Medical Exploration of HIV/AIDS: HIV Today, Fall 2016 Instructors: Dr. Lars Peters and Dr. Helene Mens Class Days: Tuesdays & Fridays Time: 14:50-16:10 Location: F24-202 Instructors

Lars Peters, M.D. (University of Copenhagen 2001). Current position: Senior Researcher, Copenhagen HIV Programme (CHIP; www.chip.dk). Primary research interest: HIV/Hepatitis coinfection. With DIS since 2007.

Helene Mens M.D., Ph.D. (University of Copenhagen 2002 and 2010). Current position: Fellow, Department of Infectious Diseases, Rigshospitalet, Copenhagen. Primary research interest: HIV evolution, natural control of HIV infection and HIV resistance. With DIS since 2010.

Course Description What does it mean to be HIV positive today? The epidemic of HIV and AIDS has changed dramatically during the last 30 years. There is no question that HIV treatment is one of the miracles of modern medicine. An AIDS-free generation has been formulated as a goal of many HIV organizations and the first person has been cured of HIV. However, in many countries around the world the mortality due to HIV infection is still high because of late diagnosis, or due to lack of access to treatment and care. The course aims at giving students an understanding of HIV and AIDS epidemic. Our goal is to provide students with evidence-based knowledge of the many aspects of the HIV pandemic covering everything from historical, biological, socio-economic and political areas. It is also our goal that students obtain a more profound knowledge of the virus, the way it causes disease, how it is detected, how it is treated, complications of treatment, local and global factors relevant to the continued spread of HIV and the many obstacles to the prevention of HIV. We will also focus on everyday aspects of living with HIV as a chronic disease by visiting HIV activists living with the disease.

Learning objectives  To provide an updated and systematic understanding of the complexity of HIV/AIDS from the infected individual to global and political perspectives  Sensitizing students to ethical, political, social, and economic issues concerning HIV/AIDS Prerequisites One year of biology and one semester of chemistry at the university level.

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Guest Lecturers Signe Worm, MD, PhD (University of Copenhagen, 2002). PhD (University of Copenhagen, 2009) Current position: Fellow, Department of Infectious Diseases, Rigshospitalet, Copenhagen. Primary research interest: HIV and cardiovascular diseases, HIV and cancer. With DIS since 2008. Álvaro Borges, MD, MSc, PhD MSc (Liverpool School of Tropical Medicine, 2011), PhD (University of Copenhagen, 2015) Current position: Postdoctoral Researcher and Clinical Lector, Department of Infectious Diseases, Rigshospitalet, Copenhagen. Primary research interest: HIV, biomarkers, inflammation, coagulation and cancer. DIS Contacts Lisbeth Borbye, Program Director Ryan Polito, Program Assistant Science & Health Programs Office, Vestergade 10-B12 Evaluation  Participation: 30%  Tests (three): 30% (10% each)  Final exam: 40% Participation covers the following areas: 1. Attendance and Level of preparation (15%) 2. Contribution to class discussions, presentations, and study questions (15%) Tests Three tests will be given during the course, one following each of the three thematic sections. The tests will only cover the information taught in that section. The tests will consist of 5-10 questions regarding the readings, guest lectures and the lectures in general, including discussion items from classes. The tests will consist of a mix of short essays and short-answer questions meaning that they should be answered by using a few precise sentences. Each test is held in class and takes 30 minutes. Final Exam The final exam is a combination of short-answer questions, case stories and essay questions. The duration of the examination is 2 hours. The format will be open-ended questions, not multiple-choice; thus, you will be asked to apply your knowledge in your own words. Final exams will be held from December 7 through December 11. The precise date and time for this exam will be announced as the time approaches. Disability resources Any student who has a need for disability accommodations must contact Sean Green to coordinate this. Upon DIS approval, students must inform the instructor of accommodations within the first two weeks of class. Office Hours The instructors have no set office hours, but you may contact them or the Program Assistant Ryan Polito Science & Health Programs Office Vestergade 10-B12) with any questions or to schedule an appointment. Attendance You are expected to attend all DIS classes when scheduled, and we will actively monitor attendance. Allowances will be made in cases of illness, but you will need to email Lars and Helene in advance. If you miss multiple classes, the Office of Academic Support will be notified and they will follow-up with you to make sure that all is well. Points will be deducted from your grade for more than one ‘unexcused’ absence. Use of Laptops or Phones in Class Use of phones in class is not allowed. Laptop use is allowed for group and project work.

Canvas Canvas is a web-based system that allows you to access course resources and communicate with your classmates and faculty. To access Canvas, you can go to the DIS homepage and click the ‘Canvas’ link on Medical Exploration of HIV/AIDS | DIS 2

the bottom of the website, or go to: https://canvas.disabroad.org/login/canvas. You can also download the Canvas App (By: Instructure) on iPhone and Android mobile smart phones. Field Studies Two field studies will take place during the semester. The Science and Health Programs Assistant will accompany you to each of the locations. Details will be given closer to the date of the field study. Dates: Wednesday October 5 13:00-17:00 Wednesday December 7 08:30-12:30 Locations:  Positivgruppen  CHIP (Copenhagen HIV Programme) at the Faculty of Health Sciences www.chip.dk Libraries These are the main libraries you will be using during your studies at DIS: 1.

DIS Library, Vestergade 10, 2nd floor (A21) http://www.disabroad.org/study-abroad-students/library/ Regular Semester hours: Monday-Friday: 09:00am-10:00pm Weekends: 11:00am-10:00pm

2.

The Danish National Library of Science and Medicine (DNLB), Nørre Alle 49, 2200 Copenhagen N. Tel.: 35 39 65 23. Opening hours: Monday through Friday 9:00 a.m.-7:00 p.m. Busses 6A, 42, 43, 184, (approx. 10 minutes from Nørreport Station). Stop Name – Fredrik Bajers Plads.

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Course Overview Lecture # 1. 2. 3. 4. 5.

6. 7. 8. 9. 10. Field Study 11.

12. 13. 14. 15.

16. 17. 18. 19. 20.

21. 22. 23. Field Study Final Exam

Date August 26

Title Presentation & The history of HIV/AIDS

August 30 HIV virology and the origin of HIV September 2 The epidemiology of HIV/AIDS September 6 Pathogenesis of HIV infection September 9 HIV vaccines Core Course Week September 12 – September 16 September 20 HIV transmission and prevention September 23 Acute HIV infection and diagnosis September 27 Test 1 September 30 Opportunistic diseases I October 4 Opportunistic diseases II October 5 Field Study, Positivgruppen October 7 Opportunistic diseases III Long Study Tour Week 1 (No Class) October 10 – October 14 October 18 HIV/hepatitis co-infection October 21 HIV and cancer October 25 Test II & Introduction to student presentations October 28 Antiretroviral therapy Long Study Tour Week 2 (No Class) October 31 – November 4 November 8 Morbidity and mortality in the cART era November 11 HIV drug resistance November 15 HIV cure & ART interruptions November 18 Adverse effects of antiretroviral therapy November 22 Mother-to-child transmission and pediatric HIV Travel Break November 23 – November 25 November 29 Student presentations December 2 Test III & HIV Treatment in Developing Countries December 6 Summary lecture + Q & A December 7 Field Study, CHIP 13:00-17:00 December 8-11 Final Exam: TBA Time: TBA Location: TBA

Teacher LP HM SW HM HM

LP LP HM SW HM

LP

LP AB LP HM

LP HM HM LP LP

HM/LP LP HM/LP

LP = Lars Peters HM=Helene Mens SW = Signe Worm AB = Alvaro Borges

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Section I – HIV Epidemiology, virology and immunology Friday, August 26 Lecture 1: Course Overview  Presentation of the course and the introduction of faculty and students  The history of HIV/AIDS Lecturer: Lars Peters Reading assignment: “The History of HIV/AIDS”. In compendium Tuesday, August 30 **Elect Class Representatives** Lecture 2: HIV Virology and the origin of HIV  The structure of HIV  HIV replication & evolution  The origin of HIV Lecturer: Helene Mens Reading assignment: “Virology” uploaded to Canvas Friday, September 2 Lecture 3: The epidemiology of HIV/AIDS  The global incidence and prevalence of HIV/AIDS  Regional differences Lecturer: Signe Worm Reading assignment: Hankins, Curr HIV/AIDS Rep 2013, “Overview of the Current State of the Epidemic” In compendium + UNAIDS 2015 “AIDS by the Numbers” uploaded to Canvas Tuesday, September 6 Lecture 4: Pathogenesis of HIV infection  HIV and the immune system Lecturer: Helene Mens Reading assignment: “HIV Pathogenesis” uploaded to Canvas. Marchetti et al "Microbial Translocation in the Pathogenesis of HIV Infection and AIDS" In compendium

Friday, September 9 Lecture 5: HIV vaccines Lecturer: Reading assignment:

Helene Mens HIV Vaccine. Uploaded to Canvas + Rerks-Ngarm et al, NEJM 2009, “Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand” + Johnston & Fauci, NEJM 2011, “HIV Vaccine Development— Improving on Natural Immunity”. In compendium

September 12 – September 16 Core Course Week No elective class

Tuesday, September 20 Lecture 6: HIV transmission and prevention  Routes of transmission  Persons at risk  Male circumcision and risk of transmission  Pre-exposure Prophylaxis (PrEP) Lecturer: Lars Peters Reading assignment: “HIV transmission & strategies to prevent transmission of HIV”. In compendium

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Friday, September 23 Lecture 7: Acute HIV infection. Diagnosis and management of HIV patients  Signs and symptoms of acute HIV infection  Diagnosis of HIV infection  Management of the HIV-infected patient Lecturer: Lars Peters Reading assignment: To be uploaded to Canvas

Tuesday, September 27 Lecture 8: Test I & Film  30 minute test covering Section I Lecturer: Helene Mens Reading assignment: None Section II – HIV related morbidity & mortality Friday, September 30 Lecture 9: Opportunistic Diseases I  Introduction to opportunistic diseases  Signs & symptoms of common AIDS Diseases Lecturer: Signe Worm Reading assignment: Libman & Makadon, HIV, p 163-204

Tuesday, October 4 Lecture 10: Opportunistic Diseases II  Signs & symptoms of common AIDS Diseases  Case Lecturer: Helene Mens Reading assignment: “CNS disease in HIV infection”, uploaded to Canvas

Wednesday, October 5 Field Study Time: 13:00-17:00 Location: Positivgruppen **More details will be posted to Canvas closer to date of field study**

Friday, October 7 Lecture 11: Opportunistic Diseases III  Signs & symptoms of common AIDS Diseases  Case Lecturer: Lars Peters Reading assignment: “HIV-related pulmonary infections” Uploaded to Canvas October 10 – October 14 Long Study Tour / Break Tuesday, October 18 Lecture 12: HIV/Hepatitis Co-infection  Hepatitis B & C  HIV and hepatitis B/C co-infection  Case Lecturer: Lars Peters Reading assignment: “Hepatitis B & C and HIV/viral hepatitis co-infection”. In Compendium Medical Exploration of HIV/AIDS | DIS 6

Friday, October 21 Lecture 13: HIV and Cancer  AIDS defining cancers  Non-AIDS cancers in HIV patients  Case Lecturer: Alvaro Borges Reading assignment: Borges. Curr Opin HIV AIDS 2013: “Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk”. In compendium Tuesday, October 25 Lecture 14: Test II & Introduction to student presentations  30 minute test covering Section II Lecturer: Lars Peters Reading assignment: None

Section III – HIV treatment Friday, October 28 Lecture 15: Antiretroviral Therapy  Antiretroviral treatment history  Criteria for initiation of antiretroviral treatment Lecturer: Helene Mens Reading assignment: European AIDS Clinical Society 2015 Guidelines, page 4-11. In compendium October 31 – November 4 Break

Tuesday, November 8 Lecture 16: Morbidity and mortality in the cART era Lecturer: Lars Peters Reading assignment: “Morbidity and mortality in the cART era” in compendium

Friday, November 11 Lecture 17: HIV drug resistance  Resistance development  Overcoming resistance Lecturer: Helene Mens Reading assignment: “HIV Drug Resistance” to be uploaded to Canvas

Tuesday, November 15 Lecture 18: Adverse effects of antiretroviral therapy  Short- and long term toxicities  Case Lecturer: Lars Peters Reading assignment: To be uploaded to Canvas

Friday, November 18 Lecture 19: HIV Cure & ART interruptions Lecturer: Helene Mens Reading assignment: Chun et al "HIV reservoirs as obstacles and opportunities for an HIV cure", “Treatment interruption strategies – how great are the risks?” In compendium Medical Exploration of HIV/AIDS | DIS 7

Tuesday, November 22 Lecture 20: Mother-to-child transmission of HIV & Pediatric HIV  Risk factors for MTCT  Strategies for prevention of MTCT  Pediatric HIV  Case Lecturer: Lars Peters Reading assignment: Luzuriaga & Mofenson. N Engl J Med 2016, “Challenges in the Elimination of Pediatric HIV-1 Infection” in Compendium November 23 – November 25 Long Study Tour / Break

Tuesday, November 29 Lecture 21: Student presentations Lecturer: Helene Mens/Lars Peters Reading assignment: None

Friday, December 2 Lecture 22: Test III & HIV Treatment in Developing Countries  30 minute test covering Section III  ART in developing countries Lecturer: Lars Peters Reading assignment: None

Tuesday, December 6 Lecture 23: Summary, evaluation and Q & A  Evaluation of the course  Q & A session Lecturers: Helene Mens/Lars Peters Reading assignment: None

Wednesday, December 7 Field Study Time: 08:30-12:30 Location: CHIP, Rigshospitalet, University of Copenhagen **More details will be posted to Canvas closer to date of field study** Final Exam Location/Time: December 8-11 DIS, TBA

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Reference list Textbooks 1. I. Edward Alcamo, AIDS the Biological Basis, 5th edition 2.

Libman and Makadon, HIV, 3rd edition

Articles in Compendium/Binder 1. Peters, Lars: History of HIV/AIDS 2. Sharp, Paul M.; Hahn, Beatrice H.: The Evolution of HIV-1 and the Origin of AIDS 3. Silvestri, Guido; Marchetti, Giulia; Tincati, Camilla: Microbial Translocation in the Pathogenesis of HIV Infection and AIDS 4. Peters, Lars: HIV transmission & strategies to prevent transmission of HIV 5. Cohen, Myron S.; Haynes, Barton F; George, Shaw; McMichael, Andrew J: Acute HIV-1 Infection 6. Pitisuttihum, Punnee; Rerks-Ngarm, Supachai; et al.: Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand 7. Fauci, Anthony S.; Johnston, Margaret I.: HIV Vaccine Development - Improving on Natural Immunity 8. Cohen, Myron S.; Smith, M Kumi; et al.: Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here? 9. Dubrow, Robert; Borges, Álvaro H; Silverberg, Michael J: Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk 10. Mitsuyasu, Ronald T.: Non-Aids-Defining Cancers 11. Peters, Lars: Hepatitis B & C and HIV / viral hepatitis co-infection 12. European AIDS Clinical Society: European AIDS Clinical Society Guidelines 13. Peters, Lars: Morbidity and Mortality in the cART era 14. Lewin, Sharon R; Deeks, Steven G; Havlir, Diane V: The end of AIDS: HIV infection as a chronic disease 15. Poole, Charles; et al.; Shiels, Meredith S.: A Meta-Analysis of the Incidence of Non-AIDS Cancers in HIV-Infected Individuals 16. Fauci, Anthony S.; Moir, Susan; Chun, Tae-Wook: HIV reservoirs as obstacles and opportunities for a HIV cure 17. Gras, Luuk; et al.; Kesselring, Anouk: Immunodeficiency as a Risk Factor for Non-AIDS 18. Paton, Nicholas I.: Treatment interruption strategies: how great are the risks? 19. Mofenson, Lynne M; Luzuriaga, Katherine: Challenges in the Elimination of Pediatric HIV-1 Infection Additional articles may be handed out or posted on Canvas prior to the relating session. WEB SITES NIH: http://aidsinfo.nih.gov/ [Information on HIV/AIDS treatment, prevention and research. Guidelines.] WHO: http://www.who.int/topics/hiv_infections/en/ [Guidelines, reports and global epidemiology] UNAIDS: http://www.unaids.org/en/ [Source of annual ”AIDS epidemic update”, epidemiology] CDC: http://www.cdc.gov/hiv/ [Guidelines, reports, epidemiology, fact sheets] Medical Exploration of HIV/AIDS | DIS 9

The International AIDS Society-USA: http://www.iasusa.org/ [Cases, drug resistance data and more] Infectious Disease Society of America: http://www.idsociety.org/ [Guidelines on prevention and treatment of opportunistic infections] Medscape: http://www.medscape.com/hiv-home?src=pdown [Cases, educational material and more] Global fund to fight against AIDS, tuberculosis and malaria: http://www.theglobalfund.org/en/ Bill and Melinda Gates Foundation: http://www.gatesfoundation.org/GlobalHealth/ Clinical Care Options: http://clinicaloptions.com/HIV.aspx Hepatitis resources: www.hivandhepatitis.com The Clinton Foundation: http://www.clintonfoundation.org/ HIV Database: http://www.hiv.lanl.gov/content/index [Contains data on HIV genetic sequences, immunological epitopes, drug resistance-associated mutations, and vaccine trials. The website also gives access to a large number of tools that can be used to analyze these data.]

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