Human Immunodeficiency Virus (HIV) and AIDS
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). 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:
- A good 2006 NEJM article on the "Intensive care of patients with HIV infection."
- A 2013 overview of the organ system complications of HIV
Microbiology of HIV
- A lentivirus (one of the Retroviridae)
- Single-strand enveloped RNA virus, about 120nm in diameter (large for a virus)
- Comes in 2 flavours: Type 1 and Type 2
- Type 1 is the one which causes the majority of HIV infections
- Type 2 is less infective and mainly confined to West Africa
- Inside the host cell, the viral RNA is reverse-transcribed into DNA by a viral reverse transcriptase enzyme.
- Proviral DNA is then integrated into the host DNA by a viral integrase enzyme.
- Proviral DNA is transcribed into RNA when the cell is activated, resulting in the assembly of new viral particles.
Chronology of infection and complications
Oh's chapter has a graph very similar to this.
For those who don't like colourful graphs, here is a boring grey table:
CD4 count per μL
1-4 weeks post exposure
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.
Issues of interest to the intensivist
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.
Commencement or continuation of antiretroviral therapy during a critical illness
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"
- If they are already on antiretroviral drugs, those should continue.
- None are parenteral.
- Many of them won't get absorbed properly (all are capsule drugs)
- Alkalinised stomach content will not permit adequate absorption
- Feeds need to be paused for the administration of many of them, leading to sub-optimal nutrition.
- Metabolism and clearance will be altered
- Some will interact with ICU medications (eg. protease inhibitors potentiate the effects of midazolam)
- If they are not on antiretroviral drugs, and are admitted for some non-HIV related problem, then one can safely defer starting them until after the critical illness has resolved.
- They may not know they have HIV. Up to 40% of patients admitted to ICU with a complication of HIV don't know they are infected.
- If they are admitted with an infectious complication of untreated HIV, then antiretroviral drugs should be started as early as possible (it seems to result in less AIDS progression and decreased mortality with no increase in adverse events)
- Exceptions to this rue are cryptococcal meningitis and TB meningitis, because:
- Drug interactions are prohibitive.
- A severe inflammatory syndrome (Immune Reconstituion Inflammatory Syndrome, IRIS) can develop.
Immune Reconstitution Inflammatory Syndrome (IRIS)
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.
Manifestations may include:
- Vasodilated shock
- Fevers and rigors
- Worsening of progressive multifocal leukoencephalopathy
- Worsening of CNS tuberculosis infection (or pulmonary, for that matter)
- Worsening of CMV retinitis
- Exacerbation (or de novo emergeance) of VZV encephalitis
- Worsening of cryptococcal meningitis
Freakish side-effects of antiretroviral therapy
These drugs are far from benign:
- All of them are hepatotoxic
- Didanosine and stavudine cause pancreatitis
- NRTIs cause lactic acidosis
- Tenofovir and indinavir are nephrotoxic
- Nevirapine causes Stevens-Johnson syndrome
- Prophylactic co-trimoxazole if the CD count is less than 200
- IV co-trimoxazole or pentamidine
- Steroid therapy and lung-protective ventilation for PJ pneumonia
Cryptococcus neoformans meningitis:
- Neck stiffness is often minimal or absent
- Test for cyptococcal antigen
- IV amphotericin plus flucytosine, followed by suppressive fluconazole
- Characteristic ring-enhancing lesions on CT
- Serology (toxoplasma antibodies) is always present
- Oral pyrimethamine, together with either intravenous sulfadiazine or clindamycin
Differential diagnosis of a space occupying intracranial lesion in a patient with advanced HIV:
- Primary CNS lymphoma (EBV antigen)
- Bacterial brain abscess
- Cryptococcal brain abscess
A systematic approach to the complications of HIV in an ICU patient
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.
- Intubation can be problematic, owing to the increased risk of VAP.
- Compared to patients with normal CD counts, patients with a CD count under 200 have a significantly higher mortality associated with invasive ventilation, and end up ventilated for much longer, which has led some authors to suggest that they should not be offered intubation.
- Consider unusual pathogens as the cause of pneumonia (eg.Pneumocystis, Mycobacterium avium complex, tuberculosis)
- Use lung-protective ventilation
- Dilated cardiomyopathy may be present ( a late complication of AIDS)
- Acute coronary syndromes are much more common among AIDS patients
- Autoimmune vasculitis affecting the coronaries is also common
- Autonomic neuropathy may be present, complicating their shock state
Central Nervous System problems
- Delirium in these patients is common
- Meningitis (especially with Cryptococcus) may not present with meningism
- Consider the following differentials for CNS disease:
- Viral (herpes) meningitis
- Subacute encephalitis
- Herpes simplex encephalitis
- Multifocal leukoencephalopathy
- HIV-related dementia and neurocognitive impairment.
Endocrine and electrolyte derangement
- Lactic acidosis may be due to NRTIs rather than shock
- Hyperlipidaemia and insulin resistance develop as a result of antiretroviral therapy
- The cortisol levels may be abnormally high; conversely they may be hypoadrenal.
- Electrolytes may be wildly deranged due to chronic diarrhoea
- Refeeding syndrome may occur due to premorbid malnutrition
- Involvement of renal system may be due to:
- Nephrotoxic effects of anti-retroviral drugs causing acute renal failure
- Chronic effects of HIV infection leading to end stage renal disease.
- Autonomic neuropathy may contribute to ileus and slow gastric emptying
- Oesophageal candidiasis results in an increased risk of bleeding from even minor oesophageal instrumentation
- Chronic diarrhoea due to CMV or Cryptosporidium may be present.
- Bowel perforation occurs more easily due to chronic colitis
- Either as a result of infection or as a consequence of antiretroviral therapy, these patients may have a host of haematological abnormalities:
- Viral load tends to increase in HIV patients receiving blood transfusion (due to transfusion-associated immunomodulation) and they should be transfused sparingly.