HIV Pathology and ART Basics A Review for Non-Prescribing Clinical Staff

HIV Pathology and ART Basics A Review for Non-Prescribing Clinical Staff Dr. Brent J. Pimentel, MD/MPH Texas Program Manager South Central AETC Parkland Health & Hospital System Dallas, TX 1

Objectives Review the basics about HIV Infection, diagnosis and management Present the 6 types of meds used to treat HIV and common side effects Review Ryan White legislation and new techniques for prevention of HIV 2

OBJECTIVE 1 Review the Basics about HIV Infection, Diagnosis, and Management 3

AIDS ART CDC HIV OI Acronyms Acquired Immunodeficiency Syndrome Anti-Retroviral Therapy Centers for Disease Control Human Immunodeficiency Virus Opportunistic Infection 4

Immune Response Basics Immune Response triggered by Presence of Not-Host Agent Infectious: Bacteria, Virus, Parasites, etc. Environmental: Fungal, Pollen, etc. Other: Cancer, Foreign Body, etc. Once triggered, Network of Cells, Proteins, & Enzymes combine to Eliminate Agent Identification of Agent as Not-Host and Production of Specific Antibodies Antibodies bind irreversibly to Agent marking Not-Host Not-Host destroyed and remaining debris removed by network 5

HIV & the Immune Response Main Cell Line involved are the White Blood Cells (WBCs) or Leukocytes CD4 or Helper T Cells: the General of the Network CD8 or Killer/Cytotoxic T Cells: the Army of the Network HIV targets CD4 Cells and transforms them into virus-replication factories Regular CD4 Function ceases completely Identification of Not-Host and Antibody Production decreases Immune Response Progressively Weakens Over time, common Non-Host Agents likely to cause severe health issues 6

Transmission of HIV Infection Two Broad Categories for HIV HIV-1: Most Common in USA and Europe HIV-2: Most Common in Africa and Less Susceptible to Current Medications Virus found in ALL Body Fluids Infection Occurs through Fluid to Fluid Contact Must have Threshold Level of Virus in Infected Fluid for Transmission High Levels found in Blood, Semen, Vaginal Fluid, and Breast Milk Very Low / NON-infectious Levels found in Tears, Sweat, and Saliva Variable Levels found in Cerebrospinal Fluid 7

Diagnosis of HIV Infection Three Main Types of Testing for HIV Nucleic Acid Tests (NATs) Can detect infection in 7 to 28 Days but expensive and not used for routine screening Combination Antigen/Antibody Tests Can detect infection in 2 to 6 Weeks Detects both the actual HIV virus and the antibodies produced by the immune response Antibody Tests Can detect infection in 3 to 12 Weeks Detects the antibodies produced by the immune response to HIV infection 8

HIV-Specific Laboratories Two Blood Tests used when following HIV Infection CD4 Count Assists with assessment of Immune Function and Susceptibility to infection Viral Load Measures the Number of Viral Copies present in 1mL of blood Untreated infection can have millions of copies Infectivity increases as viral load rises Undetectable defined as 20 or less copies and considered non-infectious 9

Goals: Viral Load & CD4 Count CD4 Count vs Viral Load Speed Very SLOW = Viral Train Load Distance LOTS of Track = CD4 Ahead Count Graphic created in Microsoft Powerpoint by B.Pimentel 10

HIV Infection vs AIDS HIV Infection is a LABORATORY diagnosis (i.e. HIV+ or HIV-) Diagnosis of AIDS is based on both LABORATORY and CLINICAL Criteria Must have Laboratory Confirmation of HIV Infection AND CD4 Count of 200 or Less OR Presence of at least one AIDS-Defining Illness recognized by the CDC 11

Opportunistic Infections Weakened immune system unable to handle commonly-encountered agents Same list as the AIDS-Defining Illnesses used to diagnose Maintaining normal CD4 level is key to remaining healthy Most commonly diagnosed Opportunistic Infections / AIDS-Defining Illnesses Pneumocystis Carinii Pneumonia (PCP) 40% of newly diagnosed HIV Wasting Syndrome 20% of newly diagnosed Esophageal Candidiasis 10 to 15% of newly diagnosed 12

OBJECTIVE 2 Present the 6 Classes of Meds used to Treat HIV & Common Side Effects 13

CDC Guidelines released in July 2016 Anti-Retroviral Therapy (ART) Recommend starting ART in ALL HIV-infected patients REGARDLESS of labs Reduces morbidity and mortality associated with infection Reduces transmission to uninfected partners Certain populations have more urgent need for initiation of ART Pregnant Women Patients presenting with acute opportunistic infections / AIDS-defining illnesses Patients presenting with AIDS-associated malignancies Patients with CD4 Counts less than 200 Patients co-infected with Hepatitis B or Hepatitis C 14

Life Cycle of HIV Graphic from www.aidsinfo.com 15

Class 1 - Keeps HIV from Binding CCR5 Antagonist Blocks part of receptor on cell surface Prevents virus from connecting Reduces production of new virus Example Maraviroc (Trade: Selzentry) 16

Class 2 Stops Fusion to Cell Membrane Fusion Inhibitor Keeps HIV Envelope from Merging Prevents by binding to surface protein Used in Salvage Therapy Example Enfuviritide (Trade: Fuzeon) 17

Classes 3 & 4 Stop Conversion to DNA RNA DNA Non-Nucleoside or Nucleoside Reverse Transcriptase Inhibitor NNRTI or NRTI Blocks Enzyme Required for Process Must Create DNA to Replicate Examples NNRTI Two Generations NRTI 1 st Gen: Efavirenz (EFV) / Nevirapine (NVP) 2 nd Gen: Etravirine (ETR) / Rilpivirine (RPV) Lamivudine (3TC) Zidovudine (AZT or ZDV) Tenofovir Disoproxil or Alafenamide (TDF or TAF) 18

Class 5 Stop New DNA from Joining Host Integrase Strand Transfer Inhibitor INSTI Blocks Enzyme Created by HIV Allows Insertion into Host DNA Integration Allows Production of Virus Examples Dolutegravir (Trade: Tivicay) Elvitegravir (Trade: Vitekta) Raltegravir (Trade: Isentress) 19

Class 6 Keep New HIV from Maturing Protease Inhibitor (PI) Blocks Enzyme Produced by HIV Necessary to Produce Mature Virus Immature HIV Cannot Infect Cells Examples Ritonavir (Trade: Norvir) Indinavir (Trade: Crixivan) Nelfinavir (Trade: Viracept) Lopinavir/Ritonavir (Trade: Kaletra) 20

Combination Medications for HIV Allows Patient to take Fewer Pills throughout the Day and Reduces Side Effects Missed Doses can have more Serious Consequences (i.e. Resistance) Examples Truveda Tenofovir Alafenamide - Nucleoside Reverse Transcriptase Inhibitor (NRTI) Emtricitabine Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Genvoya Elvitegravir Integrase Strand Transfer Inhibitor (INSTI) Emtricitabine Nucleoside Reverse Transcriptase Inhibitor (NRTI) Tenofovir Alafenamide - Nucleoside Reverse Transcriptase Inhibitor (NRTI) Cobicistat Inhibitor of Cytochrome P450 Enzymes 21

Adjunct Medications Cobicistat Mechanism Based Inhibitor of Cytochrome P450 Enzymes Responsible for breaking down toxins and medications for excretion from body First Pass Effect is the percentage of a medication metabolized immediately after dosing Decreases Metabolism Rate in Liver and Increases Drug Levels in Blood Potentiates the Actions of ART Medications when Co-Administered Analogue of protease inhibitor Ritronavir (Norvir) with the anti-hiv activity removed 22

Adjunct Medications Sulfamethoxazole / Trimethoprim (Bactrim) Taken Daily if CD4 < 200 to prevent Pneumocystis Carinii Pneumonia (PCP) Azithromycin or Clarithromycin Taken Daily if CD4 < 50 to prevent Disseminated Mycobacterium Avium Complex (MAC) Vaccinations Pneumovax Yearly Flu Shot 23

Short-Term Side Effects of ART Usually last for several weeks and improve with time Nausea / Vomiting / Diarrhea Fatigue Headache Fever Muscle Pain Dizziness Insomnia Rash 24

Long-Term Side Effects of ART May develop over months to years and continue over time Kidney problems including kidney failure Liver damage Heart disease Insulin Resistance and/or Diabetes Hyperlipidemia Changes in how and where fat is stored in the body Osteoporosis Insomnia / Dizziness Depression / Suicidal Thoughts 25

OBJECTIVE 3 Review New Techniques for Prevention of HIV 26

Acronyms Part 2 AETC HHS HRSA RWCA AIDS Education & Training Center U.S. Department of Health & Human Services Health Resources and Services Administration Ryan White CARE Act 27

The Beginning of the Epidemic 1981: Centers for Disease Control (CDC) Publishes Report in June Presented 5 cases of pneumonia caused by a rarely-seen bacterium All patients showed signs of severe system-wide immunosuppression By December 1981, 270 cases of pneumonia nationwide & 121 of those deceased 1982: Acquired Immune Deficiency Syndrome (AIDS) initially defined by CDC Diagnosis of AIDS is based on CLINICAL presentation combined with lab work 1984: Human Immunodeficiency Virus (HIV) identified as the cause of AIDS 28

Born: 12/6/1971 Died: 4/8/1990 (18y) The Ongoing Legacy of Ryan White Hemophiliac diagnosed with AIDS in 1984 Infected with HIV after weekly blood transfusions At time of diagnosis, CD4 count was 25 Afterwards denied entry back into public school (IN) Mainly a result of community s fear and paranoia Legal battle with district reached Indiana Court of Appeals Won case, but continuing persecution by both kids & adults Nationally, became advocate about issues faced by HIV+ Died one month before his high school graduation 4m later, federally-funded program enacted for HIV+ Initially called the Ryan White CARE Act of 1990 29

Ryan White Legislation August 18, 1990 : Ryan White CARE Act (RWCA) passed CARE = Comprehensive AIDS Resources Emergency Implementation required involvement of HIV+ population at all levels Payer of Last Resort for the uninsured/underinsured 1996: RWCA Incorporates Three Established Programs into Part F Funding Dental Care for the HIV+ Population without Insurance Special Projects of National Significance (SPNS) Initiative AIDS Education and Training Centers Initiative (AETC) 30

Basic Concepts of RWCA Legislation Legislation organized into programs or Parts so funds are targeted Flexible structure allows a national program to address local needs Needs differ based on several variables Geographic areas (i.e. rural vs urban) Locations where the population has a higher rate of infection Systemic/Infrastructure needs (i.e. networking, clinic space, etc.) Funding provided for both Medical and Support services as defined by HRSA 31

Index of RWCA Parts Part A Part B Part C Part D Part F Provides funds directly to hardest hit areas Addresses prevention activities Capacity building to develop/expand access Services to women/children/infants Funds AETC/Dental Program/SPNS 32

Factors Influencing RWCA Legislation Initially, focused on providing medically-related care and support services At that time, HIV+ unable to obtain medical insurance from many carriers Providers needed resources and support to help people in the process of dying Over time, more emphasis on capacity building and increasing access to care As epidemic progresses, HIV infection is moving to a chronic disease model More and more HIV+ individuals living and will develop other chronic diseases Increasing emphasis on preventing the transmission of HIV PrEP, PEP (client-centered (prevention) TAP (population-based prevention) 33

Prevention Basics - PrEP Pre-Exposure Prophylaxis Reduces chance of infection in high-risk, HIV Negative populations Consists of daily ART dose using Truveda and effective after 7 days Effectiveness directly dependent on consistent, daily dosing 90% reduction in transmission through sexual contact and higher with condom use 70% reduction in transmission though IV drug use and needle sharing Dose is NOT sufficient if patient exposed to HIV 34

Prevention Basics - PEP Post-Exposure Prophylaxis Reduces chance of infection if potential exposure to HIV infection occurs Consists of daily ART for four to six weeks Effectiveness is directly related to the time between exposure and first dose Must be started within 72 Hours of exposure Maximum effectiveness if started within 12 to 24 of exposure 35

Prevention Basics - TAP Treatment as Prevention Public Health Initiative to maximize ART in HIV+ population Rationale Appropriate ART lowers Viral Load and reduces infectivity Important for sero-discordant couples Decreases transmission during pregnancy and childbirth 36

Some Points to Remember Over time, HIV infection has moved towards a chronic disease model HIV cannot be transmitted through tears, sweat, or saliva The key to maintaining immune function is compliance with ART Prevention of HIV transmission is becoming more emphasized over time 37

Objectives Review the basics about HIV Infection, diagnosis and management Present the 6 types of meds used to treat HIV and common side effects Review Ryan White legislation and new techniques for prevention of HIV 38

Thanks for your time!! Brent J Pimentel, MD/MPH Texas Program Manager, South Central AETC 8435 N Stemmons Fwy, Ste 1125, Dallas, TX, 75247 Work: (214) 590-3792 Fax: (214) 590-2184 Email: brent.pimentel@phhs.org I have no financial relationships or conflicts of interest. This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number U1OHA29290 for the AIDS Education and Training Centers. This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government. 39