Exploring HIV in 2017: What a pharmacist needs to know

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Sibyl Knight
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1 Exploring HIV in 2017: What a pharmacist needs to know Lifecycle of the HIV virus a. HIV spread through mucous membrane contact, damaged tissue contact, or blood contact with: blood, semen, rectal fluids, vaginal fluids, breast milk i. High risk activities: anal or vaginal sex with HIV+ partner without a condom, sharing needles or syringes with HIV+ person ii. Other bodily fluids not considered infectious UNLESS visibly bloody 1. ALWAYS follow universal precautions b. HIV infects the CD4 T-lymphocyte- General in command of the immune system c. Virologic lifecycle: i. key steps in HIV virologic life cycle 1. fusion and entry- HIV binds the CD4 protein and uses either CCR5 or CXCR4 to enter the cell a. fusion and entry inhibitors 2. reverse transcription- HIV RNA is reverse transcribed into HIV viral DNA a. nucleoside reverse transcriptase inhibitors b. non-nucleoside reverse transcriptase inhibitors 3. integration- HIV viral DNA is integrated into the host CD4 T-cell s DNA a. integrase strand transfer inhibitors 4. maturation and assembly- new HIV viral RNA is packaged and the final viral particle is assembled a. protease inhibitors

2 Current medications used to treat HIV: Nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disproxil fumarate (TDF) tenovofir alafenamide (TAF) abacavir (ABC) lamivudine (3TC) emtricitabine (FTC) zidovudine (AZT) - start up syndrome diarrhea, lethargy -abacavir- risk for fatal hypersensitivity-> must be HLA-B5701 negative -tenofovir disproxil fumarate- renal toxicity and loss of bone mineral density TDF AUC may be increased by ledipasvir/sofosbuvir (Harvoni) -Intermediate barrier to -typically the backbone of a regimen due to few side effects and drug Brand name co-formulated drug combinations: -Truvada- tenofovir disproxil fumarate/emtricitabine (2016 preferred regimen with RTG, DTG, or DRV/RTV) -Epzicom- abacavir/lamivudine -Descovy- tenofovir alafenamide/emtricitabine (2016 preferred regimen with RTG, DTG, or DRV/RTV) -Stribild- tenofovir disproxil fumarte/emtricitabine/elvitegravir/cobicistat -Genvoya- tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat -Triumeq- abacavir/lamivudine/dolutegravir -Atripla- tenofovir disproxil fumarate/emtricitabine/efavirenz -Complera- tenofovir disproxil fumarate/emtricitabine/rilpivirine -Odefsey- tenofovir alafenamide/emtricitabine/rilpivirine Non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz (EFV) rilpivirine (RPV) etravirine (ETR) nevirapine (NVP) -efavirenzneuropsychiatric effects, vivid dreams, worsening depression -rilpivirine- only use if VL<100,000 and CD4 >200 cells/ml -nevirapinehepatotoxicity -Atripla- tenofovir disproxil fumarate/emtricitabine/efavirenz -Complera- tenofovir disproxil fumarate/emtricitabine/rilpivirine -Odefsey- tenofovir alafenamide/emtricitabine/rilpivirine -Sustiva- efavirenz -Intelence- etravirine -Viramune- nevirapine -Edurant- rilpivirine -efavirenz and nevirapine: CYP2B6 and CYP3A4 inducers-ex: Harvoni, methadone, oral contraceptives, statins, CCBs, warfarin, -etravirine- inhibits CYP2C9 and CYP2C19- ex: warfarin, clopidogrel, phenobarbital, phenytoin -rilpivirinecontraindicated with PPIs, H2RAs, antacids -Lowest barrier to -efavirenz- has long halflife->must give TDF/FTC for 2 weeks if discontinuing Atripla to prevent

3 Integrase strand transfer inhibitors (INSTIs) raltegravir (RTG) elvitegravir (EVG) dolutegravir (DTG) cobicistat (COBI) - start up syndrome diarrhea, lethargy -dolutegravir and cobicistat- blocks tubular secretion of creatinine (watch for non-pathological increase in SCr of mg/dl) -Stribild- tenofovir disproxil fumarte/emtricitabine/elvitegravir/cobicistat -Genvoya- tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat -Triumeq- abacavir/lamivudine/dolutegravir -Isentress- raltegravir -Tivicay- dolutegravir Protease inhibitors (PIs) darunavir (DRV) atazanavir (ATV) lopinavir (LPV) ritonavir (RTV) Prezista- darunavir Reyataz- atazanavir Norvir- ritonavir Kaletra- lopinavir/ritonavir Prezcobix- darunavir/cobicistat Evotaz- atazanavir/cobicistat -ALL INSTIs must be separated from polyvalent cations by at least 2-4 hours -raltegravir-ppis -dolutegravirmetformin, phenytoin, midazolam -elvitegravir/cobicistatcobicistat is a potent CYP3A4 inhibitor-> CONTRAINDICATED with atorvastatin, simvastatin, lovastatin, inhaled/intranasal corticosteroids and USE WITH CAUTION with warfarin, SSRIs, TCAs, CCBs, BDZs, methadone -GI intolerance ( diarrhea) lipodystrophy, lipid abnormalities, insulin -atazanavir-jaundice, sclera icterus, hyperbilirubinemia -ritonavir-nausea, vomiting, diarrhea, increased cholesterol and triglycerides -lopinavir-persistent diarrhea -elvitegravir-must be boosted by either cobicistat or ritonavir -raltegravir and elvitegravir intermediate barrier to -dolutegravir-high barrier to (2016 preferred regimen with TDF/FTC or TAF/FTC) (2016 preferred regimen with TDF/FTC or TAF/FTC) -ritonavir is a potent CYP3A4 inhibitor-> CONTRAINDICATED with atorvastatin, simvastatin, lovastatin, inhaled/intranasal corticosteroids and USE WITH CAUTION with warfarin, SSRIs, TCAs, CCBs, BDZs, methadone -atazanavir- limit PPIs to no more than omeprazole 20mg daily, separate out from H2RAs and antacids by at least 6-12hrs -ALL PIs must be boosted by ritonavir or cobicistat -exception is atazanavir which can be used unboosted in some cases -protease inhibitors have the highest barrier to -darunavir- is a sulfonamide->can use if patient had sulfa rash but avoid if patient had anaphylactic reaction to sulfonamides (2016 preferred regimen with RTV and either TDF/FTC or TAF/FTC) (2016 preferred regimen with DRV and either TDF/FTC or TAF/FTC)

4 CCR5 antagonist maraviroc (MVC) -fever, rash, cough -CYP3A4 substrate- >reduce dose to 150mg twice daily when used with ritonavir or cobicistat Selzentry -maraviroc Entry inhibitor enfuvitide (ENF or T20) Fuzeon-enfuvirtide Class side Effects Class drug -fatigue, insomnia, diarrhea, nausea, injection site reactions none additional -HIV must be tested to ensure it is R5 tropic and uses CCR5 to enter the CD4 cell -dual or mixed tropic virus means maraviroc will not work -usually only used for salvage in cases of -twice daily subcutaneous injection -only used for salvage in cases of Pre-exposure prophylaxis (PrEP) -tenofovir disproxil fumarate/emtricitabine (Truvada)- one tablet once daily to PREVENT HIV infection Indicated for: Protocol and Labs considerations -men who have sex with men (MSM) -injection drug users -people who exchange sex for money or goods -HIV serodiscordant couples in which the positive partner does not have a suppressed viral load -HIV serodiscordant couples who wish to conceive children -patients must have negative 4 th generation HIV test every 90 days to be on PrEP -prescriptions may only be written for up to 90 days at a time to ensure patients get their HIV test -STI screening at baseline and then every 3-6 months based on risk and provider discretion -CBC, CMP, Hepatitis serology at baseline and then every 6-12 months -over 90% effective in patients with perfect adherence (number needed to treat is 13) -TDF/FTC also used to treat Hepatitis B-> use with caution in patients with Hepatitis B infection due to risk of disease flare upon discontinuation -chances of acquiring resistant HIV virus very small but possible -PrEP often offered to people with positive STI screenings Post-exposure prophylaxis (PEP) -tenofovir disproxil fumarate/emtricitabine (Truvada) with either raltegravir (Isentress) or dolutegravir (Tivicay)- started within 72 hours of exposure and continued for 28 days following the exposure Indicated for: Protocol and Labs considerations -exposure to mucous membrane contact, damaged tissue contact, or blood contact with blood, semen, rectal fluids, vaginal fluids, breast milk from people with HIV infection or at high risk of HIV infection including MSM, people who exchange sex for money or goods, or IV drug users -MUST be initiated within 72 hours of exposure -4 th generation HIV-blood test at baseline, 6 weeks, and 4 months following exposure -STI screening, CBC, CMP, Hepatitis serology at baseline -referral to counseling, crisis services, or law enforcement if appropriate -consult an infectious disease specialist if patient infected with Hepatitis B -transition to PrEP for patients who are candidates or have repeated exposures requiring PEP

5 Vaccines in the HIV-positive patient Inactivated vaccines -Inactivated trivalent and quadrivalent influenza vaccines recommended at all CD4 counts -Hepatitis B vaccine recommended at all CD4 counts -most effective if CD4 above 350 cells/ml -Meningococcal ACWY vaccine recommended for all people living with HIV -Serotype B vaccine still only recommended for at risk groups (dormitories, barracks, rescue mission, etc.) -Pneumococcal vaccine is recommended -PCV13 (Prevnar13)- indicated for patients who have never had a pneumococcal vaccine or CD4 less than 200 cells/ml -PPSV23 (Pneumovax)- indicated for patients vaccinated with PCV13 over 8 weeks ago or patients vaccinated with PPSV23 5 or more years ago Live attenuated vaccines -Zoster (Zostavax) recommended for patients with CD4 counts greater than 200 cells/ml and over 60 years old -Varicella- recommended on a case by case basis for high risk patients -HPV- recommended on a case by case basis for high risk patients -MMR-recommended on a case by case basis for high risk patients -Hib- recommended on a case by case basis for high risk patients Note: if in doubt, request a prescription from the patient s HIV specialist for any live attenuated vaccines -Tdap is recommended at all CD4 counts -revaccinated every 10 years like normal resources: NW AIDS Education Training Center- NW AETC Project ECHO- weekly didactic lecture and case conference via telehealth HIV Web Study- self study course with CME Hepatitis Web Study- self study course with CME DHHS HIV Treatment Guidelines- International Antiviral Society (IAS-USA)- Contact information: Geoff L Heureux, PharmD, AAHIVP HIV Alliance-hivalliance.org 1966 Garden Ave, Eugene, OR Phone: (541) glheureux@hivalliance.org

HIV Management Update 2015

9/30/15 HIV Management Update 2015 Larry Pineda, PharmD, PhC, BCPS Visiting Assistant Professor Pharmacy Practice and Administrative Science ljpineda@salud.unm.edu Pharmacist Learning Objectives Describe