Overview of ARV Drug Classes and Individual Drugs

1. Overview of ARV Drug Classes and Individual Drugs Ardis Ann Moe, M.D. amoe@mednet.ucla.eduUCLA CARE clinic/NEVHC Van Nuys HIV Clinic 29 August 2014

3. Goals: • 1)to understand the differences between the four major drug classes of HIV medications • 2)Issues on how to obtain medications • 3)Issues on different formulations of HIV meds (liquid, injection, tablet, gel, etc)

4. Major drug classes

6. Entry inhibitors

7. Two major forms: • Maraviroc (Selzentry), a twice daily oral medication • Envirfiratide (Fuzeon), a twice daily injected medication

8. Maraviroc (Selzentry) • Twice daily oral medication • Acts as a “condom for the CD4 cell” • Blocks the attachment of the HIV virus to one of the proteins on the surface of the CD4 cell—the CCR5 attachment receptor protein

9. Maraviroc (Selzentry) requires an expensive blood test “Trofile” in order to determine if the medication will work. • Some patients have strains of HIV virus that do NOT attach to the CCR5 protein, and so are resistant to Maraviroc.

10. The blood test costs $2,000 or more, often requires prior authorization, and is available from ADAP with a rationed system of coupons • In addition, the patient has to have a viral load of >1,000 in order for the usual “trofile” test to be valid. • A specialized form of the “trofile”can be used in patients with <1,000 copies

11. The drug itself is quite well tolerated; the only real problem is the trofile test • Most insurance companies or ADAP will not pay for maraviroc unless a trofile is done and it indicates that maraviroc will work.

12. Enfuvirtide (T-20) or Fuzeon • Injectable drug, twice daily. • Essentially doubles the cost of HIV treatment • Rarely used; less potent than most other available HIV medications • “condom for the HIV virus” • Prevents the HIV virus from attaching to the CD4 cell by blocking the attachment of the gp41 protein of the HIV virus to the CD4 cell.

13. Major value of Fuzeon is that it has essentially no drug interactions, and can be given as an injection.

15. Reverse Transcriptase inhibitors, nucleosides/nucleotide

16. AZT (zidovudine). The first HIV drug. Licensed in 1987 • As monotherapy, AZT drops HIV viral load approx 50% for a few months • Available as pills, IV, and liquid forms. generic • Transformed the future for pregnant women with HIV. AZT monotherapy dropped transmission from 25% to 8% in PAETC 076 • Excellent brain tissue penetration

17. CONCORD study (1994) indicated that AZT monotherapy did not improve survival beyond the first year of therapy. • Initial doses of AZT were 3x what are used now.

18. DDI (Videx) didanosine • Second drug approved to treat HIV • Most dangerous drug in the whole armamentarium because of side effects • Cheap, available on PEPFAR formularies • Powder forms; tablet. Once daily. generic • Has to be taken on an empty stomach

19. Tenofovir (Viread) Part of Truvada • Nucleotide RT • One of the most common HIV meds used worldwide • Once daily pill or pediatric powder; also treats hepatitis B • As part of PREP, also has some prevention of HSV-2 • Poor brain tissue penetration

20. Lamivudine/emtricitabine • Epivir /emtriva • Available in pill, liquid forms. Lamivudine generic • Both treat hepatitis B • Emtriva is a part of Truvada • Lamivudine is part of Epzicom

21. Abacavir (Ziagen) part of Epzicom • Available in pill and liquid forms; generic • Can cause a severe allergic reaction in persons who have genetic predisposition • Needs HLAB5701 blood test before use of medication • Good brain tissue penetration

22. Stavudine (Zerit) • Rarely used because of long term side effects • “bridge” drug for short term use; • fair/poor brain tissue penetration • Pill and liquid forms; generic available. • Can not be given in combination with AZT because of intracellular antagonism, and cannot be combined with Videx because of synergistic toxicity

23. Combination drugs: • Trizivir (AZT/Epivir/Ziagen) • Epzicom (Epivir/Ziagen) • Truvada (Viread/Emtriva)

24. In general, Trizivir not adequate treatment for HIV infection for newly diagnosed HIV+ persons. • Triple therapy with all-nuceloside cocktails have suboptimal potency

25. Non-nuclosides

27. As a class the non-nucs have multiple drug interactions, esp with seizure medications, cardiac medications, methadone, etc.

28. Non-nucleoside RT inhibitors act on the RT enzyme directly; nucleoside RT inhibitors act on the growing DNA chain, inserting themselves as false pieces into the growing DNA chain.

30. Neviripine (Viramune) • Available as pill and liquid forms • Safe in pregnancy, penetrates brain tissue well • Twice or once daily • Viramune XR more expensive; many insurance companies will only pay for generic neviripine

31. Delavirdine (Rescriptor) • Rarely used because of large pill counts

32. Efavirenz (Sustiva) part of Atripla • Once daily; tabs or caps, taken on an empty stomach • Capsules can be opened up and sprinkled as a powder • Good penetration into brain tissue BUT can reduce memory because of more depression

33. Rilpivirine (Edurant) Part of Complera • “Sustiva” jr. • Less potent, less side effects • Is taken with food. • Tablet only (small tablet—25 mg)

34. Etravirine (Intelence) • Twice daily, useful as salvage if a patient has resistance to Sustiva or Edurant or Viramune. • Tablet form only; but does dissolve in water • Good penetration into brain tissue • Gritty taste

35. Integrase inhibitors

37. Raltegravir (Isentress) • Twice daily tablet. Has the advantage of relatively few drug interactions. • Once daily dosing is less effective. • Good penetration into brain tissue

38. Elvitregravir. Available currently only as part of Stribild • Needs boosting agent to work: cobisistat (part of Stribild) • Drug interactions • Once daily tablet form

39. Dolutegravir (Tivicay) Part of Triumeq • Once daily for HIV treatment naïve; twice daily as salvage treatment. • Small tablets • Drug interactions • Good penetration into brain tissue

40. Protease inhibitors

42. As a class, protease inhibitors were the linchpin of HIV cocktails. When the first PI’s were approved in 1996 and were used in combination with the older nucelosides, there was a revolution in the treatment of HIV • PI’s still have the best data on treating severely ill AIDS patients with AIDS cancers and OI’s.

44. In general, PI’s have many drug interactions, esp with cardiac medications, methadone, seizure medications, and coumadin (warfarin)

45. Ritonavir (Norvir). • One of the first PI’s • Now used as boosting agent; ritonavir combined with other PI drugs to make them more effective by raising blood levels of the other PI drugs. • Capsule, liquid (vile), and tablet form • Usually dosed as 1 or 2 tablets once daily

47. Ritonavir blocks first pass effect, so less drugs are needed less often. • Once-daily dosing possible with PI’s • Also sold on streets to make heroin, meth, and viagra more effective

48. Indinavir (Crixivan) • One of earliest PI’s; now rarely used because of side effects • Best taken with ritonavir for boosting effect • Tablet form only

49. Saquinavir (Invirase) • Tablet and capsule form • Best used with ritonavir for boosting effect • Now rarely used because of side effects

50. Nelfinavir (Viracept) • Tablet and powder form • Only PI currently in use that does NOT use ritonavir • Less effective than other boosted PI’s • Safe in pregnancy • Poor penetration into brain tissue