HIV medications Side Effects and Choices of Treatment

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

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

Entry inhibitors

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

Nucleoside/nucleotide reverse 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

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

� 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: HLAB 5701 � Can cause headaches � 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

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

� 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

� Viramune � 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 and occasional vivid dreams. Rarely they cause depression

� Isentress; most likely to cause diarrhea

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

� Tivicay; drug interactions, diarrhea

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

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

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

� Reyataz: 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

Blood tests for monitoring � Abacavir: HLA B 5701 genetic marker of allergic reaction

� Kidney function tests: creatinine and urinalysis, especially for patients on truvada or Viread 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 nonnucleosides

� 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)

� 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 A 1 c, glucose � Especially for patients on PI’s

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

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

� 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

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

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

Needs brain penetration � Kaletra/Combivir � Prezista/Norvir/Epzicom � Isentress/Epzicom

Clinical cases

#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?

#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?

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

#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?

#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?

#6 � 34 yo homeless man, new diagnosis of AIDS, severely anemic, +HLA B 5701, Cr 2. 3 (kidney damage), and severe MAC infection with CD 4 count <10 and HIV RNA PCR >100, 000 on admission

#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. CD 4 count <50, HIV viral load >100, 000 � How would you decide what, and when to change HIV meds?

#8 � 31 yo male, dx AIDS and MAC 6 months ago. Has tried multiple HIV meds. CD 4 count <10, HIV RNA PCR >100, 000 � Allergic to efavirenz, neviripine, intelence, abacavir, truvada, norvir, prezista, kaletra, lexiva, reyataz. � What drug cocktails can still be used?

Benefits of treatment

#9 � 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.

#10 � 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”.

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!