The document discusses HIV and AIDS. It provides information on: - The structure and life cycle of HIV. - How HIV infects and destroys CD4+ T cells, leading to immunosuppression and susceptibility to opportunistic infections. - The typical stages of untreated HIV infection from acute infection to AIDS, defined as a CD4 count below 200 or an AIDS-defining condition. - Common opportunistic infections and cancers seen in AIDS patients due to severe immune deficiency.

1. Prepared and presented by
Marc Imhotep Cray, M.D.

2. Marc Imhotep Cray, M.D. 2
HIV and AIDS
Textbook of AIDS Pathology_Introduction
HIV Infection & Antiretroviral Agents
HIV/AIDS Patient Animations
HIV Science-Antiviral Drugs Animations
Glossary HIV Related Terms_PDF Download

3. Marc Imhotep Cray, M.D.
Clinical Case: Make the Diagnosis
3
 A 40-year-old male was seen by his internist with chief
complaints of fever, night sweats, increased episodes of
diarrhea during the past month, and a 30-pound weight
loss over the previous 4 months. On physical exam, he
had oral thrush and cervical lymphadenopathy.
Laboratory findings were significant for a CD4+ cell
count of 100 cells/uL.

4. Marc Imhotep Cray, M.D.
Acquired immunodeficiency syndrome
(AIDS) Capsule
AIDS is an infectious disease caused by human HIV
AIDS is characterized by a profound suppression of immune
system and susceptibility to opportunistic infections,
neurologic disorders, and malignancies
4
Symptomatic phase and AIDS is end-stage HIV disease
 Opportunistic protozoal, fungal, bacterial, & viral infections, Malignancies, Neurological
disorders Other systems are also affected, including CV, Pulm, GI
 AIDS is Dx for a person who is HIV-positive and has a T-cell count below 200 cells/ uL (or
200/ mm3) or presents with one of AIDS defining opportunistic infections /malignancies
 AIDS is characterized by a CD4+ T lymphocyte count below 200 cells/mm3 (normal = 800–
1200/mm3)

5. Marc Imhotep Cray, M.D.
AIDS Capsule cont.
5
Two genetically different, but closely related forms of human
pathogens are recognized: HIV-1 and HIV-2
 Both are RNA viruses belonging to retrovirus family (lentivirus genus)
 HIV expresses cell surface protein gp120, which binds to CD4+
surface molecule of T helper lymphocytes
 Proviral DNA synthesized by a reverse transcription in infected
cells is integrated into host’s nuclear DNA
Main characteristics of HIV

6. Marc Imhotep Cray, M.D.
Acquired Immune Deficiency Syndrome (AIDS)
 Infection with HIV causes a continuum of diseases, from acute (primary)
HIV infection  prolonged periods of asymptomatic infection  full
blown AIDS
 Diagnosis of AIDS implies there has been significant damage to immune
system and is a surveillance case definition established by Centers for
Disease Control and Prevention (CDC) as part of classification of clinical
status of HIV-infected patients
 To date, two types of HIV, HIV-1 and HIV-2, have been identified as
causative agents of AIDS
 There are several subtypes (clades) of HIV-1 with varying distributions throughout
world, whereas HIV-2 is more prevalent in Western Africa
Important Epidemiology Note: “The Pandemic of HIV continues to be a serious international problem
As of 2005, there were about 38.6 million people worldwide living with HIV/AIDS, with 2.8 million
deaths in 2005 and 4 million people newly infected with HIV.”
U.S. CDC (Centers for Disease Control and Prevention). HIV Surveillance Report Infographic / Full Report (2018).
6

7. Marc Imhotep Cray, M.D.
Human Immunodeficiency Virus
Etiology and Epidemiology: HIV-1 causes AIDS
Transmission
 Unprotected sexual intercourse
o Homosexual contact is major mode of HIV-1 transmission in
United States
o Heterosexual transmission is most common in rest of world
 Shared contaminated needles (IVDAs)
 Contaminated blood transfusions
 Vertical transmission from mother to child virus
crosses placenta and is transmitted through breast milk
7

8. Marc Imhotep Cray, M.D.
Prevalence of human immunodeficiency virus (HIV)
infection among the adult population worldwide.
8World Health Organization (WHO) figures from 2006 demonstrate extent of HIV pandemic throughout world.

9. Marc Imhotep Cray, M.D.
HIV Structure (simplified)
Ireland KA. Visualizing Human Biology, 3rd ed. New Jersey: Wiley & Sons, 2011.
9

10. HIV genes, gene products & structure of HIV-1 virion
Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed. 2014.
Modified from: Hammer GD and McPhee JS, Eds. Pathophysiology
of Disease : An Introduction to Clinical Medicine, 7th Ed. 2014
HIV is a group of related retroviruses, whose
RNA encodes for nine genes

11. 11
Life Cycle of HIV
Robbins Basic Pathology 10e, Elsevier, 2018. Fig. 4.19, Pg. 176.

12. 12
HIV Reproduction/ infection
process
Modified from: Ireland KA. Visualizing Human
Biology, 3rd ed. New Jersey: Wiley & Sons, 2011
1. Virus attaches to host cell at CD4 receptor
2. Viral RNA is injected into cell and using reverse
transcriptase makes a complementary DNA strand
(cDNA)
3. Viral cDNA makes a second strand of DNA
double-stranded viral DNA enters nucleus and is
inserted into host DNA where it can remain
dormant for many years as a provirus
4. Viral cDNA is transcribed into viral RNA and
exported into cytoplasm
5. Viral RNA is translated into new viral particles
6. Assembled virus buds from cell membrane and is
released
Helper T-
Lymphocyte
(CD4+ Cell)

13. Marc Imhotep Cray, M.D.
Human immunodeficiency virus-1 (HIV-1) seen
budding from infected cells (arrows)
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 2012
13

14. HIV-1 pathogenesis
 HIV-1 attaches via envelope glycoprotein gp120 to CD4
molecule and a second coreceptor (chemokine receptor)
on helper T lymphocytes, monocytes-macrophages, and
mucosal dendritic cells
 HIV-1 may infect both activated and nonactivated CD4+
cells in draining lymph node
 Virus remains latent in nonactivated (resting) T cells but
replicates in and kills T cells activated by infection or
cytokines or both
Note: chemokine=any of a family of low molecular weight
(8–10 kD) cytokines that induce chemotaxis or chemokinesis
in leukocytes (or in particular populations of leukocytes).
Robbins Basic Pathology 10e, Elsevier, 2018. Fig. 4.19, Pg. 178.

15. Marc Imhotep Cray, M.D.
HIV /AIDS pathogenesis
15
AIDS is consequence of infection w HIV-1 which infects
multiple cell lines, including lymphocytes, monocytes,
macrophages, and dendritic cells
 With HIV infection, there is an absolute reduction of CD4 T
lymphocytes, an accompanying deficit in CD4+ T-lymphocyte
function and an associated increase in CD8+ cytotoxic T
lymphocytes (CTLs)
 “Reversal of the CD4/CD8 Ratio”
A normal CD4/CD8 ratio is 2.0, with CD4 lymphocytes equal to or greater than
400/mm3 and CD8 lymphocytes equal to 200 to 800/mm3. If the ratio is higher
than 2, it means the immune system is strong and HIV unlikely. If the ratio is less
than 1, pt. may have HIV

16. Marc Imhotep Cray, M.D.
HIV AIDS pathogenesis cont.
16
 In addition to cell-mediated immune defects (T
lymphocytes ) B-lymphocyte function (humoral-
mediated immunity) is altered  such that many infected
individuals have marked hypergammaglobulinemia but
impaired specific antibody responses
Resultant immunosuppression predisposes patients to
constellation of opportunistic infections that
characterizes AIDS

17. Marc Imhotep Cray, M.D.
Human Immunodeficiency Virus
17
Clinical Manifestations: HIV disease is
characterized by
 an acute phase with a “flu-like” or infectious
mononucleosis-like syndrome, followed by
 an asymptomatic phase of clinical latency
characterized by fatigue, weight loss, night sweats, or
lymphadenopathy with a median time of 7-10 years to
development of AIDS

18. Marc Imhotep Cray, M.D.
Human Immunodeficiency Virus
18
Symptomatic phase and AIDS is end-stage disease
 AIDS is characterized by a CD4+ T lymphocyte count below
200 cells/mL3 (normal = 800–1200/mL3)
 Opportunistic protozoal, fungal, bacterial, & viral infections
 Malignancies
 Neurological disorders

19. Marc Imhotep Cray, M.D.
HIV W/U
 Diagnostic Test:
 Bloods: CBC, Lytes, LFTs, lipids, glucose, lymphocyte subsets
 HIV specific:
o Enzyme-linked immunosorbent assay (ELISA)
o Western blot test
o Immunofluorescence assay (IFA)
o Nucleic acid testing
 Virology screen: HIV antibody, HIV viral load, HIV
genotype, hepatitis serology, cytomegalovirus (CMV)
antibody, syphilis screen
 Other infection, e.g. tuberculosis if indicated
19

20. Marc Imhotep Cray, M.D.
Runge MS and Greganti MA. Netter's Internal Medicine 2nd Ed. Saunders, 2008
20
STI and HIV Lab Testing:

21. Marc Imhotep Cray, M.D.
Natural History (NH) & Phases of HIV infection
1. Early, acute phase: Self-limited acute illness 3 to 6 weeks after
infection
 High level of virus production and widespread infection of lymphoid
organs
2. Middle, chronic phase: No symptoms or persistent lymphadenopathy
for several years
3. Minor infections
4. Final, crisis: Long-lasting fever, severe opportunistic infections,
secondary neoplasms, and neurologic disorders
 This usually develops after 7 to 10 years of chronic phase
Four major stages of HIV infection:
21

22. Marc Imhotep Cray, M.D.
Four major stages of HIV infection cont.
22
1) With acute HIV infection, individual may remain asymptomatic
or develop an acute illness that resembles influenza or
infectious mononucleosis Sx usually develop within 2 to 6
weeks after infection
 During this stage, antibodies to HIV are generally undetectable
2) Seroconversion usually occurs during clinical latency, an
asymptomatic period that would last approx. 7 to 10 years in an
untreated patient
 Low-level (but persistent) replication of HIV causes a gradual decrease
in CD4+ T cells, and minor opportunistic infections may occur

23. Marc Imhotep Cray, M.D.
Four major stages of HIV infection cont.
23
3) During crisis phase, escalation of viral replication
leads to a more rapid T-cell decline
 clinically apparent as weight loss, fever, fatigue, and
lymphadenopathy
4) Acquired immunodeficiency syndrome (AIDS) is
diagnosis for a person who is HIV-positive and has a T-
cell count below 200 cells/ uL ( or 200/ mm3) or
presents with one of AIDS defining opportunistic
infections /malignancies

24. Marc Imhotep Cray, M.D.
NH: Typical course of HIV
infection (1)
Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of
Disease 8th ed. Philadelphia: Saunders, 2014
Acute HIV infection may present
as a self-limited, febrile viral
syndrome characterized by:
 fatigue
 pharyngitis
 myalgias
 maculopapular rash
 lymphadenopathy and
 significant viremia
 without detectable anti-HIV
antibodies
24

25. Marc Imhotep Cray, M.D.
NH: Typical course of HIV infection (2)
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 2012
25

26. NH: Typical course of untreated HIV infection (3)
 During early period after primary
infection, there is widespread
dissemination of virus and a sharp
decrease in number of CD4 T cells in
peripheral blood
 An immune response to HIV ensues, with a
decrease in detectable viremia followed by
a prolonged period of clinical latency
• Sensitive assays for viral RNA show that virus
is present in plasma at all times
 CD4 T-cell count continues to decrease
during following years until it reaches a
critical level below which there is a
substantial risk of opportunistic diseases
26
Fauci AS, Lane HC: Human immunodeficiency virus disease: AIDS and related
disorders. In Longo DL, Fauci AS, Kasper DL, et al (editors). Harrison’s
Principles of Internal Medicine, 18th ed. McGraw-Hill, 2012.

27. 27
HIV/AIDS
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri:
Saunders-Elsevier, 2013.
Common Agents of Infection In Patients with AIDS
As indicated above,
 AIDS is characterized by a
profound suppression of
immune system and
susceptibility to
o infections
o neurologic disorders &
o malignancies

28. HIV/AIDS
Consequences & Complications
 Increased risk of opportunistic infections:
o Toxoplasmosis
o CMV, e.g. retinitis
o Pneumocystis jiroveci pneumonia
o Cryptococcal meningitis
o Mycobacterium avium complex
o Candida
o Aspergillosis
 Increased risk of malignancies:
o Kaposi’s sarcoma
o Non-Hodgkin’s lymphoma
o Cervical cancer
o Anal cancer
28

29. Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic
Foundations of Medicine, 2012
 HIV-1 mediated destruction of
cellular immune system results in
 AIDS
 Infectious and neoplastic
complications of AIDS can affect
practically every organ system
Consequences of HIV
infection and AIDS

30. HIV-AIDS Revised Surveillance Case Definition, 2014.*
 Candidiasis of bronchi, trachea, lungs, or esophagus
 Cervical cancer, invasive
 Coccidioidomycosis, disseminated or
extrapulmonary
 Cryptococcosis, extrapulmonary
 Cryptosporidiosis, chronic intestinal (>1 month
duration)
 Cytomegalovirus disease (other than liver, spleen, or
nodes; including cytomegalovirus retinitis with loss
of vision)
 Encephalopathy, HIV related
 Herpes simplex: chronic ulcers (>1 month duration)
or bronchitis, pneumonitis, or esophagitis
 Histoplasmosis, disseminated or extrapulmonary
 Isosporiasis, chronic intestinal (>1 month duration)
 Kaposi’s sarcoma
 Leukoencephalopathy, progressive multifocal
 Lymphoma, Burkitt’s (or equivalent form),
 immunoblastic (or equivalent form), or primary
of brain
 Mycobacterium avium complex or M. kansasii,
 disseminated or extrapulmonary
 Mycobacterium tuberculosis, pulmonary or
 extrapulmonary
 Mycobacterium, other species or unidentified
species,
 disseminated or extrapulmonary
 Pneumocystis carinii
 Pneumonia, recurrent
 Salmonella septicemia, recurrent
 Toxoplasmosis of brain
 Wasting syndrome due to HIV
*Patients infected with HIV and who have a CD4+ T-cell count <200 or CD4+ percent <14% are classified as having AIDS.
HIV-AIDS Revised Surveillance Case Definition, 2014.
30

31. Pneumocystis jiroveci (carinii).
HIV-associated Kaposi sarcoma in nodular stage.
HIV-associated Kaposi sarcoma in macular stage.
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013.
31

32. Marc Imhotep Cray, M.D.
HIV/AIDS
Clinical Manifestations
 HIV affects all body systems, particularly integumentary,
pulmonary, gastrointestinal (GI), neurologic, and ocular
systems
 GI manifestations develop in nearly all persons with
HIV b/c of major effect of HIV infection on GI system
 Pulmonary and cutaneous symptoms develop in ~
50% to 75% of all persons with HIV, and
 Neurologic Sx develop in 50% to 60%
32

33. Marc Imhotep Cray, M.D.
HIV/AIDS
One of most significant systemic symptoms is
malnutrition or wasting syndrome
 In Africa, HIV is known as “slim disease” b/c of
wasting
Malnutrition is defined as unintended, involuntary loss
of greater than 10% body weight
Systemic symptoms attributable to HIV infection
malnutrition include major muscle wasting, weight loss,
and loss of vitamins, minerals, and other nutrients 33

34. Marc Imhotep Cray, M.D.
Wasting syndrome cont.
34
HIV malnutrition is result of a combination of factors,
including
 an elevated metabolic rate with increased resting
energy expenditure (REE)
 chronic inflammation
 malabsorption
 anorexia
 decreased intake of food, and
 effect of multiple opportunistic insults

35. Marc Imhotep Cray, M.D.
 LYMPHOPENIA
 Predominantly caused by selective loss of CD4+ helper T-cell subset
DECREASED T-CELL FUNCTION IN VIVO
 Preferential loss of activated and memory T cells
 ↓ delayed-type hypersensitivity
 Susceptibility to opportunistic infections
 Susceptibility to neoplasms
ALTERED T-CELL FUNCTION IN VITRO
 ↓ proliferative response to mitogens, alloantigens, and soluble antigens
 ↓ cytotoxicity
 ↓ helper function for B-cell antibody production
 ↓ IL-2 and IFN-γ production
 ↓ capacity to present antigen to T cells
Major Abnormalities of Immune Function in AIDS
35

36. Marc Imhotep Cray, M.D.
Major Abnormalities of Immune Function in AIDS
cont.
 POLYCLONAL B-CELL ACTIVATION
 Hypergammaglobulinemia and circulating immune complexes
 Inability to mount de novo antibody response to new antigens
 Poor responses to normal B-cell activation signals in vitro
ALTERED MONOCYTE OR MACROPHAGE FUNCTIONS
 ↓ chemotaxis and phagocytosis
 ↓ class II HLA expression
36

37. Marc Imhotep Cray, M.D.
Most important determinants of progression
of HIV infection
CD4+ T-cell count indicates damage that has occurred to immune
system, and how close patient is to progressing to AIDS
 A high count is ideal
 Normal count ranges from 500 to 1500 cells/mm3 (500 to 1500/ mm3)
Viral load is an indication of pace at which damage is occurring
 A low viral load is ideal
 Viral load serves as a marker for disease progression and drug therapy
effectiveness by measuring amount of actively dividing HIV virus
 CD4 count better for disease staging
 Viral load better proxy for disease progression or
monitoring response to therapy
37

38. 38
How is clinically suspected diagnosis of AIDS confirmed
 Laboratory tests are performed to detect
antibodies against HIV proteins
 Seroconversion (presence of antibodies
against HIV in a previously nonreactive
individual) usually occurs within 6 months
of exposure to HIV
 Detection of infection during serologic
window before seroconversion requires
detection of viral antigens or viral RNA The diagnosis of symptomatic acute antiretroviral
syndrome during the window period with antigen-
antibody testing and HIV viral load
https://www.sciencedirect.com/science/article/pii/S2
214250918300982?via%3Dihub#sec0005

39. Marc Imhotep Cray, M.D.
Common opportunistic infections in AIDS
Opportunistic infections account for vast majority of deaths in
patients
These infections include:
 P. jiroveci pneumonia
 C. albicans infections of the mouth, esophagus, vagina, and
lungs
 Cytomegalovirus enteritis and pneumonitis
 Atypical mycobacterial infection (M. avium-intracellulare) of
GIT
 Cryptococcus neoformans meningitis
 Cryptosporidium enteritis
39

40. Marc Imhotep Cray, M.D.
Most common neoplasms associated with
HIV infections and AIDS
 Kaposi sarcoma
 Non-Hodgkin lymphoma
 Carcinoma of uterine cervix
 Squamous cell carcinoma of skin
40

41. Marc Imhotep Cray, M.D.
Neurologic consequences of HIV infection
and AIDS
Involvement of central nervous system is common (clinically
40%–60%) and may present in several forms:
HIV-related diseases
 Aseptic meningitis
 AIDS dementia complex
Opportunistic infections:
 viral (cytomegalovirus and herpes simplex virus)
 fungal(Coccidioides and Cryptococcus), and protozoal
(Toxoplasma gondii)
Neoplasms (lymphoma)
41

42. Marc Imhotep Cray, M.D.
What is “PCP pneumonia”
 PCP refers to Pneumocystis carinii pneumonia (the preferred
name is now Pneumocystis jirovecii pneumonia)
 P. jirovecii pneumonia is most common significant opportunistic
infection in HIV patients
o yeast-like fungus originally classified as protozoan and now classified
as a fungus
 typically occurs in patients with a CD4+ count of below 200
 Pneumocystis jirovecii causes a diffuse interstitial pneumonia
42

43. Marc Imhotep Cray, M.D.
PCP (2)
 Transmission: Inhaled
 Most infections are asymptomatic
 Immunosuppression (e.g., AIDS) predisposes to disease
 Clin. Findings:
 Patients typically present with fever, nonproductive cough, and
dyspnea
 Radiographic studies show bilateral diffuse infiltrates, most
pronounced in perihilar regions
o Diffuse, bilateral ground-glass opacities on CXR/CT
 Diagnosed by lung biopsy or lavage Disc-shaped yeast forms on
methenamine silver stain of lung tissue
 Patients with CD4+ counts below 200/mm3 should be started on TMP-
SMX prophylaxis
43

44. Question
A 23-year-old man presents to the emergency
department with symptoms of malaise, dry cough, and
dyspnea for several weeks. Physical examination reveals
tachypnea, tachycardia, and fever, with crackles on
auscultation. On further questioning, the patient admits
to IV drug abuse. The chest x-ray findings (top) prompt
the clinician to order a chest CT study, from which is a
representative section in the coronal plane is shown in
the bottom figure.
What is the most likely diagnosis?
A. Pneumocystis pneumonia (PCP)
B. Pneumococcal pneumonia
C. Miliary tuberculosis (TB)
D. Cytomegalovirus (CMV) pneumonia
E. Pulmonary edema
Studdiford, JS and Tully AS. USMLE Images for the Boards:
Philadelphia. Saunders,2013 44

45. 45
Studdiford, JS and Tully AS. USMLE Images for the Boards:
Philadelphia. Saunders,2013
ANSWER: Pneumocystis pneumonia (PCP)
 The Chest x-ray and Chest CT show a diffuse
ground-glass pattern throughout the lungs. The term
ground-glass refers to the edge of a microscope slide
that can be written on with pencil, and it means that
although the area remains transparent, one cannot
see detail through it This pattern is characteristic
of pneumocystis pneumonia, commonly known as
PCP
 The patient tested positive for HIV infection, likely
acquired through the sharing of contaminated
needles, and he is severely immunosuppressed.
 Sputum obtained during bronchoalveolar lavage was
positive for PCP.

46. Marc Imhotep Cray, M.D.
Other opportunistic pathogens and
malignancies: Major cause of death in AIDS
Common opportunistic infections at notable CD4+ counts:
 Toxoplasma encephalitis at <100
 Cryptococcal meningitis at <100
 Mycobacterium avium complex at <50
 Cytomegalovirus retinitis at <50
o CMV retinitis is treated with ganciclovir, a competitive
guanosine analog
• In event that ganciclovir fails foscarnet (viral DNA
polymerase inhibitor) is used
46

47. Marc Imhotep Cray, M.D.
Select HIV Infection and AIDS
Gross and Microscopic
Pathology Plates and Radiographs
47

48. Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Pneumocystis pneumonia,
microscopic
 Granular pink alveolar exudate ( ) of
Pneumocystis jiroveci pneumonia (left
panel) consists of edema fluid,
protein, Pneumocystis organisms, and
dead inflammatory cells
 Mononuclear cells infiltrate
interstitium
 Gomori methenamine silver (GMS)
stain on bronchoalveolar lavage fluid
(right panel) shows 4- to 8-μm dark
cyst walls of organisms appearing as
crushed Ping-Pong balls
48

49. Studdiford, JS and Tully AS. USMLE Images for the Boards: Philadelphia. Saunders ,2013
Pneumocystis pneumonia, CXR
 Chest x-ray show a diffuse ground-
glass pattern throughout lungs
 Term ground-glass refers to edge
of a microscope slide that can be
written on with pencil, and it
means that although area remains
transparent, one cannot see detail
through it
 This pattern is characteristic of
pneumocystis pneumonia,
commonly known as PCP
49

50. Progressive multifocal leukoencephalopathy,
microscopic
 PML lesions have perivascular monocyte
infiltrates, astrocytosis with bizarre or
enlarged astrocytes (with occasional mitotic
figures), and central lipid-laden macrophages
 Virus preferentially infects oligodendrocytes
in white matter, leading to demyelination
 Shown here at periphery of lesions are large
“ballooned” oligodendrocytes infected with
JC polyoma virus that have enlarged dark
pink, ground-glass nuclei (arrowhead)
containing viral antigen
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
50

51. Progressive multifocal
leukoencephalopathy, MRI
 PML occurs in immunocompromised
patients, such as those with AIDS, from
reactivation of JC polyomavirus
infection
 Shown here are areas of markedly
increased signal intensity in left
hemisphere (right panel) with T2
weighting, fat saturation
 Extensive white matter involvement is
subtle with T1 weighting,
postgadolinium (left panel)
 multifocal lesions may also involve
cerebellum
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
51

52. Kaposi sarcoma, gross
 Epidemic form of KS seen with AIDS usually appears in
men who have sex with men and is rare in other groups
at risk for HIV infection
 Risk factor for KS is infection with human herpesvirus 8
(HHV-8), known as the Kaposi sarcoma–associated
herpesvirus (KSHV), which can be sexually transmitted
o seroprevalence of HHV-8 is 5% to 10% of general
population, but 20% to 70% in men who have sex
with men
 Lesions can start as small reddish to red-purple plaques
or patches on one or more areas of skin
 Over time lesions may become nodular, larger, and
more numerous
 In patients who test positive for HIV, KS is diagnostic
of AIDS
 Use of antiretroviral therapy markedly decreases
incidence of KS Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
52

53. Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Mycobacterium avium complex infection,
gross
 Seen here in this cross-section of
spleen are numerous small white
nodules representing ill-formed
granulomas
 This patient had disseminated
Mycobacterium avium complex (MAC)
infection, and organs of mononuclear
phagocyte system are often involved
 MAC infection is most likely to occur in
immunocompromised persons, such as
those with HIV infection with CD4
count< 50
53

54. Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Cytomegalovirus pneumonia,
microscopic
 Note very large cells that have large violet
intranuclear inclusions surrounded by a
small clear halo
 This Cowdry type A bodies are typically
referred to as “owl’s eyes” due to their
microscopic appearance
 Basophilic stippling (arrow ) can be seen in
cytoplasm of these cytomegalic cells
 Endothelial and epithelial cells can become
infected
 Though infection may begin in lungs,
dissemination to other organs is
common=CMV retinitis
54

55. Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
HIV encephalitis, microscopic
 HIV infection often involves brain through
macrophages that are carried there from
reservoirs of infection within lymphoid tissues
 Shown here is an encephalitis with a focal lesion
(microglial nodule) showing perivascular
multinucleated cells (arrow), which can be
infected by HIV
 There are few lymphocytes because of markedly
reduced number of CD4 lymphocytes with
progression of HIV infection
 Brain injury is potentiated by microglial
activation and cytokine release
 Encephalitis can lead to progressive loss of
cognitive and motor function, termed HIV-
associated dementia
 Aseptic meningitis may also occur with acute HIV
infection
55

56. Primary central nervous system
lymphoma, MRI
 There is one large periventricular mass (L
arrow ), with smaller masses, showing
increased signal intensity with
gadolinium enhancement
 Areas of lower signal intensity (R arrow )
represent tumor necrosis, and there is
diminished intensity of surrounding
brain from edema
 These lesions often involve deep gray
matter, but also white matter and cortex
 Periventricular spread is common
 They often have extensive central
necrosis
 Most are aggressive diffuse large cell B-
cell lymphomas arising with Epstein-Barr
virus infection in immunocompromised
persons those with HIV infection
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
56

57. Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Cryptosporidiosis, microscopic
 Small round pale blue objects (arrow ) at luminal
border or within a vacuole in peripheral
enterocyte cytoplasm are Cryptosporidium
parvum organisms
 Organisms rarely invade or disseminate
 There is no inflammation, necrosis, or
hemorrhage
 This infection most frequently affects
immunocompromised patients, particularly those
with AIDS
 Immunocompetent patients may develop only a
mild watery diarrhea; but with diminished cell-
mediated immunity, cryptosporidiosis produces a
copious watery diarrhea
 Diagnosis is typically made by examination of a
stool specimen, and organisms can be highlighted
with an acid-fast stain
57

58. Cryptococcal meningitis, gross and
microscopic
 coronal section shows a thick mucoid exudate
within the subarachnoid space ( ), ventricles ( ),
and brain parenchyma ( ) in an
immunocompromised patient with Cryptococcus
neoformans meningitis
 Perivascular collections of organisms can cause
small cystic spaces within the brain
 An India ink stain of CSF (right panel) reveals
thick, clear capsule of these organisms
surrounding these yeasts
 CSF may have a mild to moderate leukocytosis,
elevated protein, and decreased glucose
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
58

59. Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Toxoplasma encephalitis, CT image
 Toxoplasma gondii infection can be
congenital in neonates or an
opportunistic infection of
immunocompromised adults
 This CT scan shows several ring-
enhancing lesions (arrowhead)
with darker areas of surrounding
edema that are typical of
toxoplasmosis producing multiple
abscesses in adults
 Vascularity in organizing wall of an
abscess leads to the observed
bright ring enhancement with CT
and MRI
59

60. Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
Toxoplasmosis, microscopic
 T. gondii infection can result in
formation of pseudocysts, which
occur within an infected cell, with
cell membrane forming the cyst wall
 Pseudocysts ( ) are visible in left
panel within the cerebrum in a
microglial nodule of a patient with
AIDS
 In right panel immunohistochemical
staining with antibody to T. gondii
highlights brown bradyzoites within
the pseudocyst and adjacent free
tachyzoites ( )
 Organisms become progressively
harder to detect as abscessing
lesions become more chronic and
organized
60

61. Marc Imhotep Cray, M.D.
HIV 1 Infection Summary
What is HIV?
 HIV is an RNA retrovirus of the lentivirus genus
 This virus causes acquired immunodeficiency syndrome
(AIDS)
Cause
HIV-1:
o Type M: A-J prevalent in Europe, America, Australia
and sub-Saharan Africa Type
o Type O: mainly in Cameroon
61

62. Marc Imhotep Cray, M.D.
HIV Infection Summary cont.
Transmission
 Unprotected sexual intercourse
 Shared contaminated needles
 Contaminated blood transfusions
 Vertical transmission from mother to child
Virus crosses placenta and is transmitted through breast milk
62

63. Marc Imhotep Cray, M.D.
HIV Infection Summary cont.
 Genes required for viral replication
Remember PEG
 pol : encodes reverse transcriptase and integrase
 env : encodes envelope proteins, e.g. gp120
 gag : encodes viral structural proteins
63

64. Marc Imhotep Cray, M.D.
HIV Infection Summary cont.
Infection process
 gp120 antigen on HIV binds to CD4+ receptors on T cell This
process produces a conformational change and need to bind to a co-
receptor: CCR5 or CXCR4 (no binding=person resistant to HIV)
 gp41 binds to co-receptor This binding causes ‘six-helix bundle
formation’ and fusion of the viral and host membranes
 Disintegration of viral capsid occurs causing viral RNA to be released
into human cell
 Double-stranded RNA is produced and this process is catalyzed by
viral reverse transcriptase
 Double-stranded RNA is integrated into host DNA using integrase
enzyme
 Host cell now manufactures new virions by long terminal repeat
64

65. Marc Imhotep Cray, M.D.
HIV Infection Summary cont.
Investigations
 Bloods: CBC, Electrolytes, BUN/Cr LFTs, lipids, glucose
 HIV specific:
o Enzyme-linked immunosorbent assay (ELISA)
o Western blot test
o Immunofluorescence assay (IFA)
o Nucleic acid testing
 Virology screen: HIV antibody, HIV viral load, HIV genotype,
hepatitis serology, cytomegalovirus (CMV) antibody, STIs
screen
 Other infection, e.g. tuberculosis if indicated
65

66. Marc Imhotep Cray, M.D.
HIV Infection Summary cont.
 Complications
 Increased risk of opportunistic infections:
o Toxoplasmosis
o CMV, e.g. retinitis
o Pneumocystis jiroveci pneumonia
o Cryptococcal meningitis
o Mycobacterium avium complex
o Candida
o Aspergillosis
 Increased risk of malignancies:
o Kaposi’s sarcoma
o Non-Hodgkin’s lymphoma
o Cervical cancer
o Anal cancer
66

67. HIV Antiretroviral therapy
Stages in life cycle of HIV in which antiretroviral therapy is effective are shown.
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013. 67

68. 68
THE END
See next slide for links to tools and resources for further study.

69. Marc Imhotep Cray, M.D.
Sources and further study:
69
 Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier,
2013.
 Dipiro JT et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 8th Ed. New York:
McGraw-Hill, 2011.
 Kishiyama JL. Ch. 3 Disorders of the Immune System, Pgs. 31-59 and Bloch KC. Ch. 4
Infectious Diseases, Pgs. 61-87 In: Hammer GD and McPhee eds. JS. Pathophysiology of
Disease : An Introduction to Clinical Medicine, 7th Ed. New York: McGraw-Hill Education,
2014
eLearning (Cloud)
o Infectious Disease Pathology
o BMS HIV/AIDS Folder
Textbooks:
 Ryan KJ and Ray CG Eds. Sherris Medical Microbiology, 5th Ed. New York: McGraw-Hill, 2010.
 Carroll KC etal. Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th Ed. New York:
McGraw-Hill, 2016.