Ardis 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 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 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. 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 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. 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 interactions low barrier to resistance Tivicay/dolutegravir; drug interactions, diarrhea Somewhat higher barrier to resistance 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) 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 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 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) 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 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) 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 Kaletra/Combivir Prezista/Norvir/Epzicom Isentress/Epzicom Tivicay/Epzicom 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 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) 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? 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? 31 yo woman with HIV and hepatitis B. She wants to get pregnant. What drug should she avoid? What are good choices for her? 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? 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? 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 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? 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? 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. 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”. 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!