HIV medications: Side Effects and Choices of

TreatmentArdis Ann Moe, M.D.

UCLA CARE Clinic/NEVHC HIV Clinic Van Nuys.28 August 2015

amoe@mednet.ucla.edu

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

Objectives

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

Entry inhibitors

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

Liver problems fairly rare now with non-DDI, non-AZT nucs

Most common nucleotide backbone of most HIV cocktails (part of truvada)

Causes kidney damage Causes bone thinning Occasional GI upset Likely to be replaced with tenofovir

alafenamide (TAF)—TAF MUCH less toxic to kidneys and bone—likely out fall 2015.

Viread/tenofovir disoproxil (TDF)

Emtriva (part of truvada) Essentially as safe as Epivir, but more rash

Epivir likely the safest of all the nucs

Abacavir: as noted, an allergic reaction for persons with genetic trait: HLAB5701

Can cause headaches, nausea

Combination drug Epzicom can cause more nausea than either drug alone

AZT; Zidovudine: Anemia, low white cells, fatigue, headache, nausea. Muscle wasting: “AZT butt”

Facial wasting, fat loss on legs and arms

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, as in cases of needlestick injuries

Non nucleosides

As a class, they all cause rash and liver inflammation and have multiple drug interactions

Sustiva (part of Atripla) Causes depression, suicidality, panic

attacks, insomnia (interferes with REM sleep), vivid dreams, elevated cholesterol and triglycerides.

Not recommended for women in 1st trimester, or who are likely to become pregnant (US)

Sold on streets as alternative to LSD

Viramune/Neviripine Most likely to cause severe rash (Stevens

Johnson syndrome). Proper dosing when starting medication can make rash less likely

Intelence Vivid dreams, gritty taste

Edurant Some depression, some vivid dreams.

Integrase inhibitors

As a class they all cause diarrhea,gas, and occasional vivid dreams.

Rarely they cause depression

Isentress; most likely to cause diarrhea Low barrier to resistance; twice daily drug

increases risk of missing doses

Elvitegravir: gas, diarrhea. Has to be given with cobisistat so there will

be drug interactionslow barrier to resistance

Tivicay/dolutegravir; drug interactions, diarrhea

Somewhat higher barrier to resistance

Protease inhibitors

As a class they all cause diabetes and insulin resistance.

They all cause diarrhea and GI upset

The older drugs also raise cholesterol, triglycerides significantly (Crixivan, Invirase, Viracept, Kaletra) and can cause fat accumulation (lipodystrophy)

PI’s

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

Reyataz/atazanavir: can also cause yellow eyes (jaundice)

May cause confusion about liver function when patients have chronic hepatitis B or hepatitis C

Lexiva, Prezista have significant risk of skin rash

Prezista has the worse GI side effects of all the newer PI’s

Abacavir: HLA B5701 genetic marker of allergic reaction

Blood tests for monitoring

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

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

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) BUT only certain HIV cocktails are compatible with hep C treatments

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

Hemoglobin A1c, glucose Especially for patients on PI’s

Cholesterol, triglycerides◦ Especially for patients on atripla and PI’s

Plan A: “A pill A day for type A personalities” Atripla, Complera, Stribild, Triumeq◦ Low barrier to resistance (usually)◦ NOT for patients who are unreliable about

medications or appointments

Quick-and-dirty: Plans A,B,C and D

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 OR <200 CD4 cells at baseline

◦ Reyataz/norvir/truvada◦ Evotaz◦ Prezista/norvir/truvada◦ Prezcobix

High barriers to resistance. May aggravate diabetes Can substitute epzicom for truvada if there is kidney

damage(HLA B5701 neg only)

PI’s good for those on the brink….

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

Plan D: for Drug-drug interactions OR DARN I stuck myself/DARN I had sex

Isentress +truvada Has fewest drug interactions Preferred drugs for needlestick injuries or

PEP

Alternative cocktail for pregnant women with HIV

Diabetic:

Avoid PI’s if possible Avoid TDF if possible, given risk of kidney

damage with diabetes

Special cases

Kaletra/Combivir Prezista/Norvir/Epzicom Isentress/Epzicom Tivicay/Epzicom

Needs brain penetration

Avoid TDF

Check HLA B5701; if negative, then can use abacavir (part of Epzicom)

If HLA B5701 +, may need to use unusual cocktail to attend HIV control

Kidney disease

Best cocktails with hep C meds: isentress + truvada or epzicom, or tivcay + truvada or epzicom

Non nuc’s and boosted PI’s limit hep C treatment options (ok with declatisivir and sofosbuvir, however)

Hepatitis C

Clinical cases

32 yo homeless man, HIV+ new diagnosis. Alcoholic, depressed, Cr 2.3 (normal 1.2).

Hepatitis C. CD4 count 130. HIV viral load 300,000.

What drugs would you try to AVOID?

#1

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?

#2

31 yo woman with HIV and hepatitis B. She wants to get pregnant.

What drug should she avoid?What are good choices for her?

#3

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?

#4

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 would be his choices for HIV meds?

#5

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

#6

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?

#7

31 yo male, dx AIDS and MAC 6 months ago. Has tried multiple HIV meds.CD4 count <10, HIV RNA PCR >100,000

Allergic to efavirenz, neviripine, intelence, abacavir, truvada, norvir, prezista, kaletra, lexiva, reyataz.

What drugs can still be used?

#8

Benefits of treatment

24 yo MSM male, pre-med student, discovers he is HIV+

2 hours of counseling to prevent suicide in clinic

Later becomes a HIV testing counselor, a medical student, and then a successful physician.

Married, and now has adopted four children.

#9

AIDS patient in his 50’s, doing well, discovers that he is the only adult child willing to care for his demented evangelical homophobic minister father.

Dad moves into the apartment, overlooking the Gay Pride route in West Hollywood.

Dad looks out the window: “I think I hate those people but I forgot why”.

#10

Conclusions

Decide first if a patient is Plan A, B, C or D. Evaluate renal function, diabetes issues,

hepatitis, allergies, severity of HIV disease, mental illness.

Consider resistance issues and evaluate patient for ability to take medications.

Tailor HIV medications to patient’s profile Getting older also means getting revenge!