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Natural Course of HIV Infection

Natural Course of HIV Infection. HAIVN Harvard Medical School AIDS Initiative in Vietnam. Learning Objectives. By the end of this session, participants will be able to: Explain the process that HIV infect the human cell Describe the natural progression of HIV infection

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Natural Course of HIV Infection

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  1. Natural Course of HIV Infection HAIVN Harvard Medical School AIDS Initiative in Vietnam

  2. Learning Objectives By the end of this session, participants will be able to: • Explain the process that HIV infect the human cell • Describe the natural progression of HIV infection • Explain the factors that influence the progression of HIV infection • Identify the clinical stage according to the World Health Organization (WHO)

  3. How Does HIV Infect the Human Cell?

  4. HIV Life Cycle CD4

  5. HIV Life Cycle CD4 Binding Co-receptor CCR5 và CXCR4 CD4

  6. HIV Life Cycle Fusion

  7. HIV Life Cycle HIV RNA Virion Entry

  8. HIV Life Cycle Reverse transcription HIV DNA

  9. HIV Life Cycle Translocation to nucleus

  10. HIV Life Cycle Integration

  11. HIV Life Cycle Transcription / Translation of HIV mRNA / polyprotein

  12. HIV Life Cycle Protease processing and viral assembly

  13. Vòng đời của HIV New Virus Released

  14. Protease Inhibitors (10) Fusion/Entry Inhibitors (2) Reverse Transcriptase Inhibitors (14) HIV Life Cycle & Mechanism of ARV Integration Inhibitors(1)

  15. Xét nghiệm HIV • HIV test identifies antibodies to the HIV virus in the blood • HIV test become positive after HIV infection 1-3 months • Results of two additional HIV tests should be confirmed positive before diagnosis of HIV infection

  16. Cácphươngphápxétnghiệm HIV Antibody tests • Rapid ELISA / Rapid EIA (“Rapid test”): • Results in 10 minutes to 2 hours • Positive results must be confirmed with additional testing • Western Blot (WB) • Used as a confirmatory test • Dry Blood Spot(DBS): • Used for early HIV diagnosis for infants by PCR at 4-6 weeks of age

  17. Testing in HIV patient Two common tests used to assess and monitor HIV patients are: • CD4 count • Total lymphocyte count (TLC)

  18. CD4 Count and Viral Load Testing • Plasma HIV RNA levels indicate: • the magnitude of HIV replication and • the rate of destruction of CD4+ cells • CD4 and T cell counts indicate the extent of HIV-induced immune damage already suffered

  19. Relationship Between CD4 Counts and HIV Viral Load Slow: <10,000, Fast: >100,000

  20. 1000 Asymptomatic 900 Relative level of Plasma HIV-RNA 800 CD4+ T cells 700 TB CD4+ cell Count Acute HIV infection syndrome 600 500 HZV 400 OHL 300 OC 200 PPE PCP 100 TB CMV, MAC 0 0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11 Months Years After HIV Infection Natural Progression of HIV Disease

  21. Variable Progression of HIV infection Long term non-progression CD4 500 Typical Progression OI OI 200 Rapid progression Death Death 5yrs 10yrs 15yrs

  22. Diễn biến tự nhiên của nhiễm HIV HIV progresses through various stages which include: • Primary HIV Infection • Latent Period • AIDS (advanced HIV Infection)

  23. Primary HIV Infection (1)Incidence • Occurs 2-4 weeks after acquiring HIV infection • Symptoms last 1-2 weeks • In the US and Europe, 53-93% of patients have symptoms • In Vietnam and development country, there’s no data about incidence

  24. Primary HIV Infection:Clinical Manifestations The Sanford Guide to HIV/AIDS Therapy 2005

  25. Primary HIV InfectionRash(1) • A generalized rash is a common finding: • 5-10 mm macular or papular erythematous lesions • appears 48-72 hours after fever starts • lasts for 5 – 8 days • most often involves the face and trunk • typically not pruritic • can be accompanied by oral, esophagus, anus and genital ulcerations

  26. Primary HIV Infection:Rash (2)

  27. Primary HIV Infection:Pharyngitis

  28. Latent Period: Asymptomatic HIV Disease • Characterized by gradual decline in CD4 count • Patients may be healthy for 5-10 years before symptoms develop • Symptoms can develop when CD4 < 500 cells/mm3 • OIs develop when CD4 < 200 cells/mm3

  29. Latent Period: Symptomatic HIV Infection • Generally occurs when CD4 < 500 • Conditions that may be seen when CD4 count is 200 – 500include: • Generalized lymphadenopathy • Prolonged fevers or diarrhea for > 1 month • Oral candidiasis • Pulmonary tuberculosis • Herpes zoster (Zona) • Vaginal candidiasis

  30. AIDS (Advanced HIV Infection) Final stage in the natural progression of HIV Infection Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.

  31. Manifestations of HIV Infection Vary Greatly • Some patients with CD4 > 200 can be ill with many symptoms • Some patients with low CD4 < 100 can feel healthy with no symptoms at all • All patients have decreased immune function and are at risk for OIs when: • WHO Clinical Stage 3 or 4, • CD4 < 200 • TLC < 1200

  32. What Factors Affect the Rate of Disease Progression? • Speeds disease progression: • Age • Symptoms during primary HIV • Nutritional status • Opportunistic infections (eg: TB) • High viral load • Intravenous drug use? • Slows disease progression: • OI Prophylaxis with cotrimoxazole • Antiretroviral Therapy

  33. Antiviral Therapy (ART) and HIV Progression 3 ARV % Of patients did not show AIDS or death 2 ARV 1 ARV No ARV

  34. WHO Clinical Stages

  35. Giaiđoạnlâmsàngtheo TCTYTG WHO Clinical Stage can be used to: • Estimate degree of damage done to a patient’s immune system • Follow progression of HIV disease • Determine when to start: • prophylactic treatment with cotrimoxazole • antiretroviral therapy (ART)(with or without CD4 count) WHO Clinical Stage should be evaluated at every clinic visit

  36. Stage 1: Asymptomatic • Most typical/common syndromes: • Asymptomatic • Persistent generalized lymphadenophathy • Performance Scale 1: No symtom, Normal activity

  37. Stage 2: Mildly Symptomatic • Most typical/common syndromes: • Moderate unexplained weight loss (< 10% of body weight) • Recurrent respiratory infections • Zona (Herpes zoster) • Papular pruritic eruption (PPE) • Performance Scale 2: symptomatic but normal activity

  38. Stage 3: Progressively Symptomatic • Most typical/common syndromes: • severe weight loss (> 10% of body weight) • chronic diarrhea for > 1 month • Recurrent oral candidiasis • Pulmonary tuberculosis • Performance Scale 3: symptomatic, in bed < 50% of the time

  39. Stage 4: Severely Symptomatic • Most typical/common syndromes: • Wasting syndrome due to HIV • weight loss> 10% • chronic diarrhea unexplained> 1 month • prolonged fever unexplained > 1 month • OIs • Performance Scale 4 : bedridden> 50% of the time

  40. Key Points • Primary HIV Infection phase have very high risk of infection although the test result is usually negative • On average, it takes 5-10 years from time of initial HIV infection to become ill or have symptoms • AIDS is defined as CD4 <200 or stage 4 according to WHO Clinical Stages • CD4 is the best tests to evaluate immune system status

  41. Thank you! Question?

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