HIV

1. HIV • “Human Immunodeficiency Virus” • A specific type of virus (a retrovirus) • HIV invades the helper T cells to replicate itself.

2. AIDS • Acquired Immunodeficiency Syndrome • HIV is the virus that causes AIDS • Disease limits the body’s ability to fight infection due to a very weak immune system

3. HIV virus • Discovered independently by Luc Montagnier of France and Robert Gallo of the US in 1983-84. • Former names of the virus include: • Human T cell lymphotrophic virus (HTLV-III) • Lymphadenopathy associated virus (LAV) • AIDS associated retrovirus (ARV)

4. AIDS: A Leading Cause of Death Among People Aged 25-44 years Deaths per 100,000 people aged 25-44 years

5. Characteristics of the virus • Icosahedral (20 sided), enveloped virus of the lentivirus subfamily of retroviruses. • Retroviruses transcribe RNA to DNA. • Two viral strands of RNA found in core surrounded by protein outer coat. • Outer envelope contains a lipid matrix within which specific viral glycoproteins are imbedded. • These knob-like structures responsible for binding to target cell.

6. HIV structure

7. HIV - virus • HIV is a lentivirus - an RNA virus from the class of retroviruses • 2 HIV species (1 and 2) - 40-50% homologous • Several HIV clades - A,B,C,D,A/E,O (others) - 70-80% homologous • Within a clade - 85-90% homologous • Within an individual - >95% homologous • About 109 viruses produced per day, error-prone reverse transcriptase (q 10-4-10-5)

8. HOW IS HIV SPREAD? Transmission of AIDS • Sexual contact with infected individual: homosexual and heterosexual. 75% of transmission.

9. Transmission of AIDS 2. PARENTERAL. • Sharing of unsterilized needles by intravenous drug users unsafe medical practices, ear piercing, or tattooing equipment 5-10% of transmission. • Transfusions and Blood Products: Hemophiliac population was decimated in 1980s. Risk is low today. 3-5% of transmission • Transplantation of infected tissues or organs

10. Transmission of AIDS 3.Mother to Infant (Perinatal): 25% of children become infected in utero, during delivery, or by breast-feeding (with AZT only 3%). 5-10% of transmission. • Before Birth • During Birth • Postpartum • After the birth

11. HIV INFECTION CYCLE • I - ATTACHMENT/ENTRY • II - REVERSE TRANSCRIPTION • III - DNA INTEGRATION • IV - REPRODUCTION OF HIV

14. Definition of AIDS The blood CD4+ T cell count drops below 200 cells/mm3 in the HIV-infected patients. AIDS is the result of the persisting infection by HIV.

15. Pathogenesis and Immunological features • the decline of Th cells， • the depletion and loss of function of Th cells • polyclonal activation of the B cells • increased levels of the IL-1 and TNF-a • Decreased number of the NK cells， • increased incidence of malignant tumor、 • virus infection

16. Primary HIV Syndrome • Symptoms are relatively nonspecific. • HIV antibody test often negative • but becomes positive within 3 to 6 months, this process is known as seroconversion. • Large amount of HIV in the peripheral blood. • Primary HIV can be diagnosed using viral load titer assay or other tests. • Primary HIV syndrome resolves itself and HIV infected person remains asymptomatic for a prolonged period of time, often years.

17. Primary HIV Syndrome • Mononucleosis-like, cold or flu-like symptoms may occur 6 to 12 weeks after infection. • lymphadenopathy • fever • rash • headache • Fatigue • diarrhea • sore throat • neurologic manifestations. • no symptoms may be present

18. HIV INFECTION HIV infection may have NO SYMPTOMS, sometimes for 5 to 10 years. May have flu-like symptoms, which may be ignored: fever loss of appetite night sweats diarrhea swollen glands skin rashes WINDOW PERIOD: 6 to 12 weeks (or longer) before HIV antibodies are produced. Person may be HIV infected but their blood test is negative. (false negative)

19. HIV / AIDS SYMPTOMS Later symptoms of HIV infection, and then AIDS: • Significant weight loss • Lack of resistance to infection • Dry couch or shortness of breath • Furry white spots in the mouth • Red or purplish spots on the body • Memory or movement difficulties

20. HARMFUL EFFECTS of HIV HIV destroys cells in the immune system, leaving them unable to fight off diseases which most healthy people can resist. • These “opportunistic infections” that take advantage of the body’s weakened defenses include: • Fungi (yeast / thrush, cryptococcus / brain) • Parasites (pnuemocystis / pnuemonia) • Viruses (systemic herpes, shingles, CMV) • Bacteria (tuberculosis) :HIV can infect and disrupt many cells in the body brain, heart, lungs, kidneys, liver, intestines.

21. Clinical features Latent period：6 month—4 year Infection phase：influenza-like symptom、infectious Abs production：3-20 weeks symptom：AIDS related complex ARC （1) opportunistic infections （2) malignant tumors： Kaposi’s sarcoma、malignant lymphoma （3)abnorm of the central nervous system

22. HIV - clinical progression

23. AIDS • CD4 count drops below 200 person is considered to have advanced HIV disease • If preventative medications not started the HIV infected person is now at risk for: • Pneumocystis carinii pneumonia (PCP) • cryptococcal meningitis • toxoplasmosis • If CD4 count drops below 50: • Mycobacterium avium • Cytomegalovirus infections • lymphoma • dementia • Most deaths occur with CD4 counts below 50.

25. Immune time course post infection

26. Antibody Levels, T Cell Counts, and HIV Concentration After Infection

27. Candida • Candida species are ubiquitous fungi found throughout the world as normal body flora. • Candidiasis can range from superficial disorders such as diaper rash to invasive, rapidly fatal infections in immunocompromised hosts. • Candida albicansis commonly responsible for candidiasis. • Candida tropicalis,Candida parapsilosis,Candida guilliermondi, and Torulopsis glabrata are also causative organisms

28. edcenter.med.cornell.edu rad.usuhs.mil/medpix/ medpix.html

29. http://tray.dermatology.uiowa.edu www.dermnet.com

30. Respiratory system • Pneumocystis Carinii Pneumonia (PCP) • Tuberculosis (TB) • Kaposi's Sarcoma (KS) • Gastro-intestinal system • Cryptosporidiosis • Candida • Cytomegolavirus (CMV) • Isosporiasis • Kaposi's Sarcoma • Central/peripheral Nervous system • Cytomegolavirus • Toxoplasmosis • Cryptococcosis • Non Hodgkin's lymphoma • Varicella Zoster • Herpes simplex • Skin • Herpes simple • Kaposi's sarcoma • Varicella Zoster

31. Disseminated Zoster • Disseminated zoster (Varicella – Zoster) seen in immunocompromised patients. • hematogenous spread: • results in the involvement of multiple dermatomes. • Visceral involvement. • can lead to death due to encephalitis, hepatitis, or pneumonitis.

32. Disseminated Zoster

33. CMV • CMV is a member of the herpesvirus group • Transmission: • Transmission occurs from person to person. • Infection requires close, intimate contact with a person excreting the virus: • saliva, urine, breast milk, transplanted organs, and rarely from blood transfusions and other body fluids • Sexual transmission has been documented • There is no known animal reservoir • In most adults, reactivation, is the cause of symptomatic disease

34. CMV

35. Laboratory Diagnosis of HIV Infection • Methods utilized to detect: • Antibody • Antigen • Viral nucleic acid • Virus in culture

36. Laboratory Tests for HIV screen for HIV1 and HIV2 • Enzyme-Linked Immunosorbent Assay/Enzyme Immunoassay (ELISA/EIA) • Radio Immunoprecipitation Assay/Indirect Fluorescent Antibody Assay (RIP/IFA)

37. Laboratory Tests for HIV • Confirmatory western blot • Polymerase Chain Reaction (RT-PCR) qualitative for HIV1 • HIV viral load in serum • HIV genotype: predicts resistance to drugs • HIV phenotype: measures resistance to drugs • CD4 and CD8 counts

38. Detection of p24 HIV antigen • The p24-antigen screening assay is an EIA performed on serum or plasma. • P24 antigen only present for short time, disappears when antibody to p24 appears. • Anti-HIV-1 bound to membrane, incubated with patient serum, second anti-HIV-1 antibody attached to enzyme label is added (sandwich technique), color change occurs. • Optical density measured, standard curve prepared to quantitate results.

39. Detection of p24 HIV antigen • Positive confirmed by neutralizing reaction, preincubate patient sample with anti- HIV, retest, if p24 present immune complexes form preventing binding to HIV antibody on membrane when added. • Test not recommended for routine screening as appearance and rate of rise are unpredictable. • Sensitivity lower than ELISA.

40. Polymerase Chain Reaction (PCR) • Looks for HIV DNA in the WBCs of a person. • PCR amplifies tiny quantities of the HIV DNA present, each cycle of PCR results in doubling of the DNA sequences present. • The DNA is detected by using radioactive or biotinylated probes. • Once DNA is amplified it is placed on nitrocellulose paper and allowed to react with a radiolabeled probe, a single stranded DNA fragment unique to HIV, which will hybridize with the patient’s HIV DNA if present. • Radioactivity is determined.

41. Viral Load Tests • Viral load or viral burden is the quantity of HIV-RNA that is in the blood. • RNA is the genetic material of HIV that contains information to make more virus.

42. Viral Load Tests • Viral load tests measure the amount of HIV-RNA in one milliliter of blood. • Take 2 measurements 2-3 weeks apart to determine baseline. • Repeat every 3-6 months in conjunction with CD4 counts to monitor viral load ant T-cell count. • Repeat 4-6 weeks after starting or changing antiretroviral therapy to determine effect on viral load.