HIV Update Discuss News Items Regarding Cures And Patent Issues With PrEP.

4/26/2019 Objectives HIV Update Discuss changes in the diagnosis, treatment, and monitoring of HIV/AIDS throughout the years Describe the use of pre-exposure prophylaxis (PrEP) in at-risk populations. Discuss news items regarding “cures” and patent issues with PrEP. Mitzi Glover, PhD, MT(ASCP) HIV/AIDS HIV - human immunodeficiency virus AIDS - acquired immunodeficiency syndrome, the most advanced stage of HIV infection. HIV attacks and destroys the infection-fighting CD4 cells of the immune system. Loss of CD4 cells diminishes the patient’s ability to fight infections and certain cancers. Without treatment, HIV gradually destroys the immune system and advances to AIDS. HIV treatment HIV transmission Spread through contact with the blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, or breast milk In the US, spread mainly by sexual contact or sharing needles Stages of HIV infection Antiretroviral therapy (ART) utilizes a combination of HIV medicines taken every day. ART not a cure- helps people with HIV live longer, healthier lives. HIV medicines can also reduce the risk of transmission 1

4/26/2019 Stages of HIV infection Stages of HIV infection Acute HIV Infection Generally develops within 2 to 4 weeks after infection Patients commonly exhibit flu-like symptoms, such as fever, headache, and rash. HIV multiplies rapidly, and the very high level of HIV in the blood greatly increases the risk of HIV transmission. Chronic HIV Infection Also referred to as asymptomatic HIV infection or clinical latency HIV continues to multiply in the body but at very low levels. Patients may not display any symptoms HIV transmission is possible at any stage of HIV infection—even if a person with HIV has no symptoms of HIV. Without treatment, chronic infection generally progresses to AIDS in 10 years or so, but this is variable. Stages of HIV infection AIDS Final, most severe stage Due to damage to the immune system, the body can’t fight off opportunistic infections. Diagnosis of AIDS - CD4 count of less than 200 cells/mm3 or if they have certain opportunistic infections. Without treatment, AIDS patients typically only survive about 3 years today Deaths due to complication from opportunistic infections and cancers Types of HIV HIV-1 Discovered first Most prevalent worldwide More infectious Progresses more rapidly HIV-2 55% genetically different Most common in western Africa Less infectious Progresses more slowly Testing today can diagnose either. Groups or sub-groups of HIV-1 M - ‘major’ group, responsible for majority of the global HIV epidemic. N, O and P - much less common. O - 5% of infections in several west and central African countries N and P -rarely identified (in Cameroon). All groups can be detected by HIV-1 antibody tests. Subtypes of Group M At least 9 genetically different subtypes in Group M Also, subtypes can combine genetic material to form hybrids circulating recombinant forms (CRFs) Approximately 89 known CRFs in existence 2

4/26/2019 Subtype distribution Dominant subtype in the Americas and Western Europe is B. Therefore, most research conducted in subtype B populations. Less research on subtype C, although nearly 50% of all people living with HIV have subtype C (very common in high prevalence countries of Southern Africa and India). Rates of HIV diagnoses - 2017 Find your region 3

4/26/2019 AIDS diagnosis Diagnosis of AIDS is based on the following criteria: A drop in CD4 count to less than 200 cells/mm3 (500-1600). A CD4 count measures the number of CD4 cells in a sample of blood. OR The presence of certain opportunistic infections. Although an AIDS diagnosis indicates severe damage to the immune system, HIV medicines can still help people at this stage of HIV infection. With medical treatment, progression to AIDS is less frequent today, but this was not always the case. 1980s- USA 1981- cases of rare diseases among gay men in New York and California Kaposi's Sarcoma (a rare cancer) Pneumocystis carinii pneumonia (PCP) Unclear why these cancers and opportunistic infections were spreading in the gay community. Pneumocystis (carinii) jiroveci pneumonia Opportunistic fungal infection Previously classified as a parasite Symptoms- shortness of breath, nonproductive cough, fever Most common pneumonia in AIDS patients (particularly if CD4 count 200 cells/uL) Kaposi sarcoma Kaposi sarcoma- cancer caused by human herpes virus-8 (HHV-8) Opportunistic; damage to the immune system by HIV allows cells with HHV-8 to multiply Manifests as lesions on the body 1980s (cont) CDC uses term AIDS (Acquired Immune Deficiency Syndrome) for the first time CDC issues Precautions for Clinical and Laboratory Staffs AIDS suspected in newborns of women who were IV drug users and/or worked in the sex trade Hemophiliacs develop AIDS Transfusions linked to AIDS 4

4/26/2019 1981 By the end of the year, 337 reported cases of severe immunodeficiency in U.S. 130 of these were already dead v-and-aids-timeline HIV life cycle 1. Binding to CD4 cell 2. Fusion of HIV envelope with cell membrane, allowing entry into cell 3. Reverse transcription to convert the viral RNA to DNA 4. Integration of the viral DNA into host DNA 5. Replication using host machinery to make HIV proteins 6. Assembly of new viruses 7. Budding out of the cell 1985– An Early Frost (NBC) First major film about AIDS in U.S. Nervous sponsors pulled their advertising. 1984 French and American research teams discover the retrovirus that causes AIDS French name it Lymphadenopathyassociated virus (LAV) Americans name it Human T cell lymphotrophic virus type III (HTLV-III) 1986 Human immunodeficiency virus (HIV) 1985- Fears spread Ryan White 13 year old hemophiliac who contracted HIV in blood products Barred from attending classes at his school in Indiana Rock Hudson First celebrity to go public with a diagnosis of AIDS Died of AIDS-related illness in 1985 Bequeaths money to help set up American Foundation for AIDS Research (amfAR) 5

4/26/2019 1985- First commercial blood test approved ELISA, detected IgG antibodies Blood banks began screening blood supply Window period of infectivity detection was 56 days HIV positive in the 1980s Essentially a death sentence as antigen 1987- AIDS Memorial Quilt Conceived by gay rights activist Cleve Jones Memorial to loved ones lost to AIDS Initially, displayed in October 1987 with 1920 panels Today, 48,000 panels ( 50 miles long). Can no longer be displayed at any one location 1987 Use of western blot for confirmation of HIV diagnosis begins Immunofluorescence assay also used, but not as popular v-and-aids-timeline 1987- FDA approves first HIV drug Zidovudine (AZT) Nucleoside reverse transcriptase inhibitor (NRTI) We will talk about drugs again later. Western blot- confirmatory testing Viral proteins from a lysate separated by gel electrophoresis Transferred to nitrocellulose paper and incubated with patient serum Patient antibodies to the viral proteins will bind and can be detected by binding to antihuman IgG 6

4/26/2019 Late 1980s 2nd and 3rd generation ELISAs introduced 1988 The brochure "Understanding AIDS" is sent to every household in the US—107 million copies in all. Window period of infectivity detection shortened to 42 days (2nd gen) and then 22 days (3rd gen) 7

4/26/2019 1989 CDC releases Guidelines for Prevention and Transmission of HIV and Hepatitis B to HealthCare and Public-Safety workers. Universal precautions is an approach to infection control to treat all human blood and body fluids as if they were known to be infectious for HIV, HBV and other bloodborne pathogens What is wrong with this picture? 8

4/26/2019 Amanda Blake Died 1989, AIDS-related complications Believed to have been infected by former husband Ryan White CARE (Comprehensive AIDS Resources Emergency) Actenacted in 1990 To improve quality and availability of care for medically underserved individuals and families affected by HIV/AIDS. Health Resources and Services Administration (HRSA) allocates funding to programs created by the CARE Act. 1990 1990 CDC reports a possible case of a Florida dentist infecting patient with HIV In the end, a total of 6 patients believed to be infected by the dentist Dentist passed away in 1990 1991- CDC issues recommendations for healthcare workers with HIV Was this a case of improper sterilization? Ryan White passed away just months before enacted. Could it have been intentional? 1991 Earvin “Magic” Johnson suddenly retires from basketball, announcing that he is HIV-positive At the time, many Americans viewed AIDS as a gay white man’s disease. Johnson, a heterosexual, was one of the first sports stars to go public about his HIV-positive status. Became a prominent spokesperson for AIDS awareness -11-9202220020-story.html 9

4/26/2019 1991 1992 Freddie Mercury, lead singer/songwriter of the band Queen, dies from bronchial pneumonia, a complication of AIDS. CDC reports HIV infection became the number one cause of death among men aged 25-44 years in 1992 1991– Angels in America Anthony Perkins Screenplay written by Tony Kushner (born in NYC, but moved to Lake Charles, LA, when he was 2) Pulitzer prize winning and Tony award-winning play Adapted into an Emmy award-winning HBO miniseries in 2003 Died in 1992 from complications of AIDS-related pneumonia Robert Reed (aka Mike Brady) 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS (CDC) Died of colon cancer in 1992 Had never revealed publicly that he was gay or had AIDS After his death, the National Enquirer put his death certificate on front page, to demonstrate that HIV contributed to his death. Prior to this, AIDS definition called for positive HIV antibody test, and certain opportunistic infections 1993 revision expands definition to include any HIV with 200 CD4 T cells/uL, or a CD4 T cell % of total lymphocytes of less than 14. - Expansion retains the 23 clinical conditions in the AIDS definition with the addition of three clinical conditions: pulmonary tuberculosis recurrent pneumonia invasive cervical cancer To be used by all states for AIDS case reporting effective January 1, 1993. 10

4/26/2019 1993-- Philadelphia Arthur Ashe Contracted HIV from blood transfusion Died from AIDS related pneumonia in 1993 Greg Louganis Olympic diver Came out as HIV in 1995 Won medals in 3 different Olympics, but, “Never got a Wheaties box.” 1994 First oral fluid collection device to be used in conjunction with laboratory testing for HIV approved 1996 First home (sort of) and urine tests approved 11

4/26/2019 1996 1996 FDA approves HIV viral load test- Nucleic acid test (NAT),also called nucleic acid amplification test (NAAT), HIV viral RNA FDA approves HIV viral load test- Nucleic acid test (NAT),also called nucleic acid amplification test (NAAT), HIV viral RNA Detects the presence of viral infection by directly testing for viral nucleic acids and can be used to screen whole blood and plasma samples. Expensive 1996 1996 Calypte (Seradyn) HIV-1 Urine EIA approved Highly active antiretroviral therapy (HAART) introduced. Combination of drugs from different classes - must be taken daily Produced with developing countries in mind Not waived HIV-1 antibodies detected Different classes of drugsdifferent targets HIV drugs work by blocking HIV at different stages of the HIV life cycle. 12

4/26/2019 https://aidsinfo.nih.gov ct-sheets/19/73/the-hiv-life-cycle Binding Binding HIV binds to molecules on the surface of the CD4 cell First binds CD4 receptor, then either a CCR5 or CXCR4 coreceptor.” ossary/4597/binding Fusion ossary/4597/binding Fusion HIV viral envelope fuses with the CD4 cell membrane. Fusion allows HIV to enter the CD4 cell. Once inside the cell, the virus releases its RNA and enzymes. ossary/3320/fusion ossary/3320/fusion 13