3. Is HIV and AIDS the same thing?

4. HIV “Human Immunodeficiency Syndrome” A specific type of virus (a retrovirus) HIV invades the helper T cells to replicate itself.

5. AIDS Acquired Immunodeficiency Syndrome HIV is the virus that causes AIDS Disease limits the body’s ability to fight infection A person with AIDS has a very weak immune system

6. Four Stages of HIV

7. Stage 1 - Primary Short, flu-like illness - occurs one to six weeks after infection no symptoms at all Infected person can infect other people

8. Stage 2 - Asymptomatic Lasts for an average of ten years This stage is free from symptoms There may be swollen glands The level of HIV in the blood drops to very low levels HIV antibodies are detectable in the blood

9. Stage 3 - Symptomatic The symptoms are mild The immune system deteriorates emergence of opportunistic infections and cancers

10. Stage 4 - HIV  AIDS The immune system weakens The illnesses become more severe leading to an AIDS diagnosis

11. Opportunistic Infections associated with AIDS Bacterial Tuberculosis (TB) Strep pneumonia Viral Kaposi Sarcoma Herpes Influenza (flu)

12. Opportunistic Infections associated with AIDS Parasitic Pneumocystis carinii Fungal Candida Cryptococcus

13. Modes of HIV/AIDS Transmission

14. Through Bodily Fluids Blood products Semen Vaginal fluids Breast Milk

15. Through IV Drug Use Sharing Needles Without sterilization Increases the chances of contracting HIV

16. Through Sex

17. Mother-to-Baby Before Birth During Birth Postpartum After the birth

18. Treatment Options

19. Antiretroviral Drugs Nucleoside Reverse Transcriptase inhibitors Zidovudine, Didanosine, Emtricitabine Non-Nucleoside Transcriptase inhibitors Nevirapine, Etravirine Protease inhibitors Ritonavir, Atazanvir Entry /fusion inibitors:Maraviroc,Enfuveride vertide

20. 1 st effective therapy for HIV was the nucleoside reverse transcriptase inhibitor zidovudine but this drugs or even in combination of drugs from same group were unable to suppress virus for long periods of time and patient eventually dies Later on the development of other drugs drug from other anti HIV class were also combined such as protease inhibitors indinavir. This concept of three drug therapy was quickly adapted in to clinical practice this rapidly showed impressive benefit with 60-80% decline in rates of AIDS, death and hospitalization this is called HAART (highly active antiretroviral therapy.

21. HIV Life Cycle Step 1: Fusion Step 2: Transcription reverse transcriptase Step 3: Integration Step 4: Cleavage Step 5: Packaging and Budding HIV

22. Targets for treatment of HIV (anti-retroviral drugs

23. Nucleoside Reverse Transcriptase Inhibitors Zidovudine, Emtricitabine, Didanosine Are nucleoside & nucleotide analogues

24. Mechanism of action Selective reverse transcriptase inhibitors Acts as competitive substrate inhibitors Can also be incorporated into growing viral DNA chain and causes its termination

25. Zidovudine Pharmacokinetics Orally effective Penetrates CSF Excreted through kidney

26. Side effects Bone marrow depression (leukopenia) Headache Nausea, anorexia Myopathy, fatigue

27. Continue Can be used in children in low doses, during pregnancy & delivery

28. Emtricitabine Oral formulation should not be used in a pregnant AIDs patient because it contains a propylene glycol which is a potentially toxic compound for the fetus.

29. Continue Highly absorbed orally, not affected by food. Common adverse effects GIT upset Hyperpigmentation of palms& soles

30. Didanosine Oral bioavailability is reduced by food Eliminated by the kidney Causes acute pancreatitis as a side effect & retinal damage & Peripheral neuropathy

31. Therapeutic effects for all Increase T cells partially restoring immune system Reverses AIDS dementia

32. Non-Nucleoside Transcriptase Inhibitors Nevirapine ( 1 st generstion), Etravirine ( 2 nd generation )

33. Mechanism of action Bind near the active site of the viral reverse transcriptase to inhibit its activity ( Act as a non-competitive inhibitors of reverse transcriptase enzyme )

34. Pharmacokinetics Orally effective Metabolized in liver Excretion through kidney Inducer of hepatic cytochrome P450

35. Continue Very effective for prevention of transmission of infection as a single dose at time of labor and continue as an oral doses for 3 days for the neonates

36. Side Effects Hepatotoxicity Skin reaction up to life threating as Steven-Johnson Syndrome ( mainly with nevirapine) Diarrhea Headache

37. Protease Inhibitors Protease inhibitors Ritonavir, Atazanvir

38. Mechanism of action Block the viral protease enzyme necessary to produce mature virions ( prevent polyprotein cleavage,which is necessary for the maturation of viral cells )

39. Pharmacokinetics Atazanavir oral absorption requires an acid environment Excretion via biliary elimination Enzyme inhibitors P450

40. Pharmacokinetics Ritonavir Should be taken with meals ( its oral bioavailability increases with food ) Clearance is mainly via the liver Enzyme inhibitors P450

41. Side effects for protease inhibitors Increased bleeding in hemophilic patients Increased blood sugar level ( worsening of diabetes) Changes in body fat distribution central obesity, buffalo hump, (gynecomastia)

42. Dorsocervical fat pad (“buffalo hump’)

43. Entry Inhibitors Maraviroc Mechanism of action Blocks certain strains of HIV from binding to chemokine receptor type 5 ( CCR5) thus preventing the virus from entering target cells.

44. Continue If the patient,s virus is chemokine receptor type 4, the drug will not be effective. Cross CSF Excreted mostly through feces Well tolerated & few side effects

45. Thank You!