HIV Disease/AIDS

Part One

© Hanuš Rozsypal

Historical Chronology | Epidemiology | Etiology and Pathogenesis | Clinical Manifestations

Historical Chronology

Year  Discovery 
1940-50 Origin of HIV in West Africa (jumping the species barrier)
1981 Gottlieb, Friedman-Kien - initial case reports (Kaposi´s sarcoma, Pneumocystis carinii pneumonia), AIDS was first recognized as a new and distinct clinical entity
1982 CDC created first definition of AIDS
1983-84 Montagnier et al. - detection of causative agent - HIV (formerly HTLV III/LAV)
1985 First antiretroviral - zidovudine (ZDV, formerly AZT)
1986 Montagnier et al. discovered HIV-2
1995 First protease inhibitor was approved for use in combination with other nucleoside analogue
1996 Reduced incidence of AIDS cases in USA

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Epidemiology

Global HIV/AIDS Epidemiology


Global estimates of the HIV/AIDS by the end of 2009 (in millions) (UN AIDS, WHO)

People Adults Children Total
Living with HIV/AIDS 30.8 [29,2-32.6] 2.5 [1.6-3.4] 33.3 [31.4-35.3]
Newly infected with HIV during 2009 2.2 [2.0-2.4] 0.37 [0.23-0.51] 2.6 [2.3-2.8]
AIDS related deaths during 2009 1.6 [1.4-1.8] 0.26 [0.15-0.36] 1.8 [1.6-2.1]

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Etiology and Pathogenesis

Etiologic agent: Human Immunodeficiency Virus (HIV)


Structure of the HIV


Structure of an HIV virion particle
Genetic diversity of the HIV
  • Types:
          - HIV-1
          - HIV-2
  • Groups of the HIV-1:
          - M (major)
          - O (outlier)
          - N (novel)
  • Subtypes (clades) of group M:
          - A-G

    Pathogenesis


    CD4 glycoprotein on T cells - primary receptor od HIV
    Viral replication is very rapid during all stages of the HIV infection.
    Infection of CD4+ T ly´s is crucial for evolving of IDS.
    Depletion of CD4+ T ly´s is a laboratory hallmark of the destruction of immune system during HIV infection
    CD4+ cell count – dynamic marker to response to Rx

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    • Clinical Manifestations

    Clinical Manifestations and Classification of HIV Disease


    Natural History of HIV Infection
  • Incubation period: 2-6 weeks
  • Primary HIV infection (>50%)
  • Early stage of HIV disease (asymptomatic infection, PGL)
  • Intermediate stage of HIV disease (including ARC)
  • Late stage of HIV disease (AIDS, including advanced HIV disease and terminal HIV disease)

    Classification of HIV Infection


    Classification System
    1993 Revised CDC HIV Classification System for adults and adolescents

    Clinical categories

    Clinical category
    		      Defining conditions
    A
    • Asymptomatic HIV infection
    • Persistent generalized lymphadenopathy (PGL)
    • Acute (primary) HIV illness
    B
    • Fever of >38.5°C >1 month
    • Diarrhea >1 month
    • Oropharyngeal candidosis
    • Vulvovaginal candidosis (persistent >1 month or poorly responsive to therapy)
    • Herpes zoster recurrent or multidermatomal
    • Oral hairy leukoplakia
    • Lymphoid interstitial pneumonitis
    • Cervical dysplasia or carcinoma in situ
    • Pelvic inflammatory disease (PID)
    • Listeriosis
    • Bacillary angiomatosis
    • Thrombocytopenic purpura
    • Peripheral neuropathy
    C (AIDS)
    • Pneumocystis jiroveci pneumonia
    • Cerebral toxoplasmosis
    • Candidiasis esophageal, tracheal, bronchial or pulmonary
    • Herpes simplex with mucocutaneous ulcer >1 month, esophagitis, bronchitis, pneumonia
    • CMV retinitis
    • Generalized CMV infection (in other organs than liver, spleen, nodes)
    • Progressive multifocal leukoencephalopathy
    • Recurrent pneumonia (with >2 episodes in 12 months)
    • Recurrent Salmonella bacteremia
    • Chronic intestinal cryptosporidiosis (diarrhea >1 month)
    • Chronic intestinal isosporiasis (diarrhea >1 month)
    • Extrapulmonary cryptococcosis
    • Disseminated or extrapulmonary histoplasmosis
    • Disseminated coccidioidomycosis
    • Tuberculosis (pulmonary or extrapulmonary)
    • Disseminated or extrapulmonary M. avium or M. kansasii infection
    • Kaposi´s sarcoma
    • Lymphomas (Burkitt´s, immunoblastic, primary in brain)
    • Invasive cervical cancer
    • HIV encephalopathia
    • Wasting syndrome


    Laboratory categories


    Laboratory category
    CD4+ lymphocyte count
    absolute (/ml)
    relative (%)
    1
    >500
    >28
    2
    200-500
    14-28
    3
    <200
    <14


    Pulmonary Diseases


    Pneumocystis jiroveci Pneumonia
    Causative agent: fungal organism P. jiroveci
    3 typical symptoms:
       -dry cough
       -increasing dyspnea
       -fever
    Lab: O2, LD, CD4+
    X-ray: bil. intersticial shadowing (central parts of the lung fields)
    HRCT: ground glass attenuation
    Specimen collection (induced sputum, BAL): trophozoites + cysts
    Rx: cotrimoxazol, pentamidine, …
    Prophylaxis: primary CD4+ <200/ml, secondary after PcP



    Pneumocystis pneumonia - X ray

    Pneumocystis pneumonia - HRCT

    Pneumocystis jiroveci - cysts


    Other Pulmonary Diseases
  • Bacterial and viral pneumonia
  • Pulmonary tuberculosis
  • Lymphomatoid interstitial pneumonitis (LIP) - children

    Orogastrointestinal Diseases


    Diseases in the Oral Cavity




    Oropharyngeal candidiasis (thrush)

    Oral hairy leukoplakia

    Oral Kaposi sarcoma


    Gastrointestinal Diseases
  • Candidal oesophagitis
  • CMV or HSV oesophagitis
  • Intestinal infections caused by
          - common pathogens (Salmonella, Campylobacter etc.)
          - oportunistic organisms (Cryptosporidium, microsporidia)
  • HIV enteropathy

    Nervous System Diseases


    Involvement of Nervous System
    Nervous system can be affect by
  • both direct and indirect effects of HIV of CNS
          (HIV-encephalopathy = HIV-associated cognitive/motor complex + AIDS dementia complex [ADC])
  • opportunistic infections (BT, cryptococcal meningitis, PML)
  • neoplasms (primary cerebral lymphoma)
  • unknown mechanisms (polyneuropathy)

    Brain Toxoplasmosis
    Focal encephalitis caused by Toxoplasma gondii
    Clinical presentation ranges from focal neur. finding to generalized symptoms – confusion, seizures
    CT: hypodense single or multiple lesions, ring enhancement, surrounding edema
    Serologic testing – reliable
    Rx: pyrimethamin, sulphadiazin, clindamycin



    Brain toxoplasmosis - CT

    Brain toxoplasmosis - MRI

    PML - CT






    Primary brain lymphoma - CT

    Primary brain lymphoma - autopsy

    Cryptococcus neoformans in the CSF


    Ocular Diseases


    CMV Retinitis

    CMV: reactivation of latent infection that manifests in pts with
    CD4+ <50/ml
    Visual field deficits can spread and lead to blindness
    Dg.: fundoscopic
    Rx: anti-CMV agents

    Wasting Syndrome and Metabolic Disorders


    Wasting Syndrome
  • Wasting syndrome = substantial reduction in body weight
  • Before the advent of HAART, up to 10% of HIV+ individuals fulfilled CDC definition of AIDS because of wasting
  • In 90s – we expected wasting syndrome – as a typical face of the AIDS of the 21st century



    CMV retinitis - fundoscopy

    Wasting syndrome

    Cutaneous Kaposi sarcoma - solitary lesions


    Lipodystrophy
  • Abnormalities of lipid metabolism and body fat distribution
          - central fat accumulation (PI)
          - peripheral lipoatrophy (NRTI)
  • Hypercholesterolaemia
  • Hypertriglyceridaemia
  • Increased risk of cardiovascular diseases



    Lipodystrophy - accumulation of the dorsocervical visceral fat ("buffalo hump")

    Lipodystrophy - accumulation of the visceral fat

    Lipoatrophy - loss of buccal fat


    Skin Diseases


  • Seborrhoic dermatitis
  • Pyodermias
  • Progressive chicken-pox
  • Recurrent and persistent herpes simplex
  • Herpes zoster (shingles)
  • Dermatomycoses
  • Allergic rash



    Rosacea

    Seborrheic dermatitis

    Anal condylomata acuminata


    Disseminated Infections


  • Bacterial sepsis (Salmonella)
  • Disseminated mycobacteriosis (Mycobacterium avium)
  • Generalized CMV infection
  • Disseminated tuberculosis
  • Disseminated mycoses (cryptococcosis, histoplasmosis)
  • DD: NH lymphoma

    Tumors associated with HIV


    AIDS-Indicator Tu´s
  • Kaposi´s sarcoma
  • NH lymphoma
  • Primary cerebral lymphoma
  • Invasive cervical cancer

    Other tumors associated with HIV
  • Hodgkin´s disease
  • Invasive anal cancer
  • Multiple myeloma
  • Leucemias
  • Lung adenocarcinoma
  • Leiomyosarcoma (of children)



    Oral Burkitt´s lymphoma

    Kaposi sarcoma on the plant

    Extensive progression of the Kaposi sarcoma


    Important Co-morbidities




  • Viral hepatitis
  • Syphilis



    Genital primary syphilis (ulcus durum)

    Secondary syphilis (roseola syphilitica)

    Secondary syphilis

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    • Literature
    1. EACS (European AIDS Clinical Society) Guidelines, version 6 - October 2011. Online: www.europeanaidsclinicalsociety.org
    2. Hoffmann C, Rockstroh JK: HIV 2011. Medizin Fokus Verlag, Hamburg, 2011. Online: www.hivbook.com
    3. Saag MS, Chambers HF, Eliopoulos GM, Gilbert DN, Moellering Jr RC. The Sanford Guide to HIV/AIDS Therapy 2012. 20th edition, Sperryville, VA, USA, 2012. Online: www.sanfordguide.com



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    © H. Rozsypal, updated on March-4-2012