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UPDATE: Intensive Care Society (ICS) and British HIV Association (BHIVA) statement on considerations for critical care for people with HIV during COVID-19

Wednesday 23 December 2020

Overview

Individual Trusts and STPs have set up their own Clinical Support Units/Ethics committees who may advise on decisions around escalation of care in patients with COVID-19. These will vary according to local capacity.

NICE has produced a COVID-19 rapid guideline for critical care in adults https://www.nice.org.uk/guidance/NG159 recommending the use of the Clinical Frailty Score (CFS), acknowledging its limitations as the sole assessment of frailty, particular limitations in some groups, and the need to consider comorbidities and underlying health conditions in all cases.

In addition, there are some important issues related to antiretroviral therapy (ART) and steroid use for acutely unwell patients with HIV.

HIV testing is an important part of the diagnostic work-up for all people admitted with acute respiratory illness. Routine diagnostic testing for HIV is indicated on the basis of the clinical presentation only. Testing should not be omitted in cases with an absence of indicators associated with groups with higher prevalence of HIV infection.

The following recommendations aim to support appropriate decision-making around escalation of care for people with HIV and safe maintenance of HIV therapy, including common pitfalls.


Summary

1. People with well-controlled HIV have a normal life expectancy.

2. In the UK 97% of people diagnosed with HIV are on ART and 97% of this group are fully suppressed (ie well controlled.)

3. Some studies suggest that COVID-19 mortality may be higher in people with HIV although the determinants remain to be defined and confounding is possible. There is no indication at present that the management of people with HIV should be modified based on these initial observations [1,2].

4. Patients with well controlled HIV have similar intensive care outcomes to HIV-negative individuals [4].

5. HIV is not a predictor of mortality in people with acute lung injury admitted to intensive care [5].

6. COVID-19 may be associated with significant T-cell reduction, including CD4 cell count, in all patients [6,7].

7. People with HIV should receive COVID-19 treatments in line with local and national policies and these should not be delayed by potential interactions with HIV drugs.


Recommendations

1. Well-controlled HIV should not be included as a prognostic indicator when assessing appropriateness for escalation of care.

2. All patients with HIV should be discussed with an HIV team if possible, including a specialist HIV pharmacist.

3. COVID-19 may be associated with significant CD4 decline [6,7] so CD4 should be checked in all patients with HIV hospitalised with COVID-19 and appropriate prophylaxis commenced if necessary in line with national guidance [8].

4. HIV treatment should not be interrupted, even in the event of deterioration; ART can be switched in the setting of acute kidney injury, haemofiltration and dialysis in liaison with the local HIV team [9].

5. Several antiretrovirals inhibit tubular secretion of creatinine which may result in underestimation of GFR using creatinine-based methods; as a consequence, people may be labelled erroneously as having chronic kidney disease. Please consult with the HIV team regarding baseline renal function.

6. Atazanavir is normally associated with unconjugated hyperbilirubinaemia which is of no clinical consequence.

7. Several antiretrovirals, especially ritonavir and cobicistat, are associated with potentially serious drug-drug interactions; the University of Liverpool interaction checker is an invaluable resource [10]:

a. Significant increase in plasma concentration of drugs metabolised by the cytochrome P450 pathway including most steroids (including nebulised), anti-arrhythmics and simvastatin.

b. Significant reductions in antiretroviral concentrations risking virological rebound and drug resistance eg proton pump inhibitors.

8. Some antiretrovirals must be dosed with food [11].

9. Some antiretrovirals are available as liquid formulations or can be crushed for administration via NG tube [12].

10. Steroids for people with HIV admitted with COVID-19:

  • There are potential interactions between corticosteroids and HIV drugs but these should not delay corticosteroid administration and are of secondary importance.

  • We advise treating people with HIV as per local and national COVID protocols. Always initiate COVID treatment before seeking advice from local HIV teams.

  • Impact of HIV drugs on corticosteroid exposure:

- Dexamethasone and hydrocortisone exposure may increase with the antiretroviral boosters ritonavir and cobicistat – this is not considered clinically significant for corticosteroid courses less than 14 days but additional monitoring for adverse effects from higher exposure (Cushing’s +/- adrenal suppression) may be required.

- Dexamethasone and hydrocortisone exposure may decrease with efavirenz, nevirapine and etravirine – this is not considered clinically significant but increasing the corticosteroid dose may be considered.

  • Impact of corticosteroids on HIV drugs exposure

- Hydrocortisone has no predicted impact on HIV drug concentrations, so this is the preferred corticosteroid if clinically appropriate [13].

- Dexamethasone is a CYP3A4 inducer, so this may reduce concentrations of some HIV drugs:

- Rilpivirine-based regimens (Edurant, Eviplera, Odefsey and Juluca) should be switched or intensified (e.g. with raltegravir 400mg BD or dolutegravir 50mg OD) in liaison with the local HIV team.

- Doravirine dose should be doubled to 100mg BD in liaison with the local HIV team.

- Consider keeping HIV drug amendments in place for 2 weeks after stopping dexamethasone for courses of 7 days or more in liaison with the local HIV team.

  • HIV monitoring

- All patients admitted with COVID-19 should have a viral load measurement within 2-4 weeks of discharge to permit prompt diagnosis of virological failure.

Please see https://www.hiv-druginteractions.org/checker for more advice on drug-drug interactions or contact the specialist HIV pharmacist.


References

1. Geretti AM, Stockdale AJ, Kelly SH et al. Outcomes of COVID-19 related hospitalization among people with HIV in the ISARIC WHO Clinical Characterization Protocol (UK): a prospective observational study. Clin Infect Dis. 2020 Oct 23;ciaa1605.

2. Bhaskaran K, Rentsch CT, MacKenna B et al. HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. Lancet HIV. 2020 Dec 11;S2352-3018(20)30305-2.

3. BHIVA/EACS statement: https://www.bhiva.org/joint-EACS-BHIVA-statement-on-risk-of-coronavirus-for-PLWH

4. Barbier F et al. Intensive Care Med. 2020; 46(2): 329–342.

5. Mendez Tellez PA et al. Critical Care Medicine: July 2010 - Volume 38 - Issue 7 - p 1530-1535

6. Qin C, Zhou L, Hu Z et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clinical Infectious Diseases, ciaa248, https://doi.org/10.1093/cid/ciaa248

7. Diao B, Wang C, Tan Y et al. Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19). doi: https://doi.org/10.1101/2020.02.18.20024364

8. British HIV Association and British Infection Association Guidelines for the Treatment of Opportunistic Infection in HIV-seropositive Individuals 2011 https://www.bhiva.org/file/SwhaEzgXmAGOt/hiv_v12_is2_Iss2Press_Text.pdf

9. https://liverpool-hiv-hep.s3.amazonaws.com/prescribing_resources/pdfs/000/000/095/original/Renal_non- ARVs_2019_Jul.pdf?1562766072

10. https://www.hiv-druginteractions.org/

11. https://liverpool-hiv-hep.s3.amazonaws.com/prescribing_resources/pdfs/000/000/037/original/Food_ARVs_2019_Jul.pdf?1563973044

12. https://liverpool-hiv-hep.s3.amazonaws.com/prescribing_resources/pdfs/000/000/011/original/ARV_Swallowing_2018_Dec.pdf?154391 6096

13. https://www.nice.org.uk/guidance/ng159/resources/covid19-prescribing-briefing-corticosteroids-pdf-8839913581


For further information, email bhiva@bhiva.org or for media enquiries: Jo Josh, Communications Officer, British HIV Association (BHIVA) +44 (0) 7306 391875 or jo@commsbiz.com. For critical care information or media requests contact: Alex Day, Communications Manager, Intensive Care Society on +44 (0) 20 7280 4350 or alexd@ics.ac.uk.