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HIV/AIDS

31 st Annual Winter Update Indiana Osteopathic Association December 7, 2012 Indianapolis, IN cgenske@ecommunity.com. HIV/AIDS. Outline. History Epidemiology Transmission Natural History Testing Recommendations Diagnosis Clinical Manifestations Treatment Health Maintenance

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HIV/AIDS

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  1. 31st Annual Winter Update Indiana Osteopathic Association December 7, 2012 Indianapolis, IN cgenske@ecommunity.com HIV/AIDS

  2. Outline • History • Epidemiology • Transmission • Natural History • Testing Recommendations • Diagnosis • Clinical Manifestations • Treatment • Health Maintenance • Hot Topics • Pre-exposure prophylaxis (PrEP) • Post-exposure prophylaxis (PEP)

  3. History

  4. June 5, 1981: MMWR published 5 cases of PCP in homosexual men from California • July 3, 1981: 26 additional cases • Dec 10, 1981: 3 NEJM papers describe cases

  5. July 1981 41 cases Kaposi’s Sarcoma (KS) GRID = Gay-related Immune Deficiency 1982 June 1982 20 states with disease July 1982 AIDS = Acquired ImmunoDeficiency Syndrome Dec 1982 Hemophiliacs died 1292 of 3064 people died 1983 James Mason isolated LAV Robert Gallo isolated HTLV-III April 1984 1985 March 1985 First test to identify HIV antibodies developed

  6. Rock Hudson died of AIDS 1985 50% of hemophiliacs infected 1986 Surgeon General’s first report on AIDS 1986 1986 Drug trials begin (ACTG) March 1987 FDA approved first drug (AZT) 45,000/83,000 patients had died 1988 April 1990 Ryan White died FDA approved second drug (ddI) 1991

  7. Ryan White CARE Act passed 1990 AZT reduces MTCT 1994 2 drugs are better than 1 1994 First HIV viral load testing 1995 1996 HAART in use (3+ drugs) First one pill once daily regimen approved 2006 DHHS guidelines recommend initiation of ART for CD4 <500 2009 2010+ New hope for HIV prevention (PrEP)

  8. AIDS Mortality Rates: 1995-2001 Mortality vs. ART utilization 100 40 35 USE OF ART 30 75 25 DEATHS Percentage of patient-days on ART 20 50 Deaths per 100 person-years 15 10 25 5 0 0 1995 1996 1997 1998 1999 2000 2001 Courtesy: AETC

  9. Epidemiology

  10. Adult HIV Prevalence, 2010 Courtesy: UNAIDS

  11. Courtesy: UNAIDS

  12. Courtesy: UNAIDS

  13. Changes in HIV Incidence, 2001-2010

  14. Epidemiology – Worldwide • 34 million living with HIV / AIDS • ~2/3 in Sub-Saharan Africa, mostly heterosexual • 60% unaware of being infected • 7,000 new infections each day (2.5 million/yr) • 900 of these are children < 15 yo • 47% in women • 39% in young people (15-24) • African Americans 8x rate of HIV cases compared to whites • 1.7 million died in 2011 • Only 25% are receiving treatment !! www.unaids.org

  15. Epidemiology – U.S. • 1,180,000 HIV+ (1 in 200) • 20% undiagnosed • 488,000 living w/ AIDS • 21,000 die each yr • 50,000 newly infected each yr • 61% MSM • 1 of every 5 homosexual urban males HIV+ • 1 of every 22 African Americans will be infected • Incidence in Washington D.C. is 3%!

  16. Epidemiology – U.S. • Only 1 of 5 have undetectable virus -> (close to) non-contagious. • Over 800,000 have detectable virus -> CONTAGIOUS! • Individuals unaware of their HIV+, particularly those recently infected, are major contributors to the ongoing epidemic

  17. Epidemiology – Indiana • Persons living with HIV/AIDS in Indiana as of June, 30, 2012 • Total = 10,420 • 80% Male (8,388) • 20% Female (2,032) • Race/Ethnicity of HIV patients • 53% White (5,541) 0.1% infected • 36% Black (3,764) 0.6% infected • 7% Hispanic (780) 0.2% infected Spotlight on HIV/STD/Viral Hepatitis, Indiana Semi-Annual Report, June 2012: http://www.in.gov/isdh/files/At_A_Glance-Dec.pdf Indiana IN Depth Profile. http://www.stats.indiana.edu/c2010/dp1/FactfinderINandUS.pdf

  18. Transmission

  19. HIV Transmission/Acquisition • Found in blood, semen, or vaginal fluid of an infected person • HIV is transmitted/acquired by: • Having sex (anal, vaginal, or oral) with someone infected with HIV • Sharing needles, syringes with someone who has HIV • Exposure (in the case of infants) to HIV before or during birth, or through breast feeding

  20. Probability of HIV Transmission INFECTION ROUTERISK OF INFECTION Sexual Intercourse Male-to-male transmission 1 in 10 - 1 in 1,600 Male-to-female transmission 1 in 200 - 1 in 2,000 Female-to-male transmission 1 in 700 - 1 in 3,000 Transmission from mother to infant Without AZT 1 in 4 With AZT Less than 1 in 10 With HAART 1-2 in 100 Other Transfusion of infected blood 95 in 100 Needle stick 1 in 250 Needle sharing 1 in 150 Royce, et al

  21. Natural History

  22. Natural History • Acute Infection (days to weeks) • Partial Control of HIV (weeks to months) • Asymptomatic HIV Infection (1-10+ years) • Symptomatic HIV Infection & AIDS (years)

  23. Natural History of HIV Infection Primaryinfection 1200 1100 1000 900 800 700 600 500 400 300 200 100 0 Death Possible acute HIV syndrome Wide dissemination of virus Seeding of lymphoid organs Opportunisticdiseases 10E7 10E6 10E5 10E4 10E3 Clinical latency CD4 T Cells/mm3 Constitutionalsymptoms Viremia (copies/mL plasma) 6 3 9 10 1 6 7 8 9 12 11 0 2 5 4 3 Weeks Years

  24. CD4 Lymphocyte Count • Reflects immune status • Normal CD4 count: 500 - 1,500 cells/mm3 • CD4 count decreases as HIV disease progresses • CD4 counts differ daily • Overall trend of CD4 counts over time most important • CD4 < 200 = AIDS (or opportunistic infection)

  25. HIV Viral Load • Number of HIV RNA copies per mL of blood • “High” viral load: 5,000 to >1,000,000 copies • High reproduction rate • Disease will progress faster • “Low” viral load: 200 to 500 copies • Low reproduction rate • Risk of disease progression is low • “Undetectable” viral loads: <50 or <400 • Below the threshold needed for detection

  26. 2006 CDC HIV Testing Recommendations Testing Recommendations

  27. CDC Testing Guidelines, 2006 • Offer routine testing in all health care settings to: • 13- to 64-year-olds • Anyone with Tuberculosis (TB) • All patient seeking treatment for STDs • All pregnant females • Any health care worker exposed to blood or body fluids • Anyone who requests testing

  28. CDC Testing Guidelines, 2006 • Who should be tested at least annually? • IVDA and their sex partners • Persons who exchange sex for money or drugs • Sex partners of HIV-infected persons • Persons with multiple sex partners

  29. Why emphasize early diagnosis? • Individuals unaware of their HIV+, particularly those recently infected, are major contributors to the ongoing epidemic • Earlier treatment: • Lowers mortality • “Delayed Therapy” group (<500) had 94% higher mortality!* • Decreases risk of transmission by 96%** • May improve immune system by (partially) restoring CD4 count more towards normal • May lower long-term complications associated w/ inflammation (though biomarkers of inflammation may never return to normal ) *Kitahata et al **Cohen et al

  30. Diagnosis

  31. Diagnosis • Screening: ELISA antibody (or other rapid tests) • Now recommended to be part of routine medical care (yearly if high risk) • Time to + : ~ 3 wks • Newer assays may detect infection as early as 10 - 14 days; still, very early infection will not be detectable • Confirmation: Western Blot • Time to + : ~4-5 weeks • Any two: p24, gp41, gp120/160 -> positive • One + band, or other + bands -> “indeterminate” • Either wait and repeat, or obtain quantitative assay for HIV by PCR = “viral load”

  32. Some causes of False-Negative HIV Antibody Tests • Acute HIV Infection • Advanced HIV Infection • Antiretroviral Therapy

  33. Some causes of False-Positive HIV Antibody Tests • Liver Disease • Autoimmune Disorders • CKD/ESRD • Congenital bleeding disorders • Recent Infection with dengue, malaria, hepatitis B, leprosy • Immunizations

  34. Diagnosing Acute HIV: Window Period Window Period = Time between infection and detectable HIV antibodies Courtesy: AETC

  35. Diagnosing Acute HIV: Acute HIV Acute HIV Acute HIV = patients may present with acute retroviral syndrome/illness

  36. Laboratory Diagnosis of Acute HIV Acute HIV • Positive HIV-1 RNA Assay • Negative HIV Antibody Test

  37. Clinical Manifestations

  38. Course of HIV Infection • Chronic and progressive infection • Acute Retroviral Syndrome (Acute Infection) • Flu-like symptoms • Period of active viral replication • HIV Ab levels may be below the limit of detection (negative ELISA), however the patient is HIGHLY CONTAGIOUS!

  39. Acute Retroviral Syndrome • 80 - 90% with acute HIV infection report symptoms consistent with acute retroviral syndrome • “Mononucleosis-like” syndrome • Onset of symptoms typically 2-4w after exposure • Median duration of symptoms is 2 weeks • Fever (96%), adenopathy (74%), pharyngitis (70%), rash (70%), myalgia (59%), night sweats (50%), thrombocytopenia (45%), leukopenia (45%), diarrhea, headache • May also present as “aseptic/viral meningitis”

  40. Acute Retroviral Syndrome • Most acutely infected patients seek medical attention • This syndrome may be missed in up to 75% of presenting patients • HIV antibody levels usually negative • Check HIV RNA PCR

  41. Course of HIV Infection • Asymptomatic Phase (6 months - >10 years) • Host immune response controls viral replication • CD4 cell count gradually declines • Symptomatic Phase • Host immune response begins to wane • CD4 cell count < 500 cells • Bacterial pneumonia, thrush, vaginal candidiasis, shingles, oral leukoplakia • CD4 cell count < 200 cells • Opportunistic infections • Pneumocystis jirovecii pneumonia, CMV retinitis, Candida esophagitis, Toxoplasma encephalitis, Histoplasmosis, Cryptococcal meningitis, MAC, lymphoma, etc

  42. CD4 Count & Risk of Clinical Disease

  43. General Generalized LAD Thrombocytopenia (ITP) Elevated total protein Dermatologic Seborrheic dermatitis Zoster (shingles) Superficial fungal infections Warts Eosinophilic folliculitis Mucocutaneous Oropharyngeal candidiasis Oral or genital herpes Gingivitis/peridontitis Oral Hairy Leukoplakia Respiratory Recurrent sinusitis Community acquired pneumonia Tuberculosis Clinical Findings in HIV Infection

  44. Images courtesy of: AIDS Images Library www.aidsimages.ch

  45. Images courtesy of: AIDS Images Library www.aidsimages.ch

  46. Other clues to possible HIV • Unusual presentation of a common illness • Pneumococcal pneumonia w/ bacteremia in a young person • Salmonella, shigella, campylobacter bacteremia • Presentation of an unusual illness • More advanced/severe dx than expected • Unusual age for illness • TB, especially w/ unusual presentation • Other STDs

  47. Other clues to possible HIV • Common complaints • Persistent fatigue, recurrent fevers, chills/night sweats, persistent diarrhea, weight loss • Routine lab abnormalities • Leukopenia (low WBC) • Lymphopenia (low lymphocytes) • Thrombocytopenia (low platelets) • Mild transaminitis • Elevated protein

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