HIV medications: Side Effects and Choices of Treatment

1. HIV medications: Side Effects and Choices of Treatment Ardis Ann Moe, M.D. UCLA CARE Clinic/NEVHC HIV Clinic Van Nuys. 29 August 2014 amoe@mednet.ucla.edu

2. Objectives • To describe the major side effects of HIV treatment • To know useful lab tests for HIV side effect monitoring • To review case studies of how to choose initial HIV regimen, and what regimen to switch to in the event of side effects • Benefits of treatment

3. Entry inhibitors

4. Entry inhibitors • Fuzeon causes painful lumps on the skin that persist for weeks • Shots need to be done twice daily • Selzentry rarely causes rash; can cause orthostatic hypotension, nausea, dizziness. Cannot be used in kidney failure

5. Nucleoside/nucleotidereverse transcriptase inhibitors As a class, they are associated with liver problems: lactic acidosis, fatty liver disease Pancreatitis—rare in most of the nucs, common in Videx and Zerit

6. Viread/tenofovir • Most common nucleotide backbone of most HIV cocktails (part of truvada) • Causes kidney damage • Causes bone thinning • Occasional GI upset

7. Emtriva (part of truvada) • Essentially as safe as Epivir, but more rash • Epivir likely the safest of all the nucs

8. Abacavir: as noted, an allergic reaction for persons with genetic trait: HLAB5701 • Can cause headaches • Combination drug Epzicom can cause more nausea than either drug alone

9. AZT; Zidovudine: Anemia, low white cells, fatigue, headache, nausea. Muscle wasting: “AZT butt” • Facial wasting, fat loss on legs and arms

12. Stavudine (Zerit) • Neuropathy, facial wasting, fat loss in legs and arms. • Side effects start after 5 months or more of use—can be used as a “bridge” drug

13. Non nucleosides As a class, they all cause rash and liver inflammation

14. Sustiva (part of Atripla) • Causes depression, suicidality, panic attacks, insomnia (interferes with REM sleep), vivid dreams, elevated cholesterol and triglycerides. • Controversy on whether it causes birth defects • Sold on streets as alternative to LSD

15. Viramune • Most likely to cause severe rash (Stevens Johnson syndrome). Proper dosing when starting medication can make rash less likely

16. Intelence • Vivid dreams, gritty taste

17. Edurant • Some depression, some vivid dreams.

18. Integrase inhibitors As a class they all cause diarrhea and occasional vivid dreams. Rarely they cause depression

19. Isentress; most likely to cause diarrhea

20. Elvitegravir; as part of Stribild, has drug interactions and risk of kidney and bone damage. Also causes diarrhea

21. Tivicay; drug interactions, diarrhea

22. Protease inhibitors As a class they all cause diabetes and insulin resistance. They all cause diarrhea and GI upset

23. PI’s • The older drugs also raise cholesterol, triglycerides significantly (Crixivan, Invirase, Viracept, Kaletra) and can cause fat accumulation (lipodystrophy)

26. For older drugs, risk of lipodystrophy 75% after 2 years of use. Approx 5% for newer PI’s

27. Reyataz: can also cause yellow eyes (jaundice) • May cause confusion about liver function when patients have chronic hepatitis B or hepatitis C

29. Lexiva, Prezista have significant risk of skin rash • Prezista has the worse GI side effects of all the newer PI’s

30. Blood tests for monitoring • Abacavir: HLA B5701 genetic marker of allergic reaction

31. Kidney function tests: creatinine and urinalysis, especially for patients on truvada or Viread containing regimens

32. Liver function tests: • Bilirubin (jaundice test) usually around 2-3 in persons on reyataz. If >3.5 then alternatives to reyataz should be used • ALT, AST especially for patients on non- nucleosides

33. Note that hepatitis B usually gets better on certain HIV medications (Viread, truvada, Epivir, Emtriva) • Hepatitis C can get better on any effective HIV cocktail. (note jaundice risk with reyataz)

34. CBC with platelets and differential • Low platelets (bleeding risk) can improve within a few days of starting an effective HIV drug regimen • AZT can initially worsen, and then improve anemia • AZT can cause low white cells especially in patient with advanced AIDS

35. Hemoglobin A1c, glucose • Especially for patients on PI’s

36. Cholesterol, triglycerides • Especially for patients on atripla and PI’s

37. Quick-and-dirty: Plans A,B,C and D • Plan A: “A pill A day for type A personalities” Atripla, Complera, Stribild, Triumeq • Low barrier to resistance • NOT for patients who are unreliable about medications or appointments

38. Plan B: “Boosted protease inhibitor for batty buddies on the brink” • Most useful when you have patients with OI or AIDS cancers OR mentally ill patients OR patients with other adherence risks • Reyataz/norvir/truvada • Prezista/norvir/truvada • High barriers to resistance. • May aggravate diabetes • Can substitute epzicom for truvada if there is kidney damage

39. Plan C: “Curses, I forgot the Contraception” • Kaletra and Combivir (AZT/epivir) • First choice for pregnant women with HIV

40. Plan D: for Drug-drug interactions OR DARN I stuck myself • Isentress +truvada • Has fewest drug interactions • Preferred drugs for needlestick injuries

41. Special cases • Diabetic: • Triumeq (dolutegravir/lamivudine/abacavir) • Stribild • Atripla • Complera • Isentress/truvada • Recall that the above 4 cocktails all contain tenofovir, which can damage kidneys

42. Needs brain penetration • Kaletra/Combivir • Prezista/Norvir/Epzicom • Isentress/Epzicom

43. Clinical cases

44. #1 • 32 yo homeless man, HIV+ new diagnosis. • Alcoholic, depressed, Cr 2.3 (normal 1.2). Hepatitis C. • What drugs would you try to AVOID. • What initial labs do you need to make a drug choice decision?

45. #2 • 65 yo male new dx of HIV infection. • Hx of cardiac disease. On amiroidarone and warfarin (coumadin).normal kidney function • Takes medications regularly • What HIV medications do you need to AVOID? • What drug cocktails can be used in him?

46. #3 • 31 yo pregnant woman with HIV and hepatitis C. • What are her best choices of HIV meds?

47. #4 • 45 yo male, new dx of HIV. • Bad heartburn, has to take twice daily protonix. Reliable on taking meds • Diabetic, on insulin • What HIV meds should he AVOID? • What cocktails can he use?

48. #5 • 23 yo male with HIV, on atripla for 2 years. Has creatinine increased from 1.2 to 1.5 in the past 6 months. Chronic depression, insomnia. • What other tests do you need to perform in order to change meds? • What other questions do you need to ask before changing meds? • What would be his choices for HIV meds?

49. #6 • 34 yo homeless man, new diagnosis of AIDS, severely anemic, +HLA B5701, Cr 2.3 (kidney damage), and severe MAC infection with CD4 count <10 and HIV RNA PCR >100,000 on admission

50. #7 • 55 yo female with AIDS and CMV retinitis, going blind with syphilis. Homeless, cocaine addict. Normal Cr. Resistant to truvada and reyataz and norvir. CD4 count <50, HIV viral load >100,000 • How would you decide what, and when to change HIV meds?