HIV Diseases Spectrum

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HIV Diseases Spectrum

• Dr.Dilip Mathai MD,FCAMS,FICP,FIDSA
• Professor and Head
• Dept of General Medicine Unit 1 and Infectious
  Diseases
• Christian Medical College, Vellore, India

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(No Transcript)
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HIV Diseases Spectrum

• Mechanisms of illness in HIV-infected patients
• Directly related to HIV
• Due to HIV-induced immunosuppression
• Due to antiretroviral therapy or other therapies
• Due to co-morbid or unrelated illnesses
• Staging Systems for HIV Infection
• HIV-related diseases by clinical syndrome

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HIV Diseases Spectrum

• Mechanisms of illness in HIV-infected patients
• Directly related to HIV
• Due to HIV-induced immunosuppression
• Due to antiretroviral therapy or other therapies
• Due to co-morbid or unrelated illnesses
• Staging Systems for HIV Infection
• HIV-related diseases by clinical syndrome

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Illnesses Directly Related to HIV

• Primary HIV infection
• Constitutional signs and symptoms fever, chills,
  night sweats, anorexia, weight loss
• HIV dementia
• HIV neuropathy
• Idiopathic Thrombocytopenic Purpura (ITP)

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Primary HIV Infection

• Acute febrile illness frequently seen with
  acquisition of HIV infection
• Classic definition mononucleosis-like illness
  with or without aseptic meningitis associated
  with seroconversion to HIV
• Typically occurs 2-4 weeks after HIV exposure
• Occurs in over 50 of patients although it is
  frequently unrecognized

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Common Signs and Symptoms of Primary HIV
Infection

• fever 77
• fatigue 66
• maculopapular rash 56
• myalgia 55
• headache 51
• pharyngitis 44
• cervical nodes 39

• arthralgia 31
• oral ulcers 29
• odynophagia 28
• weight loss 24
• diarrhea 23
• oral candidiasis 17
• photophobia 12

Clin Inf Dis 199724965
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Laboratory Findings in Primary HIV Infection

• General lab testing
• Leukopenia with atypical lymphocytes
• Mildly elevated transaminases
• Evidence of aseptic meningitis on LP
• HIV-specific lab testing
• initial antibody testing (ELISA) may be negative
  and may need to be repeated
• HIV plasma RNA testing (the viral load) and other
  tests for the virus (e.g. p24 antigen) will be
  positive before antibody tests

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27 year old male admitted 3/17/88 with fever,
diarrhea, and encephalopathy with coma HIV
seroconversion by Western Blot
Control
- Control
Screening
Admission
2 wks later
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HIV Encephalopathy

• Also known as HIV dementia or AIDS-related
  dementia
• WHO definition clinical findings of disabling
  cognitive and/or motor dysfunction interfering
  with activities of daily living, progressing over
  weeks to months, in the absence of a concurrent
  illness or condition, other than HIV infection,
  which could explain the findings
• Associated with advanced disease
• Responsive to antiretroviral therapy

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HIV Peripheral Neuropathy

• Symmetric sensory polyneuropathy
• Most common in lower extremities, beginning
  distally
• Associated with advanced HIV disease
• Responsive to antiretroviral therapy
• Differential diagnosis the D drugs, B-12
  deficiency, diabetes, alcohol

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Idiopathic Thrombocytopenic Purpura

• Isolated thrombocytopenia related to peripheral
  destruction of platelets
• Seen more commonly in earlier HIV infection
• Bleeding episodes relatively rare
• Responsive to antiretroviral therapy,
  corticosteroids, splenectomy, and anti-Rh antibody

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HIV Diseases Spectrum

• Mechanisms of illness in HIV-infected patients
• Directly related to HIV
• Due to HIV-induced immunosuppression
• Due to antiretroviral therapy or other therapies
• Due to co-morbid or unrelated illnesses
• Staging Systems for HIV Infection
• HIV-related diseases by clinical syndrome

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Pathogenesis of HIV Infection

• HIV targets the CD4 T lymphocyte, replicating
  in and killing the cell
• CD4 cell loss leads to a progressive weakening of
  the immune system
• The weakened immune system leaves the patient
  susceptible to serious infections and
  malignancies
• The individual and cumulative consequences of
  these infections and malignancies lead to
  progressive debility and death

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HIV Progression Relative to CD4 Lymphocyte Count
CD4 cell count / mm 3
Bacterial skin infection Herpes simplex,
zoster Oral, skin fungal infections
800
Thrombocytopenia Lymphadenopathy
600
Kaposis sarcoma
500
300
400
400
200
Hairy leukoplakia Tuberculosis
Lymphoma
200
PCP
Cryptococcosis Toxoplasmosis
CMV
100
MAC
0
Months
Years
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Thrush
17
CNS Toxoplasmosis
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HIV-Related Malignancies

• AIDS-Defining
• Non-Hodgkins lymphoma
• Kaposi Sarcoma
• Higher incidence in HIV but not AIDS-defining
• Hodgkins Disease
• Lung Cancer
• Anorectal Cancer
• Malignant Melanoma

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Potential Clinical Clues to Underlying HIV
infection

• weight loss
• generalized lymphadenopathy
• unexplained diarrhea
• thrush
• oral hairy leukoplakia
• severe aphthous ulcers
• severe or recurrent vaginal candidiasis

• severe forms of common skin diseases such as
  Tinea, Herpes, Zoster, seborrhea, or molluscum
• unexplained lymphopenia
• Pneumococcal bacteremia
• FUO
• other STDs
• Opportunistic Infections

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Oral Hairy Leukoplakia
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HIV Diseases Spectrum

• Mechanisms of illness in HIV-infected patients
• Directly related to HIV
• Due to HIV-induced immunosuppression
• Due to antiretroviral therapy or other therapies
• Due to co-morbid or unrelated illnesses
• Staging Systems for HIV Infection
• HIV-related diseases by clinical syndrome

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Potentially Serious and/or Life-Threatening
Toxicities with Antiretroviral Agents

• Nucleoside analogue RTIs syndrome of lactic
  acidosis and hepatic steatosis
• Zidovudine anemia, leukopenia
• Didanosine pancreatitis
• Abacavir hypersensitivity reaction
• NNRTIs skin rash/erythema multiforme
• Protease inhibitors diabetes mellitus,
  hyperlipidemia

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Spectrum of Metabolic Complications Observed in
Patients on Antiretroviral Therapy

• Type II diabetes (new onset or worsening of
  existing diabetes)
• Hyperlipidemia
• Bone changes (osteoporosis, avascular necrosis)
• Peripheral and facial lipoatrophy
• Central obesity
• Buffalo hump (dorsocervical fat pad)
• Gynecomastia
• Lipomatosis

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Adverse Events with Other Therapies Commonly used
in HIV infection

• Trimethoprim-sulfamethoxazole fever, rash
• Dapsone fever, rash
• Clarithromycin/azithromycin diarrhea
• Ganciclovir neutropenia
• Fluconazole increased LFTs
• INH, rifampin, rifabutin increased LFTs

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Drug-Drug Interactions

• Protease inhibitors, through inhibition of
  cytochrome p450 enzymes, may lead to higher
  levels of co-administered drugs
• Nevirapine and efavirenz, through induction of
  cytochrome p450 enzymes, may reduce levels of
  co-administered drugs
• A number of other drug-drug interactions are
  important some are reviewed in DHHS guidelines

www.aidsinfo.nih.gov
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Immune Reactivation Illness

• Initiation of antiretroviral therapy may lead to
  worsening or altered clinical manifestations of
  opportunistic infections
• CMV vitritis
• MAC lymphadenitis
• Flares of Hepatitis B and C
• Conversion of subclinical cryptococcosis to acute
  meningitis
• Clinical worsening of tuberculosis

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Tuberculosis Confusion and worsening of CNS
lesion on ART From Lipman, Baker, Johnson, An
Atlas of Differential Diagnosis in HIV Disease
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HIV Diseases Spectrum

• Mechanisms of illness in HIV-infected patients
• Directly related to HIV
• Due to HIV-induced immunosuppression
• Due to antiretroviral therapy or other therapies
• Due to co-morbid or unrelated illnesses
• Staging Systems for HIV Infection
• HIV-related diseases by clinical syndrome

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Common Co-Morbid Illnesses

• Tuberculosis
• Other sexually transmitted diseases including
  genital herpes and syphilis
• Viral hepatitis (A, B, and C)
• Human papillomavirus infection

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Pulmonary Tuberculosis From Lipman, Baker,
Johnson, An Atlas of Differential Diagnosis in
HIV Disease
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HIV Diseases Spectrum

• Mechanisms of illness in HIV-infected patients
• Directly related to HIV
• Due to HIV-induced immunosuppression
• Due to antiretroviral therapy or other therapies
• Due to co-morbid or unrelated illnesses
• Staging Systems for HIV Infection
• HIV-related diseases by clinical syndrome

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CDC AIDS Surveillance Case Definition
Persistent generalized lymphadenopathy
Including thrush, severe vaginal candidiasis,
cervical cancer, constitutional symptoms, OHL,
ITP, PID, neuropathy, and other
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AIDS Indicator Conditions (US CDC)

• Candidiasis of esophagus, trachea, bronchi, or
  lungs
• Cervical cancer, invasive
• Coccidioidomycosis, extra-pulmonary
• Cryptococcosis, extra-pulmonary
• Cryptosporidiosis with diarrhea gt 1 month
• CMV of any organ other than liver, spleen, or
  node

• Histoplasmosis, extra-pulmonary
• Herpes simplex with muco-cutaneous ulcer gt 1
  month
• HIV-associated dementia
• HIV-associated wasting
• Isosporiasis with diarrhea gt 1 month
• Kaposi sarcoma
• Lymphoma

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AIDS Indicator Conditions (US CDC)

• Mycobacterium avium, disseminated
• Mycobacterium tuberculosis
• Pneumocystis carinii pneumonia
• Recurrent bacterial pneumonia, (gt 2 episodes in
  12 months)

• Progressive multifocal leukoencephalopathy
• Salmonella septicemia (non-typhoidal), recurrent
• Toxoplasmosis of internal organ
• CD4 T-lymphocyte count lt 200 cells/mm3 or CD4
  lt 14

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WHO Staging System for HIV Infection and Disease
in Adults and Adolescents

• Clinical Stage I
• Asymptomatic
• Generalized lymphadenopathy
• Performance scale 1 asymptomatic, normal
  activity

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WHO Staging System for HIV Infection and Disease
in Adults and Adolescents

• Clinical Stage II
• Weight loss lt 10 of body weight
• Minor mucocutaneous manifestations (seborrheic
  dermatitis, prurigo, fungal nail infections,
  recurrent oral ulcerations, angular cheilitis)
• Herpes zoster within the last five years
• Recurrent upper respiratory tract infections
  (bacterial sinusitis)
• And/or performance scale 2 symptomatic, normal
  activity

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WHO Staging System for HIV Infection and Disease
in Adults and Adolescents

• Clinical Stage III
• Weight loss gt 10 of body weight
• Unexplained chronic diarrhea, gt 1 month
• Unexplained prolonged fever (intermittent or
  constant, gt1 month
• Oral candidiasis (thrush)
• Oral hairy leukoplakia
• Pulmonary tuberculosis
• Severe bacterial infections (pneumonia,
  pyomyositis)
• And/or performance scale 3 bedridden lt 50 of
  the day during last month

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WHO Staging System for HIV Infection and Disease
in Adults and Adolescents

• Clinical Stage IV
• HIV wasting syndrome
• Pneumocystis carinii pneumonia
• Toxoplasmosis of the brain
• Cryptosporidiosis with diarrhea gt 1 month
• Cryptococcosis, extrapulmonary
• Cytomegalovirus disease of an organ other than
  liver, spleen, or lymph node (e.g. retinitis)
• Herpes simplex virus infection, mucocutaneous ( gt
  1 month) or visceral
• Progressive Multifocal Leukoencephalopathy

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WHO Staging System for HIV Infection and Disease
in Adults and Adolescents

• Clinical Stage IV (continued)
• Any disseminated endemic mycosis
• Candidiasis of esophagus, trachea, bronchi
• Atypical mycobacteriosis, disseminated or
  pulmonary
• Non-typhoid Salmonella septicemia
• Extrapulmonary tuberculosis
• Lymphoma
• Kaposi sarcoma
• HIV encephalopathy
• And/or performance scale 4 bedridden gt50 of the
  day during last month

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HIV Diseases Spectrum

• Mechanisms of illness in HIV-infected patients
• Directly related to HIV
• Due to HIV-induced immunosuppression
• Due to antiretroviral therapy or other therapies
• Due to co-morbid or unrelated illnesses
• Staging Systems for HIV Infection
• HIV-related diseases by clinical syndrome

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Oral Manifestations of AIDS

• Herpes simplex
• Candidiasis
• Histoplasmosis
• Oral Hairy Leukoplakia
• Kaposi sarcoma
• Lymphoma

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Oral Candidiasis (Thrush) From Lipman, Baker,
Johnson, An Atlas of Differential Diagnosis in
HIV Disease
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Kaposi Sarcoma
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Cutaneous Manifestations of AIDS

• Herpes zoster
• Herpes simplex
• Molluscum contagiosum
• Folliculitis
• Cryptococcosis
• Kaposi sarcoma
• Pruritic papular dermatitis
• Seborrheic dermatitis

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Cryptococcosis of Skin From Lipman, Baker,
Johnson, An Atlas of Differential Diagnosis in
HIV Disease
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Kaposi Sarcoma of Skin From Lipman, Baker,
Johnson, An Atlas of Differential Diagnosis in
HIV Disease
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Gastrointestinal Manifestations

• Dysphagia/odynophagia Oroesophageal candidiasis,
  CMV esophagitis, Herpes esophagitis, gingivitis,
  oral ulcers
• Persistent diarrhea Cryptosporidium, Isospora,
  Shigella, Salmonella, Clostridium difficile, E.
  histolytica, Giardia, Microporidium
• Colitis Cytomegalovirus, Kaposi sarcoma, C.
  difficile
• Perianal discomfort perianal herpes, Herpes
  proctitis

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Candida Esophagitis From Lipman, Baker,
Johnson, An Atlas of Differential Diagnosis in
HIV Disease
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Perianal Herpes From Lipman, Baker, Johnson,
An Atlas of Differential Diagnosis in HIV
Disease
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Pneumonia Complicating HIV/AIDS

• Pneumocystis carinii pneumonia (PCP), bacterial
  pneumonia, and pulmonary tuberculosis are common
  opportunistic infections in HIV/AIDS
• Many other etiologies are possible including
  other bacteria, other mycobacteria, Cryptococcus,
  other fungi, Kaposi sarcoma
• When the diagnosis is unclear, the initial
  empiric therapy is typically directed at PCP and
  bacterial pneumonia

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Pneumonia Differentiating PCP and Bacterial
Pneumonia

• PCP
• diffuse infiltrates
• subacute presentation
• lower fever
• normal or low WBC
• minimal sputum production

• Bacterial
• lobar infiltrates
• acute presentation
• higher fever
• relative leukocytosis
• purulent sputum

Findings may overlap in individual cases
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Pneumocystis Pneumonia
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Pneumocystis in Respiratory Secretions From
Lipman, Baker, Johnson, An Atlas of Differential
Diagnosis in HIV Disease
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Bacterial Pneumonia
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Pneumococcus on Sputum Gram Stain
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Acute Focal Neurologic Syndrome

• Most CNS mass lesions in AIDS can be visualized
  by both CT and MRI
• CNS toxoplasmosis, primary CNS lymphoma, and
  progressive multifocal leukoencephalopathy are
  the most common causes
• Diagnosis can often be made without brain biopsy
  based on blood tests (Toxoplasma IgG), LP
  (cytology, EBV PCR, JCV PCR), and appearance on
  imaging (CT/MRI, Thallium SPECT)

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Progressive Multifocal Leukoencephalopathy From
Lipman, Baker, Johnson, An Atlas of Differential
Diagnosis in HIV Disease
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CNS Lymphoma From Lipman, Baker, Johnson, An
Atlas of Differential Diagnosis in HIV Disease
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Acute Meningitis

• Major distinction is between bacterial
  meningitis, tuberculous meningitis, and
  cryptococcal meningitis
• Immediate therapy is potentially life-saving for
  bacterial causes
• Consider mass lesions, which are quite common in
  HIV/AIDS, before LP. In some situations, it may
  be prudent to empirically treat for bacterial
  meningitis and get CT scan of head prior to LP

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Acute Visual Loss

• CMV retinitis is by far the most common cause
• This condition typically occurs only when the CD4
  count is less than 50 cells/mm3
• As this condition is progressive with permanent
  visual loss, rapid institution of treatment is
  critical
• Diagnosis is made by retinal exam by an
  experienced ophthalmologist
• Potential treatments ganciclovir,
  valganciclovir, foscarnet, cidofovir, ganciclovir
  implant

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CMV Retinitis
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Fever of Unknown Origin

• Fever on multiple occasions, for at least 3
  weeks, with cause not evident after routine
  evaluation (history, exam, CBC, chemistries,
  blood culture, and chest x-ray)
• Differential diagnosis TB, other mycobacteria,
  fungal infection, lymphoma

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27 year old male with HIV/AIDS, fever, and flank
pain. Psoas Abscess on CT Scan
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Positive AFB Smear from Psoas Abscess (culture
MTB)
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Many Patients are Asymptomatic

• Review modes of transmission
• Sexual male to female, female to male, male to
  male includes oral-genital and anal-genital
  contact
• Blood-borne injection drug use, transfusion,
  needle stick by healthcare provider
• Perinatal in-utero, during birth, breast feeding
• Assess risk through a sexual and drug use history
• Perform HIV testing

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Summary

• Mechanisms of illness in HIV include HIV itself,
  HIV-induced immunosuppression, side effects of
  treatment including immune reconstitution, and
  co-morbid illnesses
• Several classification systems exist for
  HIV-related diseases
• Although many different pathogens and processes
  cause clinical illness, there is a smaller
  differential diagnosis for specific clinical
  syndromes