0% 0% 0% Parasite. 2. RNA-virus. RNA-virus
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1 HIV/AIDS and Treatment Manado, Indonesia 16 november HIV [e] EDUCATION
2 HIV is a 1. DNA-virus 2. RNA-virus 3. Parasite 0% 0% 0% DNA-virus RNA-virus Parasite
3 HIV HIV is a RNA-virus. HIV is an RNA virus which uses DNA for its replication. A virus is unable to replicate (reproduce) on its own and must first infect a living cell in order to replicate.
4 HIV has to infect living cells in order to replicate What kind of cells? 1. Erythrocytes 2. Lymphocytes 3. Thrombocytes 0% 0% 0% Erythrocytes Lymphocytes Thrombocytes
5 The lifecycle of HIV-1
6 Cellular CD4 receptor Human DNA chromosome CD4 ( T Helper) Cell
7 Reverse transcriptase Cellular CD4 receptor gp41 HIV HIV RNA chromosome Human DNA chromosome CD4 ( T Helper) Cell
8 1. HIV approaches CD4 cell 4. Fusion of cell and virus 2. HIV-CD4 interaction 3. Connection gp41
9 Cellular CD4 receptor HIV RNA chromosome Human DNA chromosome CD4 ( T Helper) Cell
10 Cellular CD4 receptor RNA nucleotides HIV RNA chromosome Human DNA chromosome CD4 ( T Helper) Cell
11 Reverse transcriptase Cellular CD4 receptor RNA nucleotides DNA nucleotides HIV RNA chromosome Human DNA chromosome CD4 ( T Helper) Cell
12 Reverse transcriptase Cellular CD4 receptor HIV RNA chromosome HIV DNA provirus Human DNA chromosome CD4 ( T Helper) Cell
13 Integrase Cellular CD4 receptor Reverse transcriptase HIV RNA chromosome HIV DNA provirus Human DNA chromosome CD4 ( T Helper) Cell
14 Reverse transcriptase Cellular CD4 receptor HIV RNA chromosome HIV DNA provirus Human DNA chromosome CD4 ( T Helper) Cell
15 Cellular CD4 receptor HIV HIV RNA chromosome HIV DNA provirus Human DNA chromosome CD4 ( T Helper) Cell
16 Acute HIV-infection
17 From HIV- exposure at mucosal surface to spreading to organs. How long does it take? minutes 2. 1 day days 4. Three months 0% 0% 0% 0% 10 minutes 1 day 11 days Three months
18 Day 0 Day 0-2 Exposure to HIV at mucosal surface (sex) Virus collected by dendritic cells, carried to lymph node Day 3-11 HIV replicates in CD4 cells, released into blood Day 11 on Kahn JO, Walker BD. N Engl J Med. 1998;339: Virus spreads to other organs
19 29 year old man, no medical history 2 weeks of malaise, myalgia and since a couple days a rash Four weeks ago unprotected sex Complaints of severe fatigue, no weight loss or mouth sores 1week ago his GP gave him antibiotics with no effect Physical exam: temperature of 38.3 C, diffuse adenopathy, maculopapular rash
20 Rash
21 Test results HIV RNA: copies/ml HIV antibody: negative What is your diagnosis? Acute HIV-infection
22 Primary HIV Infection: Signs & Symptoms 80-90% of patients will be symptomatic A mononucleosis-like like illness of non-specific signs and symptoms Signs and symptoms typically begin 1-4 weeks post-exposure Kahn JO, Walker BD. N Engl J Med. 1998;339: Schacker T, et al. Ann Intern Med. 1996;125:
23 Primary HIV Infection: Common Signs & Symptoms fever 86 lethargy 74 myalgias rash headache pharyngitis N = 160 patients with PHI in Geneva, Seattle, and Sydney adenopathy % of patients Vanhems P et al. AIDS 2000; 14:
24 Typical Risk of Unprotected Exposures Estimated Average Per Contact Transmission Risk (%) Shared Needles 0.7% Occupational Needlestick 0.3 % Male to female, vaginal sex 0.2% Female to male, vaginal sex 0.1% Receptive oral sex with male 0.03%
25 How long is your diagnostic window? The current HIV-antibody screening tests are able to recognise almost 99.5 % of HIV infections A. 2 weeks B. 1 month C. 3 months D. 1 year.after primary HIV infection 0% 0% 0% 0% 2 weeks 1 month 3 months 1 year 90
26 How long is your diagnostic window? The current HIV-antibody screening tests are able to recognise almost 99.5% of HIV-infections A. 2 weeks B. 1 month C. 3 months D. 1 year..after primary infection with HIV
27 Typical Course of Primary HIV HIV RNA 1 mil 100,000 10,000 1, Exposure HIV RNA Symptoms Ab + _ HIV-1 Antibodies Days
28 HIV-markers and disease progression
29 HIV Disease Progression Progression can be monitored by: Clinical markers: HIV/AIDS-related conditions Laboratory markers Increase in blood virus load Decrease in CD4 cell count
30 CD4 Count, Viral Load, and Clinical Course Primary Infection Seroconversion Plasma HIV RNA Plasma RNA Copies CD4 Cells Intermediate Stage AIDS CD4 Cell Count 1, Weeks Up to 12 Years 2-3 Years
31 HIV Infection is characterized by a steady decline in the number of CD4 cells Acute Infection CD4 Cell Count (cells/mm³) 1, Asymptomatic HIV Infection AIDS CD4 cell count high risk of opportunistic infections 4-8 Weeks Up to 12 Years 2-3 Years Time
32 Association between opportunistic infections and CD4 + -lymphocyte count CD4 + -lymphocyte count (cells/µl) Herpes Zoster Tuberculosis Oral candidiasis time Pneumocystis carinii pneumonia Esophageal candidiasis Toxoplasmosis, cryptococcosis Mycobacterium avium complex Cryptosporidiosis, PML
33 Antiretroviral therapy
34 What is antiretroviral therapy? ART Antiretroviral Therapy ARV Antiretroviral cart combination Antiretroviral Therapy HAART Highly Active Antiretroviral Therapy
35 What kind of classes do we have? NRTI s NNRTI s PI s (Entry inhibitors) (Fusion inhibitors) (Integrase inhibitors)
36 Available FDA approved drugs Classes NRTIs NNRTI Protease inhibitors AZT DDI DDC D4T 3TC ABC AZT/3-TC ZT/3TC/ABC TDF FTC 3TC/ABC TDF/FTC NVP Etravirine EFV Fusion inhibitors Enfuvirtide CCR5 antagonist Maraviroc Integrase inhibitor Raltegravir Saquinavir Darunavir Indinavir Nelfinavir Amprenavir Lopinavir/rtv Atazanavir Fosamprenavi Tipranavir
37
38
39
40 PI NRTI NRTI + or (the NRTI backbone ) NNRTI
41 Combination of at least 3 drugs, usually: 2 NRTIs (the NRTI backbone ), plus: 1 NNRTI or 1-2 PIs Therapy with only one or two agents allows HIV to overcome therapy through resistance mutations
42 Goals of HAART Prolong life and improve quality of life Achieve maximal suppression of HIV Low (undetectable) viral load Reverse immune system damage Increase CD 4 -count
43 Initiation of Antiretroviral Therapy: Key Considerations Symptoms & Opportunistic Infections CD4 count Anticipated Adherence - patient readiness
44 CDC A: Asymtomatic Lymphaden. B: Symptomatic C: AIDS defining illness 1 >500 CD4 Deferal treatment start treatment Start treatment CD start treatment Start treatment Start treatment 3 <200 CD4 Start treatment Start treatment Start treatment
45 When to start? DHHS Guidelines 2008 update january
46 Male 28 years, HIV+ CD4 cell count: 150/µl, retrosternal pain 1. Yes 2. No Start HAART? 0% 0% Yes No 90
47 Male 28 years, HIV+ CD4 cell count: 370/µl, retrosternal pain Start HAART? 1. Yes 2. No 0% 0% Yes No 90
48 Male 42 years, HIV+, dry cough since three weeks, breathing frequency 40/min CD4 cell count: 170/µl X-thorax: Start HAART? 1. Yes 2. No 0% 0% Yes No 90
49 Male 42 years, HIV+, dry cough since three weeks, breathing frequency 40/min CD4 cell count: 220/µl X-thorax: Start HAART? 1. Yes 2. No 0% 0% Yes No 90
50 Male 42 years, HIV+, dry cough since three weeks, breathing frequency 40/min, CD4 cell count: 170/µl X-thorax: When to start HAART? 1. Now Weeks 3. 3 months 0% 0% 0% Now 2-8 Weeks 3 months 90
51 Woman 34 years old; HIV+, Unexplained weight loss; 66 kg 46 kg, CD4 cell count: 410/µl Start HAART? 1. Yes 2. No 0% 0% Yes No 90
52 The treatment of patients with symptomatic conditions (CDC B) or an AIDS defining illness (CDC C) should not depend on a CD4 cell count!
53 Pfffffffff finished!
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