The HIV Diagnosis

The HIV Diagnosis Management of the HIV-infected patient in the primary care setting Lauren Pence, PharmD Ambulatory Care Clinical Pharmacy Specialist, Eskenazi Health Thursday, September 18, 2014 This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation

Objectives: • Identify the role of the primary care healthcare team in management of HIV patients • Describe how current antiretroviral medications inhibit the mechanism of infection of the HIV retrovirus • Develop a “checklist” for appropriate considerations in primary care patients with HIV • Identify common adverse effects of current antiretroviral medication

The HIV Diagnosis

SKIP IT • I feel comfortable with HIV management, and Jimmy John’s is delicious The HIV Diagnosis • You are a successful and cheerful pharmacist in 2014 • You attend a conference with a presentation on HIV infection in the primary care setting. There is a special at Jimmy John’s across the street and they are giving your favorite sandwich away for free. • What do you choose to do?

The HIV Diagnosis • Unfortunately, your friend who told you about this Jimmy John’s giveaway was mistaken, and it turns out they gave away free sandwiches yesterday. The store is closed and you get no lunch. • You return to your ambulatory care practice after the conference with a new patient with HIV on your physicians’ schedule. You forget the names of the HIV medications, but don’t have the handout to reference that was given at the lecture. You are hungry and sad. Here’s to better luck next time…

The HIV Diagnosis • You attend the presentation and learn a few new things about how to monitor HIV patients. • You return to your ambulatory care clinic after the conference with a new patient with HIV on one of your physicians’ schedule. You remember the adverse effects of the patients HAART regimen from the lecture, and recommend the appropriate labs. Your physician is very impressed with your HIV knowledge. Congratulations! Continue to the next adventure…

The “Chronic” HIV Infection Danish HIV cohort study - 2006 “By 2015, more than 50% of HIV-positive patients will be older than 50 years.” Atherosclerosis. 2011;219:384-389

CVD Death: MI/Ischemic: 3.2% Stroke: 1.4% Other: 3.3% Antiretroviral Cohort CollabortationClin Infect Dis. 2010;15;50(10):1387-96

Complications of HIV Infection Cardiovascular disease Neurocognitive disorders Dyslipidemia, metabolic abnormalities AIDS enteropathy Nephropathy Reduced bone mineral density Complications of HIV Infection: A Systems-Based Approach. American Family Physician. 2011:83:4

Mechanism of HIV Infection http://colgateimmunology.blogspot.com

FDA Approved Medications Nucleoside Reverse Transcriptase Inhibitors (NRTI) • Abacavir (ABC) • Didanosine (ddI) • Emtricitabine (FTC) • Lamivudine (3TC) • Stavudine (d4T) • Tenofovir (TDF) • Zidovudine (AZT,ZDV) Integrase Inhibitor • Raltegravir (RAL) • Elvitegravir (EVG)* • Dolutegravir (DOL) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) • Delaviridine (DLV) • Efavirenz (EFV) • Etravirine (ETR) • Nevirapine (NVP) • Rilpivirine (RPV) Fusion Inhibitor • Enfuvirtide (ENF) CCR5 Antagonist • Maraviroc (MVC) Protease Inhibitor (PI) • Atazanavir (ATV) • Darunavir (DRV) • Fosamprenavir (FPV) • Indinavir (IDV) • Lopinavir (LPV)* • Nelfinavir (NFV) • Ritonavir (RTV) • Saquinavir (SQV) • Tipranavir (TPV) www.aidsinfo.nih.gov. January 2014

Recommended Initial Regimens Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. DHHS

Nucleoside Reverse Transcriptase Inhibitors Advantages • Well tolerated medications • Minimal drug interactions • Once daily combination products Disadvantages: • Possible increase in cardiovascular events (ABC/3TC) • Tenofovir: potential for renal impairment, decreased BMD • Zidovudine: bone marrow suppression, GI intolerance • Abacavir (ABC) • Didanosine (ddI) • Emtricitabine (FTC) • Lamivudine (3TC) • Stavudine (d4T) • Tenofovir (TDF) • Zidovudine (AZT,ZDV)

Non-Nucleoside Reverse Transcriptase Inhibitors Advantages • Well tolerated medications • Minimal drug interactions Disadvantages: • Greater risk of resistance with treatment failure • Cross resistance potential • Serious skin rash • Rilpivirine - meal requirement • Efavirenz – teratogenicity, lipid abnormalities • Delaviridine (DLV) • Efavirenz (EFV) • Etravirine (ETR) • Nevirapine (NVP) • Rilpivirine (RPV)

Protease Inhibitors Advantages • Higher barrier to resistance Disadvantages: • Metabolic complications: • Dyslipidemia • Insulin resistance • Hepatotoxicity • GI adverse effects • Drug interactions • Strong CYP3A4 inhibitors • Atazanavir (ATV) • Darunavir (DRV) • Fosamprenavir (FPV) • Indinavir (IDV) • Lopinavir (LPV) • Nelfinavir (NFV) • Ritonavir (RTV) • Saquinavir (SQV) • Tipranavir (TPV)

Integrase Inhibitors Advantages: • Well tolerated medications • Fewer drug interactions Disadvantages: • Lower barrier to resistance • Newer agents = higher cost • Elvitegravirw/ cobicistat • Decreased CrCl • Drug interactions: CYP3A4 inhibitor • Raltegravir: rhabdomyolysis and hypersensitivity reactions • Integrase Inhibitor • Raltegravir (RAL) • Elvitegravir (EVG) • Dolutegravir (DOL)

YES • Initiate simvastatin 40 mg daily Patient Case: Cardiovascular Risk • 46 yo AA female with HIV, HTN, and tobacco dependence • HAART regimen of boosted darunavir/tenofovir/emtricitabine • ASCVD 10-year risk of 7.8%, LDL of 176 • Is a statin indicated in this patient? If so, what regimen would you initiate?

Patient Case: Cardiovascular Risk • Per the lipid guidelines, this patient qualifies for a moderate or high intensity statin. • However, it is recommended to start a lower dose of atorvastatin in patients also taking a protease inhibitor. • Your patient develops muscle aches and myalgias shortly after initiating treatment and stops therapy. Here’s to better luck next time…

Patient Case: Cardiovascular Risk • Per the lipid guidelines, this patient qualifies for a moderate or high intensity statin. • However, simvastatin is contraindicated in patients taking protease inhibitors. • Your patient develops muscle aches and myalgias shortly after initiating treatment and stops therapy. Here’s to better luck next time…

Patient Case: Cardiovascular Risk • Per the lipid guidelines, this patient qualifies for a moderate or high intensity statin. • The patient presents to your next visit in 3 months, and her LDL is 98. She has no complaints or concerns. Congratulations! Continue to the next adventure…

Statins and Antiretroviral Therapy Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. DHHS

YES • Initiate simvastatin 40 mg daily Patient Case: Cardiovascular Risk • 46 yo AA female with HIV, HTN, tobacco dependence • HAART regimen of boosted darunavir/tenofovir/emtricitabine • ASCVD 10-year risk of 7.8%, LDL of 176 • Is a statin indicated in this patient? If so, what regimen would you initiate?

Metabolic Abnormalities Diabetes Mellitus Dyslipidemia Risk factors: Traditional risk factors HIV infection itself ARVs: PIs, efavirenz Recommendations Screen: FLP prior and 1-3 months after ART Treat: according to lipid guidelines Drug interactions with some PIs/NRTIs and statins • Risk factors: • Traditional risk factors • HIV infection itself • Older PIs: nelfinavir, lopinavir Recommendations • Screen: HgA1c or fasting glucose prior and 1-3 months after ART • Treat: according to ADA guidelines Primary Care Guidelines for the Management of Persons Infected with HIV. Clin Infect Dis. 2013

H2RA • Initiate ranitidine 150 mg BID Patient Case: Heartburn • 54 yo AA male with HIV, type II DM, HTN, dyslipidemia • HAART regimen of boosted atazanavir/tenofovir/emtricitabine • Patients presents with symptoms of dyspepsia, heartburn • What acid suppressing agent would you start in this patient?

Patient Case: Heartburn • Absorption of boosted atazanavir can be decreased with simultaneous administration of PPIs. Therefore, PPIs are not recommended in PI-experienced patients • After prescribing your patient omeprazole 40 mg, the patient is not adequately absorbing his boosted atazanavir, leading to possible resistance. Here’s to better luck next time…

Patient Case: Heartburn • Absorption of boosted atazanavir can be decreased with administration of certain acid suppressing agents, if not administered at the appropriate time. • After prescribing your patient ranitidine 150 mg BID but not counseling him on the appropriate timing of the doses, the patient takes it inappropriately and is not adequately absorbing his boosted atazanavir, leading to possible resistance. Here’s to better luck next time…

Patient Case: Heartburn • If patient takes calcium carbonate simultaneously with boosted atazanavir, decreased atazanavir concentrations are expected • After prescribing your patient calcium carbonate but not counseling him on the appropriate timing of the doses, the patient takes it simultaneous with his HAART regimen and is not adequately absorbing his boosted atazanavir, leading to possible resistance. Here’s to better luck next time…

GI Complications Antiretrovirals with food requirement Antiretrovirals interacting with acid suppressants Atazanavir/ritonavir Antacid: 2 hr before or 1 hr after H2RA: Simultaneous or > 10 hr before PPIs not recommended in PI-experienced patients Rilpivirine Antacid: 2 hr before or 4 hr after H2RA: 12 hr before or 4 hr after PPIs contraindicated Elvitegravir Antacid: Separate by 2 hours • Efavirenz - empty stomach • Rilpivirine - at least 400 kcal • Atazanavir - with food • Ritonavir - with food

H2RA • Initiate ranitidine 150 mg BID Patient Case: Heartburn • 54 yo AA male with HIV, type II DM, HTN, dyslipidemia • HAART regimen of boosted atazanavir/tenofovir/emtricitabine • Patients presents with symptoms of dyspepsia, heartburn • What acid suppressing agent would you start in this patient?

NO • Prescribe combined oral contraceptive in addition to condoms Patient Case: Contraception • 28 yohispanic female with HIV, asthma • HAART regimen of efavirenz/tenofovir/emtricitabine • Patient states she is using condoms as her preferred birth control method, and states she does not want to conceive. • Is this an appropriate contraception regimen? What would you recommend as the most appropriate regimen?

Patient Case: Contraception • Condoms are recommended to prevent pregnancy, but also to decrease HIV and other sexually-transmitted infections • Recommendations encourage patients to use a secondary method of contraception to decrease the risk of unplanned pregnancy • Your patient is not currently using effective contraception, and is currently at risk for an unplanned pregnancy while on efavirenz, which is teratogenic. Here’s to better luck next time…

Patient Case: Contraception • A secondary type of contraception is recommended in addition to condoms. • Efavirenz decreases the concentrations of levornogestrel and norgestimate. • You choose a combined oral contraception product that does not interact with efavirenz, and your patient is adequately protected from unplanned pregnancy while on a teratogenic medication (efavirenz) Congratulations! Continue to the next adventure…

Patient Case: Contraception • A secondary type of contraception is recommended in addition to condoms. • Efavirenz does not interact with the depo-provera injection, however, both depo-provera and tenofovir run the risk of decreased bone mineral density • Your patient is adequately protected from unplanned pregnancy while on a teratogenic medication (efavirenz), however, suffers a right tibia fracture five years later. Here’s to better luck next time…

Contraception Recommendations: • Condom use: Contraception, STD protection, HIV transmission • Encourage second method of protection • Drug interactions with combined hormonal contraceptives • IUD use: Safe and effective. No increase in HIV viral shedding Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. DHHS

NO • Prescribe combined oral contraceptive in addition to condoms Patient Case: Contraception • 28 yohispanic female with HIV, asthma • HAART regimen of efavirenz/tenofovir/emtricitabine • Patient states she is using condoms as her preferred birth control method, and states she does not want to conceive. • Is this an appropriate contraception regimen? What would you recommend as the most appropriate regimen?

Osteoporosis • Risk factors: • HIV infection – as compared to individuals without HIV infection: • Increase in fracture rate by 30-70% • Three-fold increase in osteoporosis risk • Increase in Vitamin D deficiency prevalence of 60-75% • Antiretrovirals or uncontrolled viremia • Recommendations: • Screen: Baseline DXA scan should be completed in postmenopausal women and men aged > 50 years • Periodic monitoring thereafter – assess other risk factors • Treat: According to NOF guidelines: • Vitamin D and/or calcium supplementation • Bisphosphonate if indicated Primary Care Guidelines for the Management of Persons Infected with HIV. Clin Infect Dis. 2013

HIV Medication Interactions Resources • DHHS Treatment Guidelines • www.aidsinfo.nih.gov/guidelines • Database of antiretroviral drug interactions • http://hivinsite.ucsf.edu • HIV-drug interactions – University of Liverpool • www.hiv-druginteractions.org

YES • One dose of PCV13 today, then PPV23 in 5 years Patient Case: Vaccinations • 38 yocaucasian female with HIV, asthma, hyperlipidemia, HTN • HAART regimen of efavirenz/tenofovir/emtricitabine • CD4 count of 284 cells/mcL • PPV23 (Pneumovax) received 8/2/2011 • Does the patient require further pneumococcal vaccination?

Patient Case: Vaccination • Patients with HIV are eligible for all vaccinations if the CD4 count is > 200 cells/mcL • Without further vaccinations, this patient is not appropriately immunized and is at risk for pneumococcal infection. Here’s to better luck next time…

Patient Case: Vaccination • After receiving the PCV13 vaccination today, the patient is appropriately immunized against pneumococcal infection. • The patient receives the second dose of PPV23 in five years, and does not develop pneumonia. Congratulations! Continue to the next adventure…

Patient Case: Vaccination • It is recommended that this patient receive a dose of PCV13 one year after the original PPV23 vaccination, prior to revaccination with PPV23 in 5 years. • Without the PCV13 vaccination, this patient is not appropriately immunized and is at risk for pneumococcal infection. Here’s to better luck next time…

Pneumococcal Vaccination • If no previous pneumococcal vaccination: • If previous pneumococcal vaccination:

Vaccinations Adapted from the Advisory Committee on Immunization Practices (ACIP) 2013 Adult Immunization Schedule

NO • OI prophylaxis not indicated until CD4 count < 100 cells/mcL Patient Case: Opportunistic Infection (OI) • 32 yocaucasian male with HIV, Type II DM, HTN, GERD • Newly diagnosed with HIV • HAART regimen of efavirenz/tenofovir/emtricitabine • CD4 count of 184 cells/mcL, viral load of 19,438 copies/mL • Does this patient require prophylaxis for an OI?

Patient Case: Opportunistic Infection (OI) • This patient begins taking one TMP/SMX DS tablet daily per your request. • The patient is appropriately protected against pneumocystisjirovecci pneumonia Congratulations! Continue to the next adventure…

Patient Case: Opportunistic Infection (OI) • Opportunistic infection prophylaxis is indicated after CD4 count decreases below 200 cells/mcL • The patient is not appropriately protected against pneumocystisjirovecci pneumonia Here’s to better luck next time…

Patient Case: Opportunistic Infection (OI) • This patient begins taking one TMP/SMX DS tablet daily per your request. • The patient is appropriately protected against pneumocystisjirovecci pneumonia. However, the itraconazole is not indicated until CD4 count decreases below 150 cells/mcL. • The patient experiences significant nausea, to which he stops both the TMP/SMX DS and itraconazole 10 days after initiation. Here’s to better luck next time…

The HIV Diagnosis