hiv

1. HIV/AIDS Donna Sullivan, PhD Division of Infectious Diseases University of Mississippi Medical Center

4. DENDRITIC CELLS, MACROPHAGES, AND HIVNEJM 340:1732 HIV transmitted through sexual activity enters the bloodstream via mucous membranes lining the vagina, rectum and mouth. Macrophages and dendritic cells on the surface of mucous membranes bind virus and shuttle it into the lymph nodes, which contain high concentrations of Helper T cells (CD4 T cells). HIV transmitted through sexual activity enters the bloodstream via mucous membranes lining the vagina, rectum and mouth. Macrophages and dendritic cells on the surface of mucous membranes bind virus and shuttle it into the lymph nodes, which contain high concentrations of Helper T cells (CD4 T cells).

5. HIV-1 LIFE CYCLE

8. THE GENOME OF THE HUMAN IMMUNODEFICIENCY VIRUS (TYPE 1)

12. A schematic representation of the phylogeny of human immunodeficiency virus (HIV) subtypes and simian immunodeficiency virus (SIV) is shown in this diagram. Subtypes of HIV vary in geographic distribution. A schematic representation of the phylogeny of human immunodeficiency virus (HIV) subtypes and simian immunodeficiency virus (SIV) is shown in this diagram. Subtypes of HIV vary in geographic distribution.

15. HIV DIAGNOSTIC TESTING Enzyme linked Immunosorbent Assay (ELISA) Sensitivity and specificity ar >98% Confirmatory testing Western blot, IFA (specificity >99%) Home Testing/Rapid Testing Salivary antibodies Finger stick whole blood

16. An ELISA plate

17. ELISA Activity: ELISA data from three patients

18. Western Blot Analysis

19. Band Pattern Interpretation No bands present Negative Bands at either p31 OR Positive p24 AND bands present at either gp160 OR gp120 Bands present, but pattern does Indeterminate not meet criteriaia for positivity

20. WHEN TO MEASURE HIV RNA AND CD4+ T CELL LEVELS Syndrome consistent with acute HIV infection Initial evaluation of new HIV diagnosis Every 3-4 months in untreated patient Immediately prior to initiating therapy 2-8 weeks after initiating therapy Every 3-4 months in patients on therapy

22. PLASMA HIV RNA - VIRAL LOAD The number of HIV RNA strands in the plasma or serum of an HIV-infected persons measured in logs (10,000 low risk, 100,000 high risk of progression to AIDS) detectable after about 1-2 weeks at about 500 copies

23. CHARACTERISTICS OF PLASMA HIV RNA ASSAYS

26. AIDS DEFINING CONDITIONS (CDC) HIV + test with: CD4 lymphocyte count <200/mm3 OR Opportunistic Infections Oropharyngeal candidiasis Pneumocystis carinii pneumonia (PCP) Disseminated cryptococcal infection CMV disease (retinitis) Progressive multifocal leukoencephalopathy Mycobacterium avium complex, disseminated

27. HIV Has Multiple Steps Available for Attack by Antiretroviral Drugs 1. Viral attachment to CD4 of Helper T cells. 2. Attachment to co-receptor CXCR4 or CCR5. 3. Uncoating. 4. Reverse transcription of viral RNA to form DNA. 5. Synthesis of second strand of DNA. 6. Migration to the nucleus. 7. Integration and transcription of viral DNA. 8. Translation of viral RNA. 9. Viral protease enzyme activation, a site for protease inhibitors to block viral replication. 10. Assembly and budding to form new virus

28. HAART THERAPY Highly Active Anti-Retroviral Therapy Combination of drugs RT inhibitors (nucleoside analogs, non-nucleoside analogs) Protease inhibitors Given when patients CD4+ cells drop below 200

29. ANTIRETROVIRAL DRUGS Ritonavir (Norvir) Saquinivir (Invirase) Indinavir (Crixivan) Amprenivir (Agenerase) Nelfinavir (Viracept) Lopinavir (Kaletra)

31. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs) Zidovudine (AZT, Retrovir) Lamivudine (3TC, Epivir) Didanosine (ddI, Videx EC) Stavudine (d4T, Zerit) Abacavir (Ziagen) Tenofovir (Viread) nucleotide analog Emtricitabine (Coviracil)

32. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) Delavirdine (Rescriptor) Efavirenz (Sustiva) Nevirapine (Viramune)

33. PROTEASE INHIBITORS Nelfinavir (Viracept) Indinavir (Crixivan) Saquinair (Fortovase, Invirase) Ritonavir (Norvir) Lopinavir/ritonavir (Kaletra) Amprenavir (Agenerase) Fosamprenavir (?) Atazanavir (Rayataz)

34. INITIAL TREATMENT: One Choice from Each Column Column A Efavirenz Indinavir Nelfinavir Ritonavir+ Indinavir Ritonavir + Lopinavir* Ritonavir + Saquinavir Column B Didanosine + Lamivudine Stavudine + Didanosine Stavudine + Lamivudine Zidovudine + Didanosine Zodovudine + Lamivudine *Coformulated as Kaletra

35. INDICATIONS FOR INITIATION OF THERAPY: Chronic Infection

36. INDICATIONS FOR INITIATION OF THERAPY: Chronic Infection

38. Estimated proportion of persons surviving, by months after AIDS diagnosis during 1994–2001 and by year of diagnosis—United States

39. PULMONARY INFECTIONS BACTERIA M. tuberculosis M. avium complex S. pneumococcus M. catarrhalis H. influenza P. aeruginosa Nocardia Legionella pneumophila FUNGI Pneumocystis carinii Cryptococcus neoformans Histoplasma capsulatum Coccidiodes immitis Aspergillus fumigatus Penicillium marneffei Candida albicans

40. PULMONARY INFECTIONS VIRUSES Cytomegalovirus Herpes simplex Adenovirus HIV Lymphocytic interstitial pneumonitis (in children) PROTOZOANS Toxoplasma gondii Cryptosporidium Microsporidia TUMORS Kaposi’s sarcoma (HHV8) Non-Hodgkin’s lymphoma

41. Pneumocystis carinii in Lung

42. Pneumocystis carinii Pneumonia: Cavitary Change

43. Gomori Methenamine Silver Stain at High Magnification: P. carinii

44. TB IN AIDS PATIENTS: AFRICA

45. CMV Inclusions in Lung

46. Candida albicans Invasive Process in a Bronchus with H and E Staining

47. C neoformans: Clear capsule surrounding the pale blue nucleus with H and E staining

48. Histoplasma capsulatum

49. Histoplasma capsulatum organisms in macrophages in liver with PAS stain

50. CNS/NEUROLOGIC COMPLICATIONS INFECTIONS T. gondii PML (JC virus) M. tuberculosis C. neoformans CMV HSV-1 HIV Candida albicans NEOPLASMS Primary CNS lymphoma Metastatic Lymphoma Kaposi’s sarcoma UNIDENTIFIED Aseptic meningitis Non-specific gliosis Vascular myelopathy

51. Cryptococcus neoformans In CSF

52. Toxoplasma gondii

53. Progressive multifocal leukoencephalopathy (PML)

54. JC Viral Particles in the Nucleus of an Infected Oligodendrocyte

55. GI COMPLICATIONS BACTERIA Campylobacter jejunii Salmonella Shigella flexnerii Vibrio M. avium complex M. tuberculosis C. difficile Enterotoxigenic E. coli PARASITES Cryptosporidium Isopora belli Microsporidia Entamoeba histolytica Giardia lamblia VIRUSES CMV Adenovirus

56. CMV Infection: Cecal Ulceration

57. Visceral involvement with Kaposi's sarcoma in AIDS is common

58. Mycobacterium avium complex (MAC) Visible Granulomas in the Spleen

59. Kaposi's sarcoma

60. Squamous cell carcinoma Squamous cell carcinoma of the conjunctiva: an unusual cancer, strongly associated with HIV infection. Its incidence has increased markedly in Uganda and Rwanda Squamous cell carcinoma of the conjunctiva: an unusual cancer, strongly associated with HIV infection. Its incidence has increased markedly in Uganda and Rwanda

62. Deaths due to HIV infection, as reported on death certificates, (represented by the red circle on the left) are not exactly the same as deaths of persons with AIDS reported to AIDS surveillance systems of health departments (represented by the blue circle on the right). The crescent shape on the right side of this diagram includes the small percentage of persons with AIDS who die from causes unrelated to HIV infection (such as myocardial infarction, lung cancer, or motor vehicle accidents). Because of improved treatment, survival after diagnosis of AIDS has become longer, which may allow a greater percentage of persons with AIDS to die from other causes. In addition, this crescent includes some persons who die from HIV infection that is falsely not reported as the underlying cause of death on the death certificate. The crescent shape on the left side of this diagram represents the small percentage of persons who do not meet the surveillance criteria for having AIDS among all the persons whose death certificates say they died from HIV infection. The AIDS case definition requires information documenting a low CD4 T-lymphocyte count or diagnosis of one of the 27 AIDS-defining illnesses. Deaths due to HIV infection, as reported on death certificates, (represented by the red circle on the left) are not exactly the same as deaths of persons with AIDS reported to AIDS surveillance systems of health departments (represented by the blue circle on the right). The crescent shape on the right side of this diagram includes the small percentage of persons with AIDS who die from causes unrelated to HIV infection (such as myocardial infarction, lung cancer, or motor vehicle accidents). Because of improved treatment, survival after diagnosis of AIDS has become longer, which may allow a greater percentage of persons with AIDS to die from other causes. In addition, this crescent includes some persons who die from HIV infection that is falsely not reported as the underlying cause of death on the death certificate. The crescent shape on the left side of this diagram represents the small percentage of persons who do not meet the surveillance criteria for having AIDS among all the persons whose death certificates say they died from HIV infection. The AIDS case definition requires information documenting a low CD4 T-lymphocyte count or diagnosis of one of the 27 AIDS-defining illnesses.

78. AIDS Cases in 13- to 19-Year-Olds by Race/Ethnicity, United States AIDS Cases in 13- to 19-Year-Olds, by Race/Ethnicity, United States Black and Hispanic adolescents have been disproportionately affected by the HIV/AIDS epidemic. Although only 15% of the adolescent population in the United States is black, 60% of AIDS cases reported in 1999 among 13- to 19-year-olds were among blacks. Hispanics comprise 14% of the population, 20% of all reported AIDS cases, and 24% of reported adolescent AIDS cases in 1999. These patterns likely will continue since HIV infection also disproportionately affects young black and Hispanic persons. AIDS Cases in 13- to 19-Year-Olds, by Race/Ethnicity, United States Black and Hispanic adolescents have been disproportionately affected by the HIV/AIDS epidemic. Although only 15% of the adolescent population in the United States is black, 60% of AIDS cases reported in 1999 among 13- to 19-year-olds were among blacks. Hispanics comprise 14% of the population, 20% of all reported AIDS cases, and 24% of reported adolescent AIDS cases in 1999. These patterns likely will continue since HIV infection also disproportionately affects young black and Hispanic persons.

80. Estimated rates for adults and adolescents living with HIV infection (not AIDS) or with AIDS (per 100,000 population), 2002—United States

81. Estimated rates for children <13 years of age living with HIV infection (not AIDS) or with AIDS (per 100,000 population), 2002—United States

82. Scope of the epidemic

83. Facts about AIDS In some of the worst-affected countries, 2 or more out of 5 pregnant women in urban areas are infected with HIV. By the end of 1997, 8.2 million children had lost their mother to AIDS before they turned 15. More than 4 million children under the age of 15 have been infected. HIV infection in children progresses more quickly to AIDS, leading to death.

84. Facts about AIDS The vulnerability of girls to HIV infection is exacerbated by denial or neglect of their recognized human rights, including gender discrimination, resulting in inadequate control over their exposure to sexual HIV transmission and poor access to socioeconomic opportunities. Around 1/3 of the 36 million people living with HIV in the world at the end of 1998 are young people aged 15-24.

85. Facts about AIDS In 2000, 5 million people became infected with the virus – more than seven men and women every minute of the day. In societies where the epidemic is heterosexually driven, young women have a higher risk for exposure to HIV than young men, for both physiological and societal reasons. This is especially true for women dependent upon sexual relationships with men for socioeconomic survival.

86. Facts about AIDS (from UNAIDS 1999 World AIDS Campaign and Nature Insight review articles, Nature 410, 968 (01).) Where they have access to appropriate knowledge, skills, and means, today's young people show a remarkable propensity to adopt safer behaviors – better than previous generations or older adults. In Western Europe, some 60% of young people now use condoms the very first time they have sex. A study of young gay men in metropolitan areas of the U.S. found an HIV incidence of 7.2%. Less than 20% of those infected knew of their infection. 41% practiced unsafe sex.

87. Facts about AIDS: Needle Exchange (from UNAIDS 1999 World AIDS Campaign and Nature Insight review articles, Nature 410, 968 (01).) Australia introduced needle and syringe exchange programs and supported changed behavioral norms on needle sharing. HIV prevalence has been less that 0.5% in both men and women who identified themselves as injecting drug users at metropolitan sexual health centers. The corresponding groups in Chicago and New York showed an 18-24% incidence

88. Facts about AIDS: Africa In sub-Saharan Africa, the average prevalence is 8.8% of the population between 15-49 years old. Education has been very effective in some countries. In Zambia, HIV prevalence for women under 20 attending antenatal clinics in Lusaka declined from 27% in 1993 to 17% by 1999. Life expectancy in Africa rose from 44 years in 1950 to 59 years by the late 80s, and is now expected to return to under 45 years.