1. Ardis Ann Moe, M.D. amoe@mednet.ucla.edu amoe@mednet.ucla.edu UCLA CARE clinic/NEVHC Van Nuys HIV Clinic 28 August 2015

3.  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

5.  1)entry inhibitors  2)reverse transcriptase inhibitors (nucloside and non-nucleoside)  3)integrase inhibitors  4)protease inhibitors

8.  Two major forms: ◦ Maraviroc (Selzentry), a twice daily oral medication ◦ Envirfiratide (Fuzeon), a twice daily injected medication

9.  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

10.  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.

11.  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

12.  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.

13.  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.

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

17.  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

18.  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.

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

20.  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

21.  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

22.  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

23.  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

24.  Combination drugs:  Trizivir (AZT/Epivir/Ziagen)  Epzicom (Epivir/Ziagen)  Truvada (Viread/Emtriva)

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

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

29.  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.

31.  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

32.  Delavirdine (Rescriptor)  Rarely used because of large pill counts

33.  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

34.  Rilpivirine (Edurant) Part of Complera  “Sustiva” jr. ◦ Less potent, less side effects ◦ Is taken with food. ◦ Tablet only (small tablet—25 mg) ◦ Useful in patients with low initial HIV viral loads who insist on small pills

35.  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

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

39.  Elvitregravir.  Needs boosting agent to work: cobisistat (drug interactions)  Once daily tablet form

40.  Dolutegravir (Tivicay)  Once daily for HIV treatment naïve; twice daily as salvage treatment.  Small tablets  Drug interactions  Good penetration into brain tissue

43.  When the first PI’s were approved in 1996 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.

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

46.  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

48.  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

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

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

51.  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

52.  Lopinavir/ritonavir (Kaletra)  Combination drug of 2 PI’s; ritonavir used only for boosting.  Liquid (vile) and tablet form.  Better tolerated as 2 tabs twice daily with food. Good penetration to brain tissue  Best safety data in pregnancy. Used in combination with AZT/lamivudine

53.  Atazanavir (Reyataz)  Once daily dosing, taken with ritonavir 1 a day OR with cobisistat as combo drug: Evotaz  Tablet and oral powder form  Drug interaction with heartburn meds  Penetrates brain tissue poorly

54.  Fos-amprenavir (Lexiva)  2 tabs once a day, used with ritonavir.  Liquid, tablet forms available  Can be taken with heartburn medications  Good penetration to brain tissue

55. Tipranavir (Aptivus) Rarely used because of high pill count (2 pills twice daily + 1 ritonavir twice daily)

56.  Darunavir (Prezista)  Tablet and liquid forms  Once daily with 1 ritonavir for initial therapy; twice daily with 1 ritonavir twice daily for salvage therapy  Combo drug with cobisistat: Prezcobix  Can be used as initial or salvage therapy  Can be taken with heartburn meds  Good penetration to brain tissue

57.  59 yo male  HIV RNA PCR <20 copies, CD4 count 400’s on Reyataz, Norvir, truvada.  Worsening memory loss

58.  42 yo male  New diagnosis of AIDS and lymphoma of esophagus (AIDS cancer). Needs large doses of heartburn medications  Cannot swallow pills.

59.  25 yo female from Kenya; here for treatment of acid burns (Grossman Burn Foundation). On complera (rilpirivine/emtricitabine/viread) but will be going back to Kenya in November. HIV viral load undetectable and CD4 count 400.

61.  Multiple HIV medications, and multiple different combinations.  Drug interactions, generic vs brand drugs, formulations are issues in what drug is used.  Maturation inhibitors, more entry inhibitors being developed