80 Hematologic Manifestations of Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome

Question 1

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

Answer 1

Lentivirus

Question 2

HIV-1 actually comprises four distinct viruses

Answer 2

Types M, N, O, and P

Question 3

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

Answer 3

Group M

Question 4

The result of cross-species transmission of SIV from sooty mangabeys to humans

Answer 4

HIV-2

Question 5

HIV1 or HIV2

Progress with disease more slowly and have lower plasma viral loads (often nondetectable)

Answer 5

HIV2

Question 6

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

Answer 6

Group M

Question 7

Geographic localization of Group M

Subtypes A and D:
Subtype C:
Subtype B:
CRF01:

Answer 7

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

Question 8

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:

Answer 8

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

Question 9

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.

Answer 9

Mucosal transmission during sex

Question 10

To infect most cells, HIV must bind to CD4 and one of two major coreceptors:

Answer 10

CCR5 or CXCR4

** In most cases, CCR5-utilizing viral strains are those that are transmitted and predominate early in disease

Question 11

Replication of HIV occurs in

Answer 11

tissue macrophages and dendritic cells

Question 12

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

Answer 12

8 to 10 years

Question 13

Those who maintain CD4+ T-cell counts >500 for 5 years without therapy

Answer 13

Long-term nonprogressors

Question 14

Those with low or nondetectable plasma HIV RNA without treatment

Answer 14

Elite controllers

Question 15

Tumors classified as AIDS-defining malignancies

Answer 15

Kaposi sarcoma
Cervical cancer
Certain subtypes of non-Hodgkin lymphoma (NHL) (initially Burkitt lymphoma)
Immunoblastic lymphoma
Primary CNS lymphoma

Question 16

HIV STAGING: Infection within the previous 6 months

Answer 16

Stage 0

Question 17

HIV STAGING: CD4 count ≥500 cells/μL (or ≥26%)

Answer 17

Stage 1

Question 18

HIV STAGING: CD4 count 200–499 cells/μL
(or 14%–25%)

Answer 18

Stage 2

Question 19

HIV STAGING: AIDS-defining condition or CD4 count <200 cells/μL (or <14%)

Answer 19

Stage 3

Question 20

Opportunistic Infections by CD4 Count

> 500 cells/μL

Answer 20

Any condition that can occur in HIVuninfected
persons, eg, bacterial pneumonia, tuberculosis, varicella zoster, herpes simplex virus

Question 21

Opportunistic Infections by CD4 Count

350–499 cells/μL

Answer 21

Thrush, seborrheic dermatitis, oral hairy
leukoplakia, molluscum contagiosum

Question 22

Opportunistic Infections by CD4 Count

200–349 cells/μL

Answer 22

Kaposi sarcoma, lymphoma

Question 23

Opportunistic Infections by CD4 Count

100–199 cells/μL

Answer 23

Pneumocystis pneumonia, Candida esophagitis, cryptococcal meningitis

Question 24

Opportunistic Infections by CD4 Count

<100 cells/μL

Answer 24

Toxoplasma encephalitis, disseminated, Mycobacterium avium complex, progressive
multifocal leukoencephalopathy, cytomegalovirus retinitis, primary CNS lymphoma, microsporidia

Question 25

TRUE OR FALSE All HIV-infected persons be offered ART regardless of CD4 count

Answer 25

TRUE All HIV-infected persons be offered ART regardless of CD4 count

Question 26

Primary Prophylaxis: Pneumocystis pneumonia CD4 <200 cells/μL or <14% or oral candidiasis or an AIDS-defining illness

Answer 26

Trimethoprimsulfamethoxazole or dapsone or aerosolized pentamidine

Question 27

Primary Prophylaxis: Tuberculosis Purified protein derivative >5 mm or positive interferon-γ release assay

Answer 27

Isoniazid and pyridoxine

Question 28

Primary Prophylaxis: Toxoplasmosis Immunoglobulin G+ and CD4 <100 cells/μL

Answer 28

Trimethoprimsulfamethoxazole or dapsone plus pyrimethamine plus leucovorin

Question 29

Primary Prophylaxis: Mycobacterium avium complex CD4 <50 cells/μL

Answer 29

Azithromycin or Clarithromycin

Question 30

An acute inflammatory reaction as a result of reconstitution of the immune system in the presence of organisms or foreign antigens

Answer 30

Immune reconstitution inflammatory syndrome (IRIS)

Question 31

Risk factors for the development of IRIS

Answer 31

Low baseline CD4 count More severe disease A short interval between treatment of the opportunistic infection and initiation of ART

Question 32

Treatment of IRIS

Answer 32

Treatment of the underlying infection or condition Continued ART Antiinflammatory medication, such as glucocorticoids

Question 33

The impediment to cure for nearly all HIV-infected people

Answer 33

The persistence of replication-competent but transcriptionally silent HIV proviral DNA in long-lived resting cells (the HIV latent reservoir)

Question 34

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

Answer 34

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

Question 35

The most common malignancy in people living with HIV worldwide.

Answer 35

Kaposi sarcoma

Question 36

AIDS-Defining Malignancies and Oncogenic Viruses Kaposi sarcoma: Aggressive non-Hodgkin lymphoma: Primary CNS lymphoma: Invasive cervical cancer:

Answer 36

AIDS-Defining Malignancies and Oncogenic Viruses Kaposi sarcoma: HHV8 Aggressive non-Hodgkin lymphoma: EBV, HHV8 Primary CNS lymphoma: EBV Invasive cervical cancer: HPV

Question 37

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.

Answer 37

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.

Question 38

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

Answer 38

Myc gene on chromosome 8

Question 39

More than ______of patients with HIV-associated Burkitt lymphoma present with stage IV disease and extranodal sites are often involved.

Answer 39

More than 80%

Question 40

A common feature of CNS involvement of Burkitt lymphoma

Answer 40

Cranial nerve palsies

Question 41

TRUE OR FALSE As in the HIV-negative setting, CHOP is not adequate treatment for Burkitt lymphoma and should not be used.

Answer 41

TRUE As in the HIV-negative setting, CHOP is not adequate treatment for Burkitt lymphoma and should not be used.

Question 42

Primary CNS lymphoma in HIV-positive patients usually have a CD4 count of less than_______

Answer 42

CD4 count of less than 50 cells/μL and often of less than 20 cells/μL.

Question 43

The pathophysiology of HIV-associated primary CNS lymphoma is related to _______ virus, which is detectable in virtually all case

Answer 43

EBV

Question 44

The pathophysiology of HIV-associated primary CNS lymphoma is related to _______ virus, which is detectable in virtually all case

Answer 44

EBV

Question 45

In one series, the most common symptom of CNS lymphoma

Answer 45

Headache

Question 46

Characteristic features on magnetic resonance imaging of the brain in primary CNS lymphoma

Answer 46

A single to several mass lesions in the subcortical white matter

Question 47

Anatomic sites commonly involved are predominantly in primary CNS lymphoma

Answer 47

Cerebral cortex and periventricular area Cerebellar or brainstem involvement is rare

Question 48

TRUE OR FALSE Detection of EBV in the CSF supports, but does not confirm, the diagnosis of primary CNS lymphoma

Answer 48

TRUE Detection of EBV in the CSF supports, but does not confirm, the diagnosis of primary CNS lymphoma

Question 49

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.

Answer 49

PET-CT of the brain

Question 50

A rare and very aggressive B-cell NHL with plasmacytic differentiation that often involves the oral cavity, typically the gingiva and the palate.

Answer 50

Plasmablastic lymphoma

Question 51

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.

Answer 51

Primary effusion lymphoma (PEL)

Question 52

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.

Answer 52

Extracavitary PEL

Question 53

100% of PEL are ___________–positive and approximately 80% are EBV-positive

Answer 53

human herpesvirus-8 (HHV8)

Question 54

HHV8 plays a key pathophysiologic role, possibly by elaboration of a viral homologue of _______ and a viral homologue of ____________

Answer 54

FLICE inhibitory protein interleukin (IL)-6

Question 55

Other HHV8-related disorders

Answer 55

Castleman disease Kaposi sarcoma Aggressive NHL

Question 56

ART that causes marrow suppression and should be avoided in patients receiving myelosuppressive chemotherapy

Answer 56

Zidovudine

Question 57

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

Answer 57

Castleman disease

Question 58

The pathophysiology of Castleman disease is related to

Answer 58

IL-6

Question 59

The morphology of multicentric Castleman disease in HIV-positive patients

Answer 59

Plasmablastic cells in the mantle zone of the follicles; HHV8 is detectable in the plasmablasts

Question 60

The backbone of treatment of Castleman disease

Answer 60

Rituximab

Question 61

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

Answer 61

Siltuximab

Question 62

An anti–IL-6 receptor monoclonal antibody FDA-approved for use in rheumatoid arthritis but not for treatment of Castleman disease

Answer 62

Tocilizumab

Question 63

Most common lymphoma in patients with HIV

Answer 63

DLBCL

Question 64

A syndrome characterized by an inflammatory illness similar to a flare of Castleman disease, but without the pathologic diagnosis of Castleman disease

Answer 64

KSHV-associated inflammatory cytokine syndrome (KICS)

Question 65

Immunohistochemical and Molecular Diagnostic Findings Diffuse large-B-cell lymphoma

Answer 65

Immunohistochemical and Molecular Diagnostic Findings Diffuse large-B-cell lymphoma: CD20+, may have c-myc translocation

Question 66

Immunohistochemical and Molecular Diagnostic Findings Burkitt’s lymphoma

Answer 66

CD20+, CD10+, c-myc translocation

Question 67

Immunohistochemical and Molecular Diagnostic Findings AIDS-related primary CNS lymphoma

Answer 67

CD20+, EBV+

Question 68

Immunohistochemical and Molecular Diagnostic Findings Primary effusion lymphoma

Answer 68

DC20−, KSHV+, EBV+ (in approximately 80% of cases)

Question 69

Immunohistochemical and Molecular Diagnostic Findings Plasmablastic lymphoma

Answer 69

CD20−, EBV+, may have c-myc translocation

Question 70

Immunohistochemical and Molecular Diagnostic Findings KSHV-associated multicentric Castleman’s disease

Answer 70

KSHV+, lambda-restricted plasmablasts; a proportion of infected cells are viral IL-6+

Question 71

Immunohistochemical and Molecular Diagnostic Findings Classic Hodgkin lymphoma

Answer 71

Often EBV+, Reed-Sternberg cells

Question 72

Results from failure to regulate the immune response, resulting in excess activation of T lymphocytes, increased cytokine secretion, and hyperactivation of macrophages

Answer 72

Hemophagocytic syndrome

Question 73

An ART that can cause macrocytic anemia and leukopenia and is not commonly used at present because of its toxicity.

Answer 73

Zidovudine

Question 74

Prophylactic drug used for P. jiroveci prophylaxis, can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency

Answer 74

Dapsone or trimethoprim-sulfamethoxazole

Question 75

Drug used to treat herpes simplex virus, varicella zoster, CMV, and sometimes HHV8, often cause pancytopenia.

Answer 75

Ganciclovir or valganciclovir

Question 76

Drug for PCP prophylaxis that can also cause myelosuppression and pancytopenia

Answer 76

Trimethoprim-sulfamethoxazole

Question 77

The optimal treatment for HIV-associated anemia

Answer 77

Initiation of ART

Question 78

An FDA-approved indication for erythropoietin in HIV patients

Answer 78

Anemia caused by zidovudine and an erythropoietin level of 500 mU/mL or less

Question 79

The primary treatment of HIV-associated ITP

Answer 79

Initiation of ART ## Footnote ART typically takes **3 months** to improve the platelet counts

Question 80

Treatment option in HIV-associated ITP with severe thrombocytopenia, Rh+ and has an intact spleen

Answer 80

IV anti-D

Question 81

Major side effect of anti-D treatment

Answer 81

Drop in the hemoglobin (significant hemolysis)

Question 82

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.

Answer 82

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.