HIV Disease/AIDS

Part One

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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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


    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
    • Asymptomatic HIV infection
    • Persistent generalized lymphadenopathy (PGL)
    • Acute (primary) HIV illness
    • 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 (%)

    Pulmonary Diseases

    Pneumocystis jiroveci Pneumonia
    Causative agent: fungal organism P. jiroveci
    3 typical symptoms:
       -dry cough
       -increasing dyspnea
    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

  • 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


    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:
    2. Hoffmann C, Rockstroh JK: HIV 2011. Medizin Fokus Verlag, Hamburg, 2011. Online:
    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:

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