Prior to Question 19 from the first paper of 2015, this topic has never been examined in the written paper, but an entire chapter of Oh's Manual is dedicated to it. Also, the college at one stage did ask the candidate to "List the potential causes of diffuse pulmonary infiltrates in a patient with AIDS" (Question 9 from the first paper of 2003). Subsequently, in Question 20 from the second paper of 2018, they focused on IRIS (Immune Reconstitution Inflammatory Syndrome), a relatively rare complication of highly active antiretroviral therapy.
Anyway, it seemed important to include a summary of it in the Required Reading section.
Unless otherwise stated, the information below is derived from Oh's Manual.
Recommended alternative sources for this topic could include the following:
Oh's chapter has a graph very similar to this.
For those who don't like colourful graphs, here is a boring grey table:
Stage |
CD4 count per μL |
Characteristic features |
Incubation |
normal (1000) | none |
Seroconversion: 1-4 weeks post exposure |
1000-500 |
|
Early disease |
1000-500 |
|
Intermediate disease |
500-200 |
|
Advanced disease |
under 200 |
|
Issues related to chronic HIV infection are all very interesting, but largely irrelevant to the ICU environment. The choice of antiretroviral drugs and chronic disease monitoring will not interest the pragmatic intensivist, and the CICM candidate cannot be expected to have anything more than a workmanlike understanding of these issues. They are presented below with little detail.
Diagnosis
|
Monitoring
|
In other words, as if answering Question 19 from the first paper of 2015, "what relevant information about the patient’s HIV disease would you elicit from the history, examination and investigations to assist management?"
The college answer has been remixed with some additional suggestions.
History Prognosis-defining features:
|
Examination
|
Investigations
|
Question 19 from the first paper of 2015 also wants us to "discuss the issues associated with the administration of antiretroviral therapy in the Intensive Care Unit"
These drugs are far from benign:
Pneumocystis:
Cryptococcus neoformans meningitis:
Toxoplasma encephalitis:
One day, a CICM fellowship question may ask the candidate to discuss the issues related to the management of a critically ill patient with advanced HIV infection. A systematic approach would be called for. One might even be invited to tabulate one's answer.
Airway:
Respiratory issues:
Circulatory issues:
Central Nervous System problems
Endocrine and electrolyte derangement
Renal impairment
Gastrointestinal complications:
Haematological problems
This is the exuberant inflammatory response which develops within days or weeks of the commencement of antiretroviral therapy. The immune system, awakening from its stunned state, finds the body overrun by the likes of Pneumocystis, and reacts violently. A more formal definition is asked for in Question 20 from the second paper of 2018, where the model answer characterises it as:
"a collection of inflammatory disorders associated with paradoxical worsening of pre-existing infectious process following initiation of antiretroviral therapy primarily in HIV-infected patients"
"Paradoxical worsening of an existing infection or disease process" is also the description given to this disease state by Sharma & Soneja (2011). In fact, there does not appear to be an agreed-upon gold standard of definition in the literature. Suggested definitions (French et al, 2004; Robertson et al, 2006) generally require some combination of the following features:
Obviously such HIV-centric definitions do not take into account the fact that IRIS can occur in several other conditions (eg. with tuberculosis).
Pathogenesis of IRIS is well-described in the IRIS article from UpToDate, from which the college answer to Question 20 from the second paper of 2018 appears to draw most of its inspirations. For the purposes of regurgitating a point-form summary of what happens, the causes of IRS can be summarised thus:
Risk factors for IRS (according to Shellburn et al, 2005) include:
Differential diagnosis (From Beshuizen et al, 2009):
Clinical manifestations may include:
Management of IRIS (ffrom Konishi et al, 2010)
Oh's Manual: Chapter 68 (pp. 710) HIV and acquired immunodeficiency syndrome by Alexander A Padiglione and Steve McGloughlin
Zolopa, Andrew R., et al. "Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial." PloS one 4.5 (2009): e5575.
Huang, Laurence, et al. "Intensive care of patients with HIV infection." New England Journal of Medicine 355.2 (2006): 173-181.
Murdoch, David M., et al. "Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options."AIDS research and therapy 4.1 (2007): 9.
Bajwa, Sukhminder Jit Singh, and Ashish Kulshrestha. "The potential anesthetic threats, challenges and intensive care considerations in patients with HIV infection." Journal of pharmacy & bioallied sciences 5.1 (2013): 10.
Duggal, Abhijit, et al. "OUTCOMES OF HIV PATIENTS REQUIRING INVASIVE MECHANICAL VENTILATION AS COMPARED TO PATIENTS WITH AIDS." CHEST Journal 136.4_MeetingAbstracts (2009): 115S-a.
Mayer, Kenneth H., and Martyn A. French. "Immune reconstitution inflammatory syndrome: a reappraisal." Clinical Infectious Diseases 48.1 (2009): 101-107.
Sharma, Surendra K., and Manish Soneja. "HIV & immune reconstitution inflammatory syndrome (IRIS)." The Indian journal of medical research 134.6 (2011): 866.
French, Martyn A., Patricia Price, and Shelley F. Stone. "Immune restoration disease after antiretroviral therapy." Aids18.12 (2004): 1615-1627.
Robertson, Jaime, et al. "Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy." Clinical infectious diseases 42.11 (2006): 1639-1646.
Shelburne, Samuel A., et al. "Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy." AIDS 19.4 (2005): 399-406.
Beishuizen, S. J., and S. E. Geerlings. "Immune reconstitution inflammatory syndrome: immunopathogenesis, risk factors, diagnosis, treatment and prevention." Neth J Med 67.10 (2009): 327-331.
Konishi, M., K. Uno, and E. Yoshimoto. "Management of immune reconstitution inflammatory syndrome." Nihon rinsho. Japanese journal of clinical medicine 68.3 (2010): 508-511.
Richaud, Clémence, et al. "Anti-tumor necrosis factor monoclonal antibody for steroid-dependent TB-IRIS in AIDS." Aids 29.9 (2015): 1117-1119.
Lwin, Nilar, Michael Boyle, and Joshua S. Davis. "Adalimumab for corticosteroid and infliximab-resistant immune reconstitution inflammatory syndrome in the setting of TB/HIV coinfection." Open forum infectious diseases. Vol. 5. No. 2. US: Oxford University Press, 2018.