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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 should be able to: Describe the natural progression of HIV infection Explain the factors that influence the 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 should be able to: • Describe the natural progression of HIV infection • Explain the factors that influence the progression of HIV infection

  3. Basic Concepts of HIV Virology

  4. Overview of Virology • Viruses are classified as either DNA or RNA viruses • The building blocks of viral genes are nucleotides • RNA and DNA are made of nucleotides, which code for the production of proteins • These proteins are the components of the virus (envelope, antigens, enzymes etc)

  5. Overview of HIV Virology • HIV is an RNA virus consisting of 9200 nucleotides • HIV is a “retrovirus”, meaning: • replication occurs from RNA to DNA using the enzyme Reverse Transcriptase • DNA created is then integrated into the host cell genome (T lymphocyte) • further HIV virus (RNA and proteins) are then produced using this DNA complex

  6. HIV Structure

  7. Definitions (1): CD4 Cell • CD4 cell is one type of T-Lymphocyte • HIV binds with receptors on the CD4 cell to enter and infect the cell • After infection, the number of CD4 cells gradually declines over time • The number of CD4 cells in the body, or the CD4 cell count, indicates extent of HIV-induced immune damage

  8. Definitions (2): Viral Load • The viral load is the amount of HIV in the blood • The level of HIV in the blood indicates the magnitude of HIV replication and rate of destruction of CD4 cells • The viral load test measures the amount of HIV RNA in the plasma

  9. Definitions (3): HIV Testing • HIV antibody test identifies antibodies to the HIV virus in the blood • It takes 1-3 months following HIV infection for the antibodies to be detected on a standard HIV antibody test

  10. How Does HIV Infect the Human Cell?

  11. 5 1 6 4 2 Reverse tran-scriptase HIV RNA 7 3

  12. 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

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

  14. Natural Progression of HIV Infection HIV progresses through various stages which include: • Primary HIV Infection • Latent Period • Symptomatic HIV Infection • AIDS (advanced HIV Infection)

  15. Primary HIV Infection (1) • Occurs 2-4 weeks after acquiring HIV infection • Symptoms last 1-2 weeks and most commonly include: • Fever • Myalgia/arthralgia • Pharyngitis • Adenopathy • Rash

  16. Primary HIV Infection (2) • Seroconversion usually occurs within 4 –12 weeks, so HIV antibody tests are usually NEGATIVE in this period • If primary HIV infection is suspected and HIV test is negative, repeat test after 1 and 3 months • HIV Viral Load testing can diagnose acute HIV infection

  17. Primary HIV Infection (3) • 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

  18. Rash Associated with Primary HIV Infection (1)

  19. Rash Associated with Primary HIV Infection (2)

  20. Primary HIV Infection: Treatment • Treatment is supportive • Treat fever with paracetamol • Treat pain with NSAIDS or opiates • Maintain adequate hydration • Counsel patient on preventing transmission to others • Viral load at this stage is very high ARV medications are not indicated for acute HIV infection

  21. Latent Period • Also known as 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

  22. Symptomatic HIV Infection • Generally occurs when CD4 < 500 • Conditions that may be seen when CD4 count is 200 – 500include: • Generalized lymphadenopathy • Fatigue • Prolonged fevers or diarrhea for > 1 month • Oral or vaginal candidiasis • Bacterial pneumonia • Pulmonary tuberculosis • Herpes zoster (Zona) • Malignancy (Cervical cancer, lymphoma)

  23. 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

  24. 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.

  25. 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

  26. Laboratory Testing in HIV Patients Two common tests used to evaluate and follow HIV patients are: • CD4 cell count • Total Lymphocyte Count (TLC)

  27. CD4 Count (1) • Normal CD4 count in adults is 500-1500 • In children < 5 years old, CD4 count is higher and more variable • Therefore, % CD4 cells is used to follow HIV disease in children

  28. CD4 Count (2) • Best test to measure effect of HIV on immune system • Correlates with risk for developing OIs and risk of death • Can be used to make treatment decisions, e.g.: • When to start prophylactic medications or ARV treatment • Which OIs are most likely when patient has acute symptoms

  29. Total Lymphocyte Count (TLC) (1) • If CD4 testing is not available, TLC and WHO Clinical Staging can be used to: • Estimate level of immunosuppression • Decide when to treat with prophylactic medications and ARV • TLC < 1200 indicates CD4 may be low • Patients considered immune suppressed, need cotrimoxazole prophylaxis when WHO stage 2, 3 or 4

  30. Total Lymphocyte Count (TLC) (2) The Total Lymphocyte Count is easy to calculate from the results of a CBC: TLC = WBC x % Lymphocytes Example: Hb 12.0 65% Neutro Hct 38% 25% Lympho WBC 4,800 9% Mono Plt 165,000 1% Eos What is the TLC?

  31. Key Points • On average, it takes 5-10 years from time of initial HIV infection to become ill or have symptoms • CD4 count is best way to estimate degree of immune suppression • If CD4 testing is not available, TLC and WHO Clinical Staging can be used to evaluate immune system status

  32. Thank you! Questions?

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