Acute HIV Infection. Acute

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1 Acute HIV In nfection n Acute HIV Infection Jintanat t Ananworanich, MD, PhD Investigator, AFRIMS (Armed Forces Research Institute of Medical Sciences) Chief of SEARCH Deputy Director in Scientific Affairs, HIV-NAT, The Thai Red Cross AIDS Research Centre Jintanat.a@searchthailand.org ; Jintanat.a@hivnat.org

2 Outline Acute HIV In nfection n Immunopathogenesis Clinical manifestation Diagnosis Consideration for treatment RV254 Establish a cohort of acute HIV infected subjects in Thailand

3 Acute HIV In nfection nwhy is acute HIV infection important? Understand early immunologic and virologic Design effective events preventive HIV vaccine Early treatment to preserve T cells and limit reservoir Achieve functional cure = Drug free remission Diagnose HIV at its height ht of transmission potential Limit HIV spread

4 Immunopathogenesis of Acute HIV Infection Acute HIV Infectionn

5 Brenchley JM, et al. 2004:200 (6):P749-59

6 Innate and adaptive immunity after HIV transmission McMichael AJ, Nature Review 2010

7 Window of Opportunity Usually mediated by a single virion McMichael AJ, Nature Review 2010

8 Diagnosis of Acute HIV Infection Acute HIV Infectionn

9 Acute HIV In nfection n Fiebig Laboratory Staging gof Acute HIV Infection Cohen MS, J Infect Dis 2010

10 Acute HIV In nfection ndiagnosis of Acute HIV Infection Fiebig I/II Fiebig III/IV HIV EIA (4 th generation EIA) Negative Positive Nucleic acid testing 2 nd generation EIA Negative Positive Negative Positive No HIV infection Acute HIV infection Chronic HIV infection Procedures in RV254

11 Acute HIV In nfection n Clinical Manifestation of Acute HIV Infection

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13 Consideration for Treatment Acute HIV Infectionn

14 Acute HIV In nfection nconsideration for Treatment Pros Cons Preservation of immune Toxicity functions Drug resistance Improve surrogate markers of HIV disease Quality of life Limit transmission Unknowns Will it alter clinical i l disease? Is this a life long treatment? Can patient interrupt treatment? Bell SK, J Infect Dis 2010

15 Summary Acute HIV In nfection n The first 3 weeks of infection offers a window of opportunity to contain HIV through novel interventions CD4+ T cell depletion particularly in the gut occurs very early in HIV infection The majority of HIV infected persons display symptoms of acute retroviral syndrome (fever, rash, sore throat) which is usually misdiagnosed Antiretroviral treatment is optional. Although it may limit immunedestructionand viral reservoir, there is currently no clear clinical benefit to early treatment Knowledge of acute HIV infection is crucial to the design of effective prevention and treatment. Subjects should be encouraged to enroll in clinical trials y

16 15 October 2010

17 RV254 Acknowledgement Acute HIV In nfection n AFRIMS Alexandra Schuetz Mark desouza Rapee Trichavaroj Vatcharain Assawadarachai Yuwadee Phuangngern Wiriya Rutvisuttinunt Nantana Tantibul WRAIR Jerome Kim Nelson Michael Mary Marovich Jeff Currier Sodsai Tovanabutra Merlin Robb Silvia Kim Thai Red Cross/SEARCH/HIV NAT/Chula Praphan Phanuphak Nipat Teeratakulpisarn Rungsun Rerknimitr Nittaya Phanuphak Thep Chalermchai h Duanghathai Suttichom Nitiya Chomchey Thai US CDC collaboration Somprartthana Rtt Rattanamanee Panadda Sawangsinth Bessara Nuntapinit Frits van Griensven Pairoa Praihirunkit Siriwat Akapirat Supaporn Chaikummao James Fletcher Wanwarang Khobchit Wipas Wimonsate Sasiwimol i lubolyam Sakuna Suksawad NIAID Sukalya Lerdlum Irini Sereti Ajchariyarat Sangdara Mantana pothisri Jacob bet Estes Kultida Poltavee Wiriyaporn ii Ridtitid i Jessica Hodge Hathairat Savadsuk Umaporn Siangphoe Michael Yao Suwittra Chaemchuen Huntington Memorial Adam Rupert Napaporn Sailasuta Joseph Chiu Frank Maldarelli Robert Paris Industry Robin Dewar Viseth Ngauy Gilead (TDF, FTC) UCSF VGTI Rafick Sekaly Merck (EEV, RAL) Victor Valcour Nicolas Chomont Pfizer (MVC) Claire Vandergeeten Monogram (Trofile)