses Increased general well-being Reversal of weight loss Ability to return to work

9. Take-home Messages about ART Not an emergency treatment Benefits take 6 to 8 weeks Should not be initiated while an inpatient Treat opportunistic infections first OI’s cause >90% of morbidity in HIV >90% of OI’s are simple to treat ART is only one part of HIV Care All who require ART should first be on CPT first Optimize nutrition

10. Take-home Messages about ART Adherence counselling essential Patients should be able to demonstrate an understanding of: Importance of strict adherence Their ability to afford drugs long term Life-long treatment, monthly follow-up The Kenyan National Guidelines should be followed “If you don’t agree with them, campaign for a change rather than ignoring them!”

11. Rationale Behind Standardized ARV Therapy Success of TB treatment program Simplicity of prescribing Preservation of certain ARV’s on a population level Simple sequencing of 1 st to 2 nd line Increased efficiency in drug procurement Cost and availability of FDC’s

12. Standard 1 st Line Regime for Adults and Adolescents Lamivudine + Stavudine + Nevirapine Lamivudine + Stavudine + Efavirenz or

13. Standard 2nd Line Regime for Adults and Adolescents Zidovudine + Didanosine + Lopinavir/Ritonavir Zidovudine + Didanosine + Nelfinavir or

14. For Patients on Non-standard 1 st line Regimes… 1 st Line D4T+ddI+NNRTI AZT+3TC+ABC AZT+3TC+PI 2 nd Line AZT+3TC+LPV/r NNRTI+LPV/r+d4T NNRTI+ABC+ddI

15. A note on Fixed Dose Combinations (FDC’s) WHO Approved FDC’s are available for: d4T/3TC/NVP D4T/3TC AZT/3TC Advantages Decreased pill burden Increased adherence Mono or duo-therapy not possible Lower cost Simplify stock control and forcasting GoK has chosen these for the National roll-out

16. When to Start ART in Adults and Adolescents Where CD4 testing available WHO II & III when CD4 < 200/mm 3 WHO stage IV irrespective of CD4 level

17. When to Start ART in Adults and Adolescents Where CD4 Testing Unavailable WHO II when total lymphocyte count <1200/mm3 WHO III & IV regardless of total Lymphocyte count

18. Guidance on Clinical Criteria CD4 levels are not “hard and fast” rules A sick, deteriorating patient with a CD4 of 210 should not be excluded from ART if otherwise able and keen to begin A very well, stable patient with a CD4 of 180 could reasonably opt for close follow up and deferral of ART to a later date

19. Pregnancy and ART Not a contraindication ART In general, best to defer to after the first trimester (after organogenesis) EFV contraindicated ART greatly decreases vertical transmission Also allows mother to remain well to care for her child

20. Monitoring of ART (1) ART is monitored using: Clinical information Body Weight Signs and symptoms Past and present medical history Physical examination

21. End Points in Clinical Monitoring Look for: Decrease or disappearance of symptoms Increase in body weight Decrease in frequency and severity of OIs

22. Monitoring of ART (2) ART is monitored using: Laboratory Parameters Minimum - HIV Test, Hb, pregnancy test Standard - FBC, SGPT/ALT, Creatinine Desirable - CD4 Optional/Ideal - Viral Load

23. Schedule of Laboratory Monitoring TestBaseline1-2 months 6 months 12 months 18 months 24 months CD4 XX1X1 XX1X1 X FBC XXXXX1X1 X Creatinine XXX Pregnancy XX1X1 X1X1 X1X1 X1X1 X1X1 SGPT/ALT XXXXXX Urinalysis XX1X1 X1X1 XX1X1 X X 1 : If clinically indicated