80 Hematologic Manifestations of Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome Flashcards
HIV-1, the virus that causes AIDS, is a ___________ that originated as a simian immunodeficiency virus (SIV) in chimpanzees and entered the human population in the early 20th century in equatorial Africa
Lentivirus
HIV-1 actually comprises four distinct viruses
Types M, N, O, and P
The viral type responsible for the HIV-1 pandemic, was detected in a tissue sample from 1959 and probably entered the human population in or around Kinshasa, Democratic Republic of Congo (then Leopoldville, Belgium Congo) between 1910 and 1930
Group M
The result of cross-species transmission of SIV from sooty mangabeys to humans
HIV-2
HIV1 or HIV2
Progress with disease more slowly and have lower plasma viral loads (often nondetectable)
HIV2
The globally predominant viral strain and is further divided into nine subtypes and many more recombinant viruses (circulating recombinant forms [CRFs]) with some geographic localization
Group M
Geographic localization of Group M
Subtypes A and D:
Subtype C:
Subtype B:
CRF01:
Geographic localization of Group M
Subtypes A and D: East Africa
Subtype C: most prevalent subtype globally, in South Africa, India, and Asia
Subtype B: Caribbean, the Americas, and Western Europe
CRF01:Southeast Asia
Predominant mode of transmission in the following areas:
United States, Northern Europe, Australia, and parts of Central and South America:
Sub-Saharan Africa:
Southern and Eastern Europe and Southeast Asia:
Predominant mode of transmission in the following areas:
United States, Northern Europe, Australia, and parts of Central and South America: sexual contact between men
Sub-Saharan Africa: heterosexual spread
Southern and Eastern Europe and Southeast Asia:injection drug use followed by sexual transmission
Eighty percent of HIV infections occur via ____________________when cell-free and cell-associated virions transverse the epithelium to gain access to macrophages, Langerhans cells, dendritic cells, and CD4-expressing T lymphocytes.
Mucosal transmission during sex
To infect most cells, HIV must bind to CD4 and one of two major coreceptors:
CCR5 or CXCR4
** In most cases, CCR5-utilizing viral strains are those that are transmitted and predominate early in disease
Replication of HIV occurs in
tissue macrophages and dendritic cells
Typically, the asymptomatic phase of chronic infection will last for ________, although there is great interindividual variation dictated by the effectiveness of the immune response in controlling HIV replication
8 to 10 years
Those who maintain CD4+ T-cell counts >500 for 5 years without therapy
Long-term nonprogressors
Those with low or nondetectable plasma HIV RNA without treatment
Elite controllers
Tumors classified as AIDS-defining malignancies
Kaposi sarcoma
Cervical cancer
Certain subtypes of non-Hodgkin lymphoma (NHL) (initially Burkitt lymphoma)
Immunoblastic lymphoma
Primary CNS lymphoma
HIV STAGING: Infection within the previous 6 months
Stage 0
HIV STAGING: CD4 count ≥500 cells/μL (or ≥26%)
Stage 1
HIV STAGING: CD4 count 200–499 cells/μL
(or 14%–25%)
Stage 2
HIV STAGING: AIDS-defining condition or CD4 count <200 cells/μL (or <14%)
Stage 3
Opportunistic Infections by CD4 Count
> 500 cells/μL
Any condition that can occur in HIVuninfected
persons, eg, bacterial pneumonia, tuberculosis, varicella zoster, herpes simplex virus
Opportunistic Infections by CD4 Count
350–499 cells/μL
Thrush, seborrheic dermatitis, oral hairy
leukoplakia, molluscum contagiosum
Opportunistic Infections by CD4 Count
200–349 cells/μL
Kaposi sarcoma, lymphoma
Opportunistic Infections by CD4 Count
100–199 cells/μL
Pneumocystis pneumonia, Candida esophagitis, cryptococcal meningitis
Opportunistic Infections by CD4 Count
<100 cells/μL
Toxoplasma encephalitis, disseminated, Mycobacterium avium complex, progressive
multifocal leukoencephalopathy, cytomegalovirus retinitis, primary CNS lymphoma, microsporidia
TRUE OR FALSE
All HIV-infected persons be offered ART regardless of CD4 count
TRUE
All HIV-infected persons be offered ART regardless of CD4 count
Primary Prophylaxis: Pneumocystis pneumonia
CD4 <200 cells/μL or <14% or oral candidiasis or an AIDS-defining illness
Trimethoprimsulfamethoxazole or dapsone or
aerosolized pentamidine
Primary Prophylaxis: Tuberculosis
Purified protein derivative >5 mm or positive
interferon-γ release assay
Isoniazid and pyridoxine
Primary Prophylaxis: Toxoplasmosis
Immunoglobulin G+ and CD4 <100 cells/μL
Trimethoprimsulfamethoxazole or dapsone plus pyrimethamine plus leucovorin
Primary Prophylaxis: Mycobacterium avium complex
CD4 <50 cells/μL
Azithromycin or Clarithromycin
An acute inflammatory reaction as a result of reconstitution of the immune system in the presence of organisms or foreign antigens
Immune reconstitution inflammatory syndrome (IRIS)
Risk factors for the development of IRIS
Low baseline CD4 count
More severe disease
A short interval between treatment of the opportunistic infection and initiation of ART
Treatment of IRIS
Treatment of the underlying infection or condition
Continued ART
Antiinflammatory medication, such as glucocorticoids
The impediment to cure for nearly all HIV-infected people
The persistence of replication-competent but transcriptionally silent HIV proviral DNA in long-lived resting cells (the HIV latent reservoir)
TRUE OR FALSE
All patients who present to the hematologist with NHL, Hodgkin lymphoma, idiopathic thrombocytopenic purpura (ITP), or other malignancies should be tested for HIV
TRUE
All patients who present to the hematologist with NHL, Hodgkin lymphoma, idiopathic thrombocytopenic purpura (ITP), or other malignancies should be tested for HIV
**5% of those with diffuse large B-cell lymphoma (DLBCL) and 22% of patients with Burkitt lymphoma in the United States are HIV-positive
The most common malignancy in people living with HIV worldwide.
Kaposi sarcoma
AIDS-Defining Malignancies and Oncogenic Viruses
Kaposi sarcoma:
Aggressive non-Hodgkin lymphoma:
Primary CNS lymphoma:
Invasive cervical cancer:
AIDS-Defining Malignancies and Oncogenic Viruses
Kaposi sarcoma: HHV8
Aggressive non-Hodgkin lymphoma: EBV, HHV8
Primary CNS lymphoma: EBV
Invasive cervical cancer: HPV
TRUE OR FALSE
HIV-associated Burkitt lymphoma is approximately one-third as common as HIV-associated DLBCL in the Western world, and occurs at a lower CD4 count.
FALSE
HIV-associated Burkitt lymphoma is approximately one-third as common as HIV-associated DLBCL in the Western world, and occurs at a HIGHER CD4 count.
Burkitt lymphoma in HIV-negative people, and involves translocation of the _____________ with one of the immunoglobulin (Ig) genes on chromosomes 2, 14, or 22, resulting in overexpression of Myc
Myc gene on chromosome 8
More than ______of patients with HIV-associated Burkitt lymphoma present with stage IV disease and extranodal sites are often involved.
More than 80%
A common feature of CNS involvement of Burkitt lymphoma
Cranial nerve palsies
TRUE OR FALSE
As in the HIV-negative setting, CHOP is not adequate treatment for Burkitt lymphoma and should not be used.
TRUE
As in the HIV-negative setting, CHOP is not adequate treatment for Burkitt lymphoma and should not be used.
Primary CNS lymphoma in HIV-positive patients usually have a CD4 count of less than_______
CD4 count of less than 50 cells/μL and often of less than 20 cells/μL.
The pathophysiology of HIV-associated primary CNS lymphoma is related to _______ virus, which is detectable in virtually all case
EBV
The pathophysiology of HIV-associated primary CNS lymphoma is related to _______ virus, which is detectable in virtually all case
EBV
In one series, the most common symptom of CNS lymphoma
Headache
Characteristic features on magnetic resonance imaging of the brain in primary CNS lymphoma
A single to several mass lesions in the subcortical white matter
Anatomic sites commonly involved are predominantly in primary CNS lymphoma
Cerebral cortex and periventricular area
Cerebellar or brainstem involvement is rare
TRUE OR FALSE
Detection of EBV in the CSF supports, but does not confirm, the diagnosis of primary CNS lymphoma
TRUE
Detection of EBV in the CSF supports, but does not confirm, the diagnosis of primary CNS lymphoma
Can help distinguish primary CNS lymphoma from other common causes of focal brain lesions in profoundly immunosuppressed patients with HIV, namely, cerebral toxoplasmosis and other infections.
PET-CT of the brain
A rare and very aggressive B-cell NHL with plasmacytic differentiation that often involves the oral cavity, typically the gingiva and the palate.
Plasmablastic lymphoma
An aggressive B-cell lymphoma characterized by lymphomatous effusions in body cavities, most commonly pleural effusion, followed by ascites and pericardial effusion or multiple body cavities; lymph nodes, marrow, and skin can also be involved.
Primary effusion lymphoma (PEL)
A solid variant of PEL that presents without effusion, but with lymph node, gastrointestinal, skin, or liver involvement and shares epidemiologic and immunophenotypic characteristics with the classical PEL.
Extracavitary PEL
100% of PEL are ___________–positive and approximately 80% are EBV-positive
human herpesvirus-8 (HHV8)
HHV8 plays a key pathophysiologic role, possibly by elaboration of a viral homologue of _______ and a viral homologue of ____________
FLICE inhibitory protein
interleukin (IL)-6
Other HHV8-related disorders
Castleman disease
Kaposi sarcoma
Aggressive NHL
ART that causes marrow suppression and should be avoided in patients receiving myelosuppressive chemotherapy
Zidovudine
A rare polyclonal lymphoproliferative disorder characterized by periodic flares (an inflammatory illness accompanied by lymphadenopathy and splenomegaly), and a high risk of progression to lymphoma
Castleman disease
The pathophysiology of Castleman disease is related to
IL-6
The morphology of multicentric Castleman disease in HIV-positive patients
Plasmablastic cells in the mantle zone of the follicles; HHV8 is detectable in the plasmablasts
The backbone of treatment of Castleman disease
Rituximab
An anti–IL-6 monoclonal antibody approved by the FDA for treatment of Castleman disease in HIV-negative patients but not in HIV-positive patients
Siltuximab
An anti–IL-6 receptor monoclonal antibody FDA-approved for use in rheumatoid arthritis but not for treatment of Castleman disease
Tocilizumab
Most common lymphoma in patients with HIV
DLBCL
A syndrome characterized by an inflammatory illness similar to a flare of Castleman disease, but without the pathologic diagnosis of Castleman disease
KSHV-associated inflammatory cytokine syndrome (KICS)
Immunohistochemical and Molecular Diagnostic Findings
Diffuse large-B-cell lymphoma
Immunohistochemical and Molecular Diagnostic Findings
Diffuse large-B-cell lymphoma: CD20+, may have c-myc translocation
Immunohistochemical and Molecular Diagnostic Findings
Burkitt’s lymphoma
CD20+, CD10+, c-myc translocation
Immunohistochemical and Molecular Diagnostic Findings
AIDS-related primary CNS lymphoma
CD20+, EBV+
Immunohistochemical and Molecular Diagnostic Findings
Primary effusion lymphoma
DC20−, KSHV+, EBV+ (in approximately 80% of cases)
Immunohistochemical and Molecular Diagnostic Findings
Plasmablastic lymphoma
CD20−, EBV+, may have c-myc translocation
Immunohistochemical and Molecular Diagnostic Findings
KSHV-associated multicentric Castleman’s disease
KSHV+, lambda-restricted plasmablasts; a proportion of infected cells are viral IL-6+
Immunohistochemical and Molecular Diagnostic Findings
Classic Hodgkin lymphoma
Often EBV+, Reed-Sternberg cells
Results from failure to regulate the immune response, resulting in excess activation of T lymphocytes, increased cytokine secretion, and hyperactivation of macrophages
Hemophagocytic syndrome
An ART that can cause macrocytic anemia and leukopenia and is not commonly used at present because of its toxicity.
Zidovudine
Prophylactic drug used for P. jiroveci prophylaxis, can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency
Dapsone or trimethoprim-sulfamethoxazole
Drug used to treat herpes simplex virus, varicella zoster, CMV, and sometimes HHV8, often cause pancytopenia.
Ganciclovir or valganciclovir
Drug for PCP prophylaxis that can also cause myelosuppression and pancytopenia
Trimethoprim-sulfamethoxazole
The optimal treatment for HIV-associated anemia
Initiation of ART
An FDA-approved indication for erythropoietin in HIV patients
Anemia caused by zidovudine and an erythropoietin level of 500 mU/mL or less
The primary treatment of HIV-associated ITP
Initiation of ART
ART typically takes 3 months to improve the platelet counts
Treatment option in HIV-associated ITP with severe thrombocytopenia, Rh+ and has an intact spleen
IV anti-D
Major side effect of anti-D treatment
Drop in the hemoglobin (significant hemolysis)
TRUE OR FALSE
In HIV-associated ITP, glucocorticoids are less attractive because of the potential to decrease CD4 counts, increase the risk of infection, and increase the risk of Kaposi sarcoma progression.
TRUE
In HIV-associated ITP, glucocorticoids are less attractive because of the potential to decrease CD4 counts, increase the risk of infection, and increase the risk of Kaposi sarcoma progression.
