Opportunistic Infections in HIV

Question 1

Conditions Associated with HIV and/or Antiretroviral Therapy

Answer 1

Cardiovascular
Disease
Kidney Disease
Opportunistic
Infections
Slide credit: Dr Christine Hughes
Bone Disease Cancers Neurocognitive
Disorders

Question 2

Opportunistic infections
defintion

Immune Reconstitution Inflammatory Syndrome (IRIS):

Primary prophylaxis:
secondary prophylaxis:

Answer 2

Opportunistic Infections (OIs):
Infections that occur more often or more severe in people with
weakened immune systems, including people with HIV.
Immune Reconstitution Inflammatory Syndrome (IRIS):
Exaggerated inflammatory reaction to a pathogen when the immune
system begins to recover with antiretrovirals (ART).
It may “unmask” an undiagnosed infection or worsen a previously treated
infection.
Primary prophylaxis:
Medication to prevent initial occurrence of disease
Secondary prophylaxis:
Medication to prevent recurrence of disease

Question 3

Opportunistic infections
* Numerous OIs:

Answer 3

Bacterial respiratory disease Mycobacterium avium complex (MAC)
Cryptococcosis Mycobaterium tuberculosis (TB)
Cytomegalovirus (CMV) Pneumocystis Pneumonia (PJP)
Candidiasis (thrush) Toxoplasma gondii (Toxo)
* Prophylaxis is available for certain OIs:
– PCP (CD4 <200 cells/mm3)
– Toxo (CD4 <100 cells/mm3)
– MAC (CD4 <50 cells/mm3)
* The best protection against OIs is to take ART
More risk as
CD4 decrease

Question 4

Relationship between CD4 and OI risk

Answer 4

> 500 Usual pathogens
200-500
Usual pathogens but more
often than usual (e.g. TB,
thrush, HZ)
<200 PJP
<50-100 MAC, CMV, Toxo, CMV,
Cryptococcus

so it just shows that relationship between CD 4 and your the risk of Oi’s. And so you can see that as the CD 4 drops, there’s a higher risk.

Question 5

Eli is a 54 year-old male who presented to a rural hospital in Alberta
with symptoms of severe shortness of breath and respiratory distress. He was also noted to be febrile on admission (T 38.6). He has a history of 30 pound weight loss over the past 6 months. He has also noticed white patches in his mouth. CT scan of his lungs showed a “ground-glass” appearance. The patient had further testing done and was found to be HIV and HCV positive. His baseline CD4 cell count was 20 cells/µL and viral load was 79 000 copies/mL.

• What is the most likely cause of his pneumonia?
• What additional opportunistic infections would this patient be at risk
  of?
• What are the white patches in his mouth?

Answer 5

ok

Question 6

Pneumocystis Pneumonia (PCP or PJP)

Answer 6

• Pneumonia caused by Pneumocystis jirovecii (formerly P Carinii)
• Fungus ubiquitous to the environment
• 2/3 of healthy children have antibodies by age 2-4 years
• Inhalation of ascospores (airborne transmission)
• Disease can occur by new acquisition or by reactivation of latent infection
• Pre-ART, PJP occurred in 70-80% of patients with AIDS
• 90% of cases in patients with CD4 count <200 cells/mm3
• 20-40% mortality rate
• ART-era, incidence is <1 case per 100 person-years

Question 7

PJP Clinical Presentation

Answer 7

• Progressive dyspnea, fever, non-productive cough,
  chest discomfort
• Subacute onset: worsens over days-weeks (sudden
  onset possible but not common)
• Chest x-ray: diffuse, bilateral, symmetrical “ground
  glass” interstitial infiltrates, butterfly pattern

Question 8

PJP Diagnosis

Answer 8

• Symptoms, blood tests, chest X-ray are NOT specific to PCP
• For definitive diagnosis, need histopathologic/cytopathologic
  demonstration of organisms in tissue:
• bronchoalveolar lavage fluid, or
• induced sputum samples

Question 9

PJP Treatment

Answer 9

Preferred:
* Trimethoprim-Sulfamethoxazole (TMP-SMX)
* (TMP 15-20 mg and SMX 75-100 mg)/kg/day IV q6-8 hours (moderate-severe) or
* TMP-SMX 2 DS tablets PO three times daily (mild-moderate)
* Treatment for 21 days
either orally or Iv. Depending on the severity and the treatments for 21 days.

Alternatives:
* Dapsone plus TMP or
* Primaquine plus clindamycin or
* Atovaquone
* Adjunctive steroids

Dapsone
- Hemolytic anemia can happen
- Happens with G6PD deficiency are more likely to have it
- If you go w it pt need to test for it first

Question 10

PJP Treatment
Monitoring plan:

Answer 10

• Efficacy:
• Improved signs and symptoms, caution IRIS
• Safety (TMP-SMX):
• Adverse reactions high compared to patients without HIV (20-85%)
• Rash (30-55%), Stevens-Johnson
• Fever
• Leukopenia, thrombocytopenia, hepatitis, hyperkalemia
• Renal dosing

Question 11

PJP Prophylaxis
* Primary prophylaxis:
* Secondary prophylaxis:

Answer 11

• Primary prophylaxis:
• Patients with CD4 <200 cells/mm3 (14%)
• Trimethoprim-sulfamethoxazole (TMP-SMX)
• SS 1 tab daily
• DS 1 tab daily or three times weekly
• Alternatives: dapsone, atovaquone, aerosolized pentamidine
• Secondary prophylaxis:
• Start immediately after successful completion of PCP treatment
• Same medications as primary prophylaxis
• Discontinuation of primary or secondary prophylaxis:
• Patient on ART experiences immune recovery
• CD4 > 200 cells/mm3 for ≥ 3 months

Question 12

Toxoplasmic encephalitis (TE)

Answer 12

• TE caused by protozoan Toxoplasma gondii (toxo)
• Seroprevalence of toxo varies, ~11% USA (50-80% in certain countries)
• Disease occurs because of reactivation of latent tissue cysts
• Primary infection occurs after eating undercooked meat (raw shellfish), or oocysts shed in cat feces.
• No person-to-person transmission
• Pre-ART era, 12-month incidence of TE ~33% in patients with advanced immunosuppression who were seropositive
  for T gondii and no prophylaxis.
• All patients with HIV should be tested for IgG antibody to `Toxoplasma soon after diagnosis

Question 13

TE Clinical Presentation

Answer 13

• Primary infection is associated with acute cerebral or
  disseminated disease
• Focal encephalitis:
• Headache, confusion, motor weakness, fever
• Without treatment  seizures, coma, death
• Non-focal:
• Non-specific headache and psychiatric symptoms

Question 14

TE Diagnosis

Answer 14

• Ig G antibodies PLUS
• CT or MRI

they do, imaging to look for signs and brains. You can see these dots here, but you also need to have the Toxo, ig. Ig. Antibody. So it’s a combination of both. If you haven’t got the antibody. If you haven’t got that bug in your system, changes in the brain would be for another reason.

People don’t typically biopsy the the brain unless they really have to. So it’s only in circumstance. If somebody has ig antibodies and the signs you would assume that it be more likely that it would be te then it would be lymphoma

Question 15

TE Prevention and Management - When

Answer 15

Primary Prophylaxis Toxoplasma IgG positive + CD4 < 100 cells/uL
Discontinue when CD4 > 200 cells/uL x 3 mos (from ART)
OR CD4 100-200 cells/uL and HIV RNA undetectable x 3-
6mos

Treatment Treat for 6 weeks or longer if incomplete clinical and
radiological response at 6 weeks
Chronic maintenance therapy after acute treatment

Maintenance therapy
(secondary prophylaxis)
Start immediately after acute treatment
Discontinue when CD4 > 200 cells/uL x 6 mos (from ART)
AND remain asymptomatic

Question 16

TE Prevention and Management - What

Answer 16

Primary Prophylaxis: TMP-SMX 1 DS PO daily

Treatment: pyrimethamine 50-75 mg PO daily +
sulfadiazine 1000-1500 mg PO q6h +
leucovorin 10–25 mg PO daily

Maintenance therapy (secondary prophylaxis): Pyrimethamine 25–50 mg PO daily +
sulfadiazine 1000-2000 mg PO BID +
leucovorin 10–25 mg PO daily

Maintenance doses are lower than therapy doses

Pt can be treated with septra and then septra fro maint tx too

Question 17

Mycobacterium Avium
Complex Disease (MAC)

Answer 17

• MAC disease is caused by Mycobacterium avium
  complex (MAC)
• Slow growing bacteria
• Ubiquitous to the environment
• Transmitted through inhalation or ingestion of
  MAC bacteria
• Pre-ART, 20-40% of people with HIV with
  advanced immunosuppression, rare in ART era

it’s transmitted, but it can be both inhaled, or it can be adjusted to. So some people just have Mac and their gi track, and it doesn’t mean they have an infection.

this infection can be in multiple organs. So again, it’s something that happened much more commonly in the pre art area, and we really don’t see a ton of it.

Question 18

MAC Presentation and Diagnosis

Answer 18

• Clinical presentation:
• Disseminated, multi-organ infection (localized may be seen)
• Fever, night sweats, weight loss, fatigue, diarrhea
• Localized manifestations (symptoms vary by site)
• Diagnosis:
• Isolation of MAC in blood cultures (or other tissue including lymph nodes,
  bone marrow etc.)
• Possible colonization in respiratory or GI tract that is not indicative of disease
• MAC is slow growing and cultures should be watched for growth for 4-6 weeks

can be in different organs. And so you do get local manifestations based on where it is. But often people are sick for a while before they really get down to it,

to diagnose that you really need to isolate this bug, and they do it typically in blood cultures. But it can be in other tissues as well. And again, colonization and gi track doesn’t mean that they have disease. So you got to watch out for just that colonization versus it actually being infectious.

Slow growing: so if you get a Mac blood culture and no growth in 1 week, what does that mean for you?
It doesn’t mean a whole lot. Yeah. So yeah, it should be watched for 4 t0 6 weeks.

Question 19

MAC Prophylaxis

Answer 19

• Primary prophylaxis:
• NOT recommended for people on ART
• Patients not on ART should receive prophylaxis if
• MAC blood culture negative
• CD4 <50 cells/mm3
• Preferred: Azithromycin 1200 mg once weekly or clarithromycin 500 mg bid
• Alternatives:
• Rifabutin
• Discontinuation of primary prophylaxis:
• Effective ART

Question 20

MAC Treatment and maintenance therapy

Answer 20

• Treatment and maintenance therapy (secondary prophylaxis):
• Clarithromycin 500 mg bid + ethambutol 15 mg/kg PO daily or
• Azithromycin 500-600 mg daily + ethambutol 15 mg/kg PO daily
• Third or fourth agent: rifabutin, fluoroquinolone, aminoglycoside
• Discontinuation of secondary prophylaxis:
• Completed at least 12 months of therapy
• No signs and symptoms of MAC disease
• CD4 >100 cells/mm3
  for >6 months

This is a bacteria:
One of the criteria with having the low CD. 4 is also that the blog culture is negative. So we don’t want that. We want to make sure they don’t have Mac before we start. So you’ve got to wait these 6 weeks. Make sure the blood culture is negative

if you start treatment with azithro for prophylaxis, and then it turns out they do have Mac because it’s a bacteria. You’ve got a risk of developing resistance.