What pathogens does CD4 cell mediated immunity protect us against?
Fungi, mycobacterium, viruses and protozoa.
Non-opportunistic infections that can occur at any CD4 count
VZV, bacterial pneumonia, cryptosporidium, Tb.
Common opportunistic infections seen in Africa compared to the US
US has lots of pneumocystis. Africa has lots of Tb and cryptococcus.
Pathogenesis of IRIS
Increased function of CD4 cells results in a brisk immune response to underlying pathogens. This may also result in a hypersensitivity reaction to any existing microbe (fever, dyspnea, cough)
A 25 year old presents with respiratory distress and pneumonia. Azithromycin and ceftriaxone are ineffective. Sputum and gram stain are negative. He is an IV drug user and the rapid HIV test was positive. CD4 count is
Pneumocystis jirovecii pneumonia (PCP) requires TMP-SMX. Note that the CXR shows typical diffuse interstitial infiltrates and “ground glass appearance”.
Best was to dx PCP
Monoclonal Ab, silver stain is also used. PCR is not used because it can also colonize the posterior nasopharynx.
What happens when you treat someone with PCP?
They tend to get worse before they get better and you can mitigate inflammation with corticosteroids. Additionally, watch fluids b/c IV bactrim is a large fluid load and can cause heart failure if they already have pneumonia.
When do you consider adding corticosteroids to TMP-SMX in an HIV patient with PCP? What are risks of this?
pO2 < 70 or A-a gradient > 35. Risk include further immunodeficiency causing HSV reactivation and oral thrush
When do you give someone prophylactic bactrim for PCP?
CD4 < 400, oral thrush not related to steroids or abx, other opportunistic infections, prior PCP. Prophylaxis can be stopped if on ART when viral load is 0 and CD4 > 200.
Other options for PCP prophylaxis instead of bactrim?
Aerosolized pentamidine minimizes marrow suppression caused by bactrim. However, not that there is a high breakthrough rate in AIDS patients. Dapsone (check G6PD first to prevent hemolytic anemia) and atovaquone can also be used.
A 30 year old man with AIDS has a high viral load and a CD4 of 80. He has a seizure and is hemiparetic. MRI shows multiple brain enhancing lesions. What is causing his condition? What would you see on histology?
Eating undercooked meat (especially lamb) and cat exposure can transmit toxoplasmosis. This is the most common CNS space occupying lesion in AIDS patients. On histology you would see necrotizing granulomas with tachyzoites and cysts after peroxidase stain.
Puppies with diarrhea born on a farm causing illness in HIV patients
Bird droppings causing infection in HIV patients
Turtles causing infection in HIV patients
Salmonella, also avoid raw/undercooked eggs
Fish tanks causing skin nodules in immunocompromised patients
Atypical Tb (M. marinum)
Undercooked meats causing illness in immunocompromised patients
Listeria (+unpasteurized products) and toxoplasmosis
Drinking surface water causing illness in immunocompromised patients
Giardia or cryptosporidium
Differential for ring-enhancing lesion in an HIV patient
Toxoplasmosis, Tb and cryptococcus cause multiple enhancing CNS lesions. CNS lymphoma usually has one lesion
Tx for toxoplasmosis
Pryimethamine/sulfadiazine: synergistically block folic acid metabolism and add leucovorin to rescue other cells. Check with imaging and CD4 cells to see if lesions go away. Steroids are also used if there is midline shift.
Prophylaxis against toxoplasmosis if HIV patient has CD4 < 100
AIDS patient presents with headache, fever and cranial nerve palsy. LP results are shown below. How do you treat him?
Any CNS palsy makes you think of a basilar meningitis like cryptococcus meningitis. Tx with AmphoB or 5FC and do LP to lower intracranial CSF pressure to cure cranial nerve palsies. Eventually you switch them to an oral azole.
30 year old AIDS patient presents with flashing lights in the periphery, difficulty swallowing, a fever and a new hepatitis. CD4 count is less than 200. She is leukopenic and has atypical lymphocytosis. Fundoscopic exam is shown below.
Note the exudates and hemorrhages following the vessels indicated CMV retinitis. Reactivation CMV can cause esophagitis, retinitis and hepatitis when the immune system begins to wane. Note that IRIS can also cause CMV retinitis once ART is started.
Where does CMV most often come from?
Kids in daycare, they tend to endure the infection well, but adults don’t.
Screening for CMV activation in HIV patients
Dilated eye exam
Tx for CMV retinitis
Oral valganciclovir. Ganciclovir caused bone marrow suppression and has to be given IV. Foscarnet has to be given IV
Drug used to treat acyclovir resistant HSV because of mutated thymidine kinase
When to prophylax against CMV retinitis
It is not standard of care to prophylax against CMV retinitis
A 40 year old woman with AIDS comes in with fever, diarrhea, weight loss and night sweats. Her CD4 is < 100. Stool has acid-fast bacilli, Hgb 7, Hct 25, WBC 1.5, pot 89k, alk phos 850, ALT 130, AST 80 and hyperbilirubinemia. Physical exam reveals hepatosplenomegaly. After ruling out lymphoma, what is your most likely diagnosis?
MAC (Mycobacterium Avium Complex). It is ubiquitous and is usually acquired via fruits/vegetables and rarely respiratory. Consequently diarrhea is the 1st presentation. Acid-fast bacilli get into the marrow and cause marrow suppression.
When do you start prophylaxis against MAC?
< 50 CD4 T-cells.
+ culture from any site (blood, marrow or liver).Note that there is a special culture tube that promotes lysis of WBC to increase yield (isolator tube).
Tx for MAC
At least 2 effective drugs! #1) Clarithromycin and azithromycin as an alternative. #2) Ethambutol. Possibly adding on rifabutin/rifampin, ciprofloxacin or amikacin. Note that INH and PZA (pyrazinamide) have no activity against MAC. USE MACrolides!
What do you need to do if you give a patient clarithromycin and ethambutol to treat MAC?
Optic neuritis is a side effect of ethambutol.
Prophylaxis for MAC
Azithromycin (macrolide) or clarithromycin until CD4 gets > 100 with no detectable viral load.