Opportunistic Infections in HIV

1. CLINICAL CASE
• A 26 year old male comes to the ER for
SHORTNESS OF BREATH.
• He says this has been going on for about 3
weeks already. It started with feeling more
tired than usual when climbing up the stairs.
• Today he feels almost unable to walk anymore
from bed to bathroom.

2. CLINICAL CASE
• Our patient admits to having a cough of about 4
weeks already. It’s a dry cough, almost no
phlegm.
• He also has on and off fever through all this
period, which would go away if he took
paracetamol.
• When asked he says he also has loose stools
which he attributes to the new supplements he
has been taking. He would go to the bathroom 5x
a day. The stools are watery.

3. CLINICAL CASE
• Our patient was a school athlete when he was
in college.
• He now works for a start up company but has
been unable to go to work for the last week.
• He does not smoke, nor drink alcohol.
• He denies using drugs.
• He has had 3 partners in the past: 2 males and
one female.

4. CLINICAL CASE
• On exam, our patient looks ill and tired.
• His VS: BP 110/80; HR 110; RR 36; T 38.5
• He is awake and can talk in brief sentences.
• He has no jaundice. His skin appears dry and
rough with scattered papules.
• He has several cervical lymph nodes. His
mouth has a thick layer of white thrush over
upper palate and tongue.

5. CLINICAL CASE
• His lung sounds have crackles and rhonchi
over all lung fields. His heart sounds are
tachycardic but no murmurs.
• His abdomen is scaphoid. Mild area of
tenderness in the lower abdomen.
• All extremities are moving full range. No focal
neurologic deficits.
• No edema. No joint effusions. No cyanosis.

6. COMMON OPPORTUNISTIC
INFECTIONS IN HIV
Regina Berba MD
UP PGH

8. Basic Immunopathology of HIV:
Destruction of CD4 helper cells

9. HIV and PROGRESSION TO AIDS

10. Natural History of
Typical HIV-1 Infection Without Treatment

11. HOW HIV ATTACKS YOUR BODY

13. OPPORTUNISTIC INFECTIONS (OI)
• Ois are a heterogenous group of infection that
occur more in immunocompromised states
• Caused by viruses, bacteria, fungi, protozoans,
helminths & other life forms
• OIs tend to be more severe and disseminated
• OIs usually require longer RX
• OIs in HIV assoc with specific CD4 counts

15. Relevant Opportunistic Infections in
the Philippines

17. Typical Relationship of Clinical Manifestations to
CD4 Count in HIV Infected Patients
50
Lymphoma
Tuberculosis
Kaposi Sarcoma
Herpes Zoster

18. In the Philippines: TOP 9 OIs
(n=478)
RANK OI % Prevalence Mean CD4 Mortality %
1 PTB 15.3 161 6.8
2 PCP 10.5 86 8
3 ePTB 5.7 160 0
4 disseminated TB 2.3 30 9.1
5 oral Thrush 2.3 136 9.1
6 CMV 1.9 48 11.1
7 Cryptococcal
Meningitis
1.3 35 16.7
8 Esophageal
Candidiasis
1.2 64 0
9 Toxoplasmosis 0.8 13 0
Salvana et al 2012

19. Approach to Patients with Cough:
DIAGNOSTIC CLUES
PARAMETER PRESENTATION
Duration of Symptoms Acute : bacterial pneumonia
Chronic: TB, PCP
Presence of fever Often present
If absent: non infectious cause like CA
Character of phlegm Purutent: Bacterial pneumonia, TB
Scanty: PCP, Viral pneumonia, Atypical
Pneumonia, TB
Chest Xray Typical: Bacterial pneumonia, TB
Atypical: TB, PCP

20. Approach to Patients with Cough
• Chest Xray
• Sputum tests:
– Gram stain, CS
– Sputum for GenXpert MTB
– Induced Sputum for PCP PCR or PCP Antigen
– Bronchoalveolar Lavage (BAL) studies
• Other Labs: CBC, LDH, ABG
• CT Scan Chest

21. EMPIRIC THERAPY FOR PATIENTS WITH COUGH
EVALUATE THE PATIENT AND COVER FOR
INFECTIONS YOU ARE HIGHLY CONSIDERING:
• Always prudent to cover for bacterial CAP
(PSMID guidelines) – lifesaving
• TMP-SMX is drug of choice if PCP is strongly
suspected (+ Prednisone if hypoxemic)
• HRZE best started when more information
becomes available.

31. GenXpert MTB
• Sensitivity approaches 100%
• Specificity for Rifampicin resistance: 92%
• Turn around time: 1 hr 40 min
• Takes cartridges loaded with
sputum and reagents.
The cartridges consist of a
syringe barrel, a sonicator dome,
a reverse-transcriptase PCR tube
and a rotary valve

32. HIV/AIDS and TB:
A Deadly Combination
• HIV suppresses the human immune system.
• TB suppresses the human immune system.
• Each makes the other worse synergistically.
• The number of new cases of TB has more than
doubled in countries with high HIV prevalence in
the past decade
One in four HIV
deaths is linked to TB
+

33. Pneumocystis Jiroveci
(Formerly P. carinii)
• Taxonomy
– Fungus (before was considered) Protozoan
• Epidemology
– Environmental source
• Transmission
– Respiratory
• Usually in HIV with CD4 less than 200
• Recommended Prophylaxis- TMP/SMX (160/800)
• Alternative agents- Dapsone

36. PCP Pneumonia: Treatment
• Drug of CHOICE for PCP:
- Typical oral dose TMP/SMX or Cotrimoxazole Forte
160/800 2tablets 3x a day for 21 days
- If IV formulation is available give as 5mg/kg IV q 8
of the trimethoprim component for severe disease
+/- Corticosteroids are added for patients with
hypoxemia.
• Alternative Drugs if with hypersentivity
- Clindamycin 300-450mg po/IV q6-q8 +
Primaquine 30mg qday for 21 days

37. Toxicities to watch out for when
treating for PCP
Drug Issues
TMP-SMX Toxicities: ↓WBC, ↓Plat, ↑LFT
↑Creat, ↑Amylase, rash, fever
Cross reactivity: dapsone (+/-
50%)
Clindamycin + Primaquine Rash, LFT, diarrhea
Methemoglobinemia
Hemolytic anemia (G-6-PD)
Dapsone Rash, fever, ↑LFT, Hemolytic
anemia (G-6-PD), peripheral
neuropathy

38. CLINICAL CASE
Our 26 patient was found to have a CD4 = 23
and bilateral interstitial infiltrates on CXR has
been started on treatment with cotrimoxazole
forte plus prednisone for presumptive PCP.
On the 5th day he still dyspnea and reports
that his symptoms have not improved since
admission to the hospital.
What can you do?

39. Management of Patients with AIDS Related PCP
Not improving on TMP-SMX
• Add corticosteroids if not already done
• Send sputum specimens if not yet done
• Reassess diagnosis
– Is PCP correct?
– Are there any other pathogens? TB?
• Explain to patient and family
– Realistic assessment of prognosis
– May need home oxygen

40. PCP Primary Prophylaxis
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

41. Discontinuation and Restarting Primary Prophylaxis
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

42. PCP Secondary Prophylaxis
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

43. CLINICAL CASE: Other Problems
• Lesions in the mouth: Oral Candidiasis
– Usually CD4 < 200
– Associated with high viral loads
• Diagnosis: Clinical
– If there is doubt, KOH stain
– If esophageal candidiasis is suspected: scope
– If resistance to usual treatment is suspected: Fungal
CS
• Treatment: Fluconazole 100-200mg once daily for
7-14 days

46. Evaluation of HIV-patient with
Diarrhea
• Diarrhea due to multitude of etiologies
• Infectious, Malignancy or medication-induced
• Incidence decrease with use of potent ARVs

47. Causes of Diarrhea in Patients suspected to have HIV
Protozoal Gut neoplasms Bacterial
Microsporidium*
Cryptosporidium*
Isospora belli
Giardia lamblia
Entamoeba histolytica
Leishmania donovani
Blastocystis hominis
Cyclospora sp
Lymphoma
Kaposi's sarcoma
Salmonella*
Campylobacter*
Mycobacterium avium compl
Clostridium difficile
Shigella
Small bowel bact overgrowth
Vibrio sp
Tumor invasion
Lymphoma
Kaposi's sarcoma
Viral Pancreatic insuff Fungal
Cytomegalovirus*
Herpes simplex
Adenovirus
Rotavirus
Norwalk
HIV
Infectious pancreatitis
Cytomegalovirus
Mycobacterium avium
complex
Drug-induced pancreatitis
Didanosine
Pentamidine
Histoplasmosis
Coccidiomycosis
Idiopathic
"AIDS enteropathy"

48. Possible Enteric Pathogens
Pathogen Small bowel Colon
Bacteria
Salmonella*
Escherichia coli
¶
Clostridium perfringens
Staphylococcus aureus
Aeromonas hydrophila
Bacillus cereus
Vibrio cholerae
Campylobacter*
Shigella
Clostridium difficile
Yersinia
Vibrio
parahaemolyticus
Enteroinvasive E. coli
Plesiomonas
shigelloides
Klebsiella
oxytoca(rare)
Virus
Rotavirus
Norovirus
Astrovirus
Cytomegalovirus*
Adenovirus
Herpes simplex virus
Protozoa
Cryptosporidium*
Microsporidium*
Cystoisospora
Cyclospora
Giardia lamblia
Entamoeba
histolytica

49. Diagnostic Studies
Stool
Exam
culture of bacteria
C. difficile toxin assay
examination for ova and parasites
AFB or immunofluorescent stain
(Cryptosporidium, Isospora, and Cyclospora)
 trichrome staining (Microsporidium)
Blood
culture
 Bacterial
 Fungal
Endoscopy  small bowel biopsies looking for MAC, lymphoma, or
microsporidiosis
 colonoscopy and biopsy: CMV or other inflammatory
enteridites, Kaposi’s sarcoma
 Lower endoscopy: classic features of colitis
 Upper endoscopy: symptoms suggesting enteritis
Imaging  abdominal computed tomography (CT) using oral and
intravenous contrast

51. Common Opportunistic Infections presenting with diarrhea
Causative
Organism
Transmission Presentation Diagnostic study Treatment
Microsporidia
-obligate
intracellular
Protozoan
fecal-oral route
via ingestion of
spores
anorexia, nausea,
weight loss,
abdominal pain,
malabsorption,
fever and chronic
non-bloody
diarrhea
Stool exams using
light microscopy
with Kinyoun
staining
Albendazole (400
mg PO BID x 3
weeks)
Cyclospora
-coccidian
protozoan
consumption of
untreated water
and
contaminated
food
Acute or chronic
diarrhea, fatigue,
weight loss,
nausea, fever,
vomiting
Stool modified
Kinyoun staining
TMP-SMX
160/800 mg
orally four times a
day for 7–10 days
Cryptosporidiu
m
-intracellular,
protozoan
ingestion of
oocysts from
contaminated
drinking
or recreational
water, sexual
contact
acute, chronic, or
fulminant
diarrhea,
acid-fast staining
modified
AFB/Kinyoun
stains
No antibiotics are
currently
recommended
Started on
ARV therapy
immediately to
improve
Philippine Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Opportunistic Infections in Human
Immunodeficiency Virus-Infected Adults and Adolescents in the Philippines

52. CLINICAL CASE 2
A 28 y/o man is brought to the ER after a
witnessed seizure. Family members report
that he has had some memory loss and
unusual behavior for the past 2 weeks.
The patient is an English teacher.
On PE he is confused and disoriented. Weakness
was noted in the R upper and lower
extremities.

56. Evaluation of CNS Mass Lesions in
Suspected HIV Patients
Toxoplasmosis
Lymphoma
PML
Tuberculosis
Fungus
Nocardia
Bacterial
Syphilis
Kaposi Sarcoma
Glioblastoma
Radiologic
non specific
extra CNS lesions
Laboratory
Serology – Toxo IgG, crypt Ag
Blood culture – AFB, fungus
CSF – Crypt Ag, CMV PCR, EBV PCR
Urine – Histo Ag
Empiric Therapy

57. Toxoplasmosis
• Toxoplasma gondii
• Carried by cats, birds and other domesticated
animals; soil contaminated by cat feces, and in meat
• Most common site is the brain
• It can infect lungs, retina of the eyes, heart, pancreas,
liver, colon and testes

58. Toxoplasmosis - Diagnosis
• Definite diagnosis: Biopsy with demonstration
of tachyzoites
• Stereotactic biopsy of the brain often difficult
to do
• Presumptive diagnosis acceptable when
– CD4 < 100
– Compatible neurologic disease
– No prophylaxis
– Serology: positive toxo IgG

62. Toxoplasmosis
Therapy:
• Sulfadiazine + Pyrimethamine + Folinic acid
• Clindamycin + Pyrimethamine + Folinic acid
• Atovaquone + Pyrimethamine + Folinic acid
• Azithromycin + Pyrimethamine + Folinic acid
• Atovaquone + Sulfadiazine

63. Cryptococcal Infections
• Cryptococcus neoformans
• Areas heavily contaminated with bird excrement.
• Infects meninges, skin and lungs
• Signs and symptoms
• Diagnosis and prognosis
• Therapy: - Amphotericin-B +/- Flucytosine
- Fluconazole +/- Flucytosine
- Itraconazole

66. CLINICAL CASE 3
• A 40 year male diagnosed HIV + 3 years ago and
lost to followup.
• He now complains of headache for the last 2
months
• Two days ago now with behavioral changes, fever,
vomitting.
• He has lost over 20kg in the last 6mos.
• He has no cough.
• His CD4 count is 200.

68. HIV and EPTB
• Immunosuppression increases infection and makes
its symptoms become atypical
• TB: most cause of death in 24-44 y/o AIDS
• EPTB occur in 40-80% in HIV(+).
• Lymph node involvement is the most
• Miliary, CNS or cutaneous TB are more than HIV(-)
• Multi drug-resistant TB

69. Mycobacterium tuberculosis: EPTB
• CD4 count threshold: - Any CD4 count
• For TST (+) > 5 mm
- Anergic but with high risk
- Known exposure to active case
• Recommended prophylaxis - INH 300mg/day
+ Vitamin B6 x 6months

70. Mycobacterium tuberculosis
Therapy:
First line drugs: Second line drugs:
- Isoniazid - Ethionamide
- Rifampin - Ofloxacin, Ciprofloxacin
- Ethambutol - Streptomycin
- Pyrazinamide - Cycloserine
- Capreomycin
- Kanamycin

74. TB Lymphadenitis

75. Gastrointestinal TB: LIVER

76. TB of the Pericardium

77. TB of the Pericardium

78. TB of the skin

80. MILIARY TB

81. HIV associated CMV Disease
Pre-HAART, 30% of patients developed:
– Retinitis
– Colitis
– Others:
• Pneumonitis
• Ventriculoencephalitis
• Myelitis
• Radiculomyelopathy
• Adrenalitis

82. Diagnosis of CMV Disease
• Serology (IgG, IgM)
• Viremia common in asymptomatic persons with
low CD4/ CMV Antigenemia)
• Histology required for diagnosis of colitis and
pneumonitis
• ‘owl’s eye ‘ intranuclear inclusion bodies pathognomonic
• Rare cells in the absence of clinical disease insignificant
• Retinitis clinical diagnoses
• Fluffy exudate
• CNS – CMV PCR

83. Cytomegalovirus Infections
• CD4 count threshold: <50 cell per uL
< 100 cells per uL if prior OI
<CMV antibody positivity
• Ophthalmologic evaluations should be done

86. Multifocal CMV
Retinitis

89. Cytomegalovirus Infection
Therapy:
• Ganciclovir PO or IV or intraocular
• Valganciclovir (oral)
• Foscarnet IV
• Cidofovir IV + Probenecid

90. Mycobacterial Infections Other than TB
(MOTT)
• Atypical mycobacteria
• Can cause a wide variety of infections such as
abscesses, masses, sinus infections.
• They can also can infect the lungs, lymph
nodes, bones, gastrointestinal tract, skin and
soft tissues.
• Nosocomial infections

91. Mycobacterium avium intracellulare
• Mycobacterium avium complex and
immunosupression
• Sources are food, water, and soil
• Localized or disseminated infection
• Symptoms of fever, weight loss, night sweats, fatigue,
anemia, loss of appetite, loose stools or diarrhea,
abdominal pain, enlarged liver or spleen

92. Mycobacterium avium
• CD4 count threshold - 50 cells per uL.
• Recomm. prophylaxis - Azithromycin or
- Clarithromycin
• Alternative agents - Rifabutin
- Azithromycin + Rifabutin

93. Symptoms and Diagnosis
• Variety of symptoms
• Diagnosis based on isolation of MOTT from
site affected

94. Mycobacterium Avium
Therapy:
• Clarithromycin + Ethambutol +/- Rifabutin
• Azithromycin + Ethambutol +/- Rifabutin
• Alternatives as second line drugs:
Ciprofloxacine,
Ofloxacine, Amikacin, Kanamycin.

95. How patients with advanced HIV infection/AIDS
may present to our clinics
• Pulmonary diseases
– Pneumocystis pneumonia
– Tuberculosis
– Pneumococcal pneumonia
• Central nervous system
– Toxoplasmosis
– Cryptococcosis
– Cytomegalovirus
• Gastrointestinal diseases
– Salmonella
– Cryptosporidiosis
– Other parasitic infections
• Eyes
– Cytomegalovirus
• Disseminated diseases
– Disseminated TB
– Mycobacterium avium
intracellulare
– Bacterial infections (e.g.
salmonellosis)
• Skin
– Candidiasis
– Kaposi’s sarcoma
• Immune system
– Non-Hodgkin’s lymphoma

96. Common Infections of advanced HIV
infection/AIDS by pathogen
• Fungal diseases
– Pneumocystis pneumonia
– Oral and esophageal
candidiasis
– Cryptococcosis
• Mycobacterial diseases
– Mycobacterium tuberculosis
– Mycobacterium avium
intracellulare
• Protozoal diseases
– Toxoplasmosis
– Various gastrointestinal
pathogens
• Viral diseases
– Cytomegalovirus
– Epstein-Barr virus
– Human herpes virus 8
• Bacterial diseases
– Streptococcus pneumoniae
– Salmonellosis