BJA Education, xxx(xxx): xxx (xxxx)

doi: 10.1016/j.bjae.2023.03.004
Advance Access Publication Date: XXX

Matrix codes: 1A02,

2C01, 3C00

Update on the management of patients with HIV

infection in anaesthesia and critical care
D. Burtle1, S. Marsh2,* and N. Matin3
1
Leeds Teaching Hospitals NHS Trust, Leeds, UK, 2Harrogate District Hospital, Harrogate, UK and 3Barts
Health NHS Trust, Royal London Hospital, London, UK
*Corresponding author: [email protected]

Keywords: anaesthesia; critical care; HIV; immunodeficiency

Learning objectives Key points

By reading this article, you should be able to:
The majority of admissions to critical care for

Describe the common presentations of patients patients with controlled HIV are for conditions
with human immunodeficiency virus (HIV) unrelated to acquired immune deficiency syn-
requiring admission to critical care. drome (AIDS) such as bacterial infections and

Detail how combination antiretroviral treatment exacerbations of other comorbidities.
(cART) has changed the demographic of people
The incidence of classical AIDS-defining oppor-
with HIV in high-resource settings and the sub- tunistic infections is declining.
sequent medical issues they develop.
Acute respiratory failure, neurological conditions

Recall the practical issues concerning the man- and sepsis remain the most common causes of
agement of cART in patients with HIV presenting admission to critical care in HIV-positive
to critical care or for surgery. patients.

Discuss the perioperative considerations for
Combination antiretroviral treatment has revo-
those with HIV presenting for surgery. lutionised the care of patients with HIV, with
improved outcomes in in critical care.

Routine HIV antibody testing should be consid-
ered in all patients admitted acutely to hospital or
to critical care.

David Burtle FRCA FFICM is a specialty registrar in anaesthesia and The worldwide human immunodeficiency virus/acquired im-
intensive care medicine at Leeds Teaching Hospitals. He has previ- mune deficiency syndrome (HIV/AIDS) pandemic began to be
ously worked in HIV services in Africa and has published work on recognised in 1980 when a number of young men in the USA
HIV treatment programmes in conjunction with the University of started to develop opportunistic infections (OIs), which in many
Leeds. cases were fatal. The virus itself was subsequently identified in
1983 in Paris and its association with AIDS confirmed over the
Sarah Marsh FRCA FFICM is a consultant in anaesthesia and following years. Since its discovery 40 yrs ago, more than 32
intensive care medicine and the faculty tutor at Harrogate District million people have died as a result of HIV and AIDS.1
Hospital. She is the director of the examination preparatory course The management of HIV has been revolutionised over the
and chair of the Education Subcommittee at the FICM. past 25 yrs by effective testing programmes, public health
campaigns and antiretroviral treatment. Early detection and
Nashaba Matin FRCP is a consultant physician specialising in HIV
prompt, effective treatment of the condition has led to a
at Barts Health NHS Trust and is a postgraduate examiner for the
reduction in transmission in many at-risk populations, in
diploma in HIV medicine and the MRCP. She has worked extensively
addition to extending life in those infected. Patients with HIV
overseas, setting up an inpatient HIV unit in Bangladesh and
can now expect to have a normal life expectancy.1,2
advising on clinical issues related to HIV in Zambia.

Accepted: 1 March 2023

© 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: [email protected]

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
Management of HIV patients in anaesthesia and critical care

This review aims to provide an update on the management infection becomes chronic, there is a progressive decrease in
of HIV in adults to reflect the changes in detection, manage- CD4þ T-cell counts over a period of years. A CD4þ count <350
ment and outcome of patients with this disease.3 The care of cells mm3 defines a late diagnosis of HIV and is associated
pregnant women with HIV is beyond the scope of this article with an eight-fold increase in risk of death. As a result of more
and will be discussed in a forthcoming article in this journal. widespread HIV testing and surveillance in the UK, the num-
ber of late diagnoses is now declining (1861 in 2015 to 1279 in
2019).6
The course of HIV infection The risk of developing an AIDS-defining illness occurs with
HIV is a retrovirus that carries a reverse transcriptase enzyme a CD4þ count <200 cells mm3. The time frame over which the
allowing it to be incorporated into a host’s DNA. Transmission CD4þ count declines is variable, but has a median time frame
occurs through several mechanisms including sexual inter- of 8e10 yrs after seroconversion. Without treatment, HIV
course, mother to child (during pregnancy, birth and breast infection almost always leads to end-stage AIDS with recur-
milk) and through the mixing of blood. The virus preferen- rent OIs and death. Treatment with cART results in rapid
tially affects T-helper lymphocytes (CD4þ T cells) and gradu- control of HIV replication and a consequent recovery in CD4þ
ally destroys them in the host, leading to immune system count. Treatment failure with modern cART is uncommon
compromise and ultimately the development of AIDS. There and usually reflects problems with compliance. In an outpa-
are two variants of HIV: HIV-1 and HIV-2. HIV-1 is the most tient setting, the aim is to initiate cART as soon as possible,
prevalent worldwide, affecting up to 95% of those with HIV. ideally within 2 weeks of diagnosis. Successful HIV treatment
HIV-2 is predominantly confined to West Africa; it tends to can result in full suppression of the virus (undetectable viral
develop more slowly and be less transmissible than HIV-1. load) and means that it cannot be passed on during sexual
HIV-2 seldom causes critical illness and will not be dis- contact. This is a concept known as ‘undetectable equals
cussed further in this article. untransmittable’.7
After infection, acute seroconversion occurs with a rapid Although control of HIV through cART is remarkably
increase in the HIV viral load and a subsequent transient effective, several other factors affect the health of patients
decrease in CD4 count. This manifests in clinical practice as a with HIV. There is an increased risk of the development of
non-specific illness of fever, myalgia, rash and lymphade- chronic diseases such as atherosclerosis, ischaemic heart
nopathy (Fig. 1) and can mimic acute EpsteineBarr Virus (EBV) disease, chronic obstructive pulmonary disease, malignancy
infection.4 Acute seroconversion can lead to more serious (other than those associated with HIV), renal and hepatic
conditions such as acute HIV encephalitis, myocarditis or failure.8e10 Postulated theories for the development of these
acute respiratory failure, but this is rare.5 conditions include chronic low-level inflammation from HIV
The acute infection is followed by a plateau in viraemia or other opportunistic viruses, a concomitant increase in
with the formation of host anti-HIV antibodies. As the environmental exposure to tobacco or intravenous drug use,

Acute HIV syndrome

Primary Death
1200 wide dissemination of virus 107
infection
seeding of lymphoid organs
1100
CD4+ T lymphocyte count (cells mm–3)

1000 Opportunistic
106
HIV RNA copies per ml plasma
Clinical latency diseases
900
800
Constitutional
700 105
symptoms
600
500
104
400
300
103
200
100
0 102
0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11
Weeks Years

Fig 1 Temporal changes in plasma CD4þ lymphocyte count and plasma HIV RNA.4 Reproduced with permission.

2 BJA Education - Volume xxx, Number xxx, xxxx

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 Management of HIV patients in anaesthesia and critical care

and toxicity associated with some of the older antiretroviral bacterial sepsis.9,16 Patients with HIV are more susceptible to
drugs such as zidovudine.11 This has resulted in an increasing bacterial infection as compared with the general population;
incidence of critical care presentations for non-AIDS-related, this is true at all stages of immunocompetence.5 Although
HIV-associated conditions.5,12 bacterial pneumonia and meningitis are most common, skin,
soft tissue and haematogenous infections may also occur. The
management of sepsis should follow international guidelines,
Shifting epidemiology and sepsis in these patients does not result in a difference in
Globally there are 37.7 million people living with HIV, with 1.5 serological markers of infection compared with seronegative
million new infections per year.13 Significant progress has patients.9 Drug-resistant organisms are seen more commonly
been made after the ‘90e90e90’ target set by the United Na- in those with HIV, reflecting recurrent courses of antibiotics in
tions in 2016 e to diagnose 90% of all HIV-positive people, to the community and regular contact with healthcare services.
provide cART for 90% of all those diagnosed, and to achieve Haemophagocytic lymphohistiocytosis (HLH) can present
viral suppression for 90% of those treated by 2020. Although in patients with HIV, with a syndrome of recurrent febrile
this target was achieved in the UK in 2018, it remains a chal- episodes and associated cytopenia, mimicking sepsis. Hae-
lenge to do so for many other countries because of inequity of mophagocytic lymphohistiocytosis and its management has
access to testing facilities and availability of cART.14 been discussed previously in this journal; management is the
Attention in the UK has now turned to strategies that aim same for patients with HIV.17 Common triggers for HLH that
to end new HIV infections by 2030 with combination preven- must be excluded are underlying undiagnosed tuberculosis or
tion, strengthened HIV care (including early initiation of an occult malignancy such as lymphoma.
cART), improved partner notification of those newly diag-
nosed with HIV, widespread availability of HIV prophylaxis Respiratory infections
before exposure, and prevention services for people who Infections are the most common cause of acute respiratory
inject drugs. Routine HIV testing for people accessing acute failure in the HIV-positive patient with community-acquired
care and sexual health services is now also recommended.6 pneumonia, TB and Pneumocystis jirovecii pneumonia (PCP)
Globally there is significant variation in the composition of seen most frequently. When assessing an HIV-positive patient
HIV-positive populations. In 2020, 65% of UK HIV infections with acute respiratory failure, their immune status and his-
were in the following groups: sex workers and their clients, tory of and prophylaxis for OIs should be ascertained. The
men who have sex with men, people who inject drugs, presence of extrapulmonary features should be actively
transgender people and the sexual partners of the above sought (in particular for suspected TB infection) and relevant
groups. In high-income countries, HIV infection is now diag- microbiology results reviewed.
nosed disproportionally in groups from more disadvantaged Community-acquired pneumonia is the cause of up to 50%
backgrounds. This is reflected in admissions to critical care, of cases of acute respiratory failure (ARF), with Streptococcus
with cases of late-stage HIV infection occurring commonly in pneumoniae being the most common organism. Pseudomonas
migrant populations and those with barriers to accessing aeruginosa infection should also be considered as it can cause
healthcare.5 The success of cART has also produced a shift severe disease and may require deviation from local guide-
towards an ageing population of HIV-positive patients lines for antipseudomonal cover. With declining immuno-
accessing healthcare in high-income settings. competence, unusual or atypical bacterial pathogens
including Legionella pneumophila and Enterobacter spp. should
also be considered when choosing antimicrobial therapy. In
Admission to critical care those that are severely immunocompromised (CD4 count
Over the past 20 yrs, an improvement in survival of critical <350 cells mm3), haematogenous spread and pleuritis can
illness in patients with HIV has occurred as a result of both complicate bacterial pneumonia.18
improved treatment of HIV and general improvement in Pulmonary TB is responsible for ARF in up to 20% of pa-
critical care practices.9,15 Centralisation of care to specialist tients who are HIV-positive. It typically presents with cavi-
units is recommended where possible, and transfer of unwell tating lesions in the lung apices, but in the severely
patients with HIV from peripheral sites to a specialist centre is immunocompromised it can present atypically with more
advised. diffuse or miliary patterns (Fig. 2), and in extrapulmonary sites
In high-income settings, the type of presentation to critical including central nervous system, cutaneous and lymph
care in patients with HIV infection has changed, resulting in: nodes. Diagnosis is with sputum acid-fast bacilli (AFB) and
culture and polymerase chain reaction (PCR) for mycobacte-
(i) A decreasing incidence of patients admitted with ill-
rium. Treatment of susceptible TB is with standard combi-
nesses and opportunistic infections (now fewer than 30%
nation antibiotic therapy (rifampicin, isoniazid, ethambutol
of admissions).1
and pyrazinamide) for 6e12 months.9
(ii) An increasing incidence of patients admitted with
P. jirovecii pneumonia is a classic AIDS-defining condition
comorbidities accelerated by HIV and cART.
causing up to 20% of cases of ARF in HIV-positive patients. It is
(iii) Challenges in managing cART during both HIV-related
declining as a cause for critical care admission but remains
illness and unrelated conditions; more than 70% of pa-
common in those with previously unknown HIV infection.16 It
tients admitted to critical care with HIV are taking cART.7
presents with a triad of worsening dyspnoea, dry cough and
high fever over a period of weeks and can progress rapidly to
respiratory failure. Classical descriptions suggest that it
Disease presentation
should lack the haemodynamic instability that may be pre-
The most common reasons for admission of patients with HIV sent in sepsis from bacterial pneumonia, and that haemody-
to critical care are similar to those in seronegative patients: namic instability should prompt a search for an alternative or
acute respiratory failure, reduced conscious level and concomitant pathogen. The typical radiological features seen

BJA Education - Volume xxx, Number xxx, xxxx 3

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
Management of HIV patients in anaesthesia and critical care

staining, or by PCR. A 3-week course of cotrimoxazole is the

first line treatment. In moderate to severe PCP (PaO2 9.3 kPa [70
mmHg] or SpO2 92%), adjuvant steroid treatment (e.g. pred-
nisolone 40 mg twice daily) started within 72 h of treatment
has a proven mortality benefit and reduces the duration of
mechanical ventilation.18 There is a high risk of pneumo-
thorax in those with severe PCP and a high index of suspicion
is needed in the event of an acute clinical deterioration.
Extracorporeal membrane oxygenation (ECMO) has been used
for severe respiratory failure in patients with HIV and as such
a diagnosis of HIV should not exclude a referral for consider-
ation of ECMO.9
COVID-19 infection has been associated with poor out-
comes in those with low CD4þ counts or a detectable viral
load in some studies.19 In patients with controlled HIV, mor-
tality rates are similar to those without HIV. Any potential
interactions with HIV drugs must be reviewed and should not
delay initiation of COVID-19 treatments. All patients admitted
to hospital with COVID-19 infection should have an HIV test as
part of their routine assessment. Clinical signs and symptoms
of COVID pneumonitis can mimic PCP pneumonia.
There are a number of other uncommon mycobacterial,
viral and fungal causes of ARF (listed in Fig. 3). These pre-
dominantly occur in those with CD4þ counts <100 cells ml1.
Fig 2 Chest X-ray showing miliary TB.

Neurological disease and HIV

include diffuse bilateral alveolar consolidation that spares An acute neurological deterioration in a patient with HIV
peripheral zones and ground glass changes. Diagnosis is by should prompt a thorough investigation with early contrast
bronchoalveolar lavage (BAL) for immunofluorescence or enhanced imaging (MRI superior to CT) and CSF analysis, in

Admission for ARF Admission for neurological disorders

Acute HlV encephalitis

Acute HlV infection
(highly uncommon)

Common pulmonary OI: PCP Common CNS OI: toxoplasmosis,

CD4 <200-250/µL
Rare pulmonary OI: KS, CMV, tuberculosis, cryptococcosis
(inaugural admission,
toxoplasmosis, MAC, nocardiosis, Rare CNS OI: CMV, nocardiosis,
cART-naϊve patients, cART
aspergillosis, rhodococcosis, aspergillosis, PML, HIV encephalitis,
procurement issues)
histoplasmosis, cryptococcosis NHL, neurosyphilis

IRIS Recent cART initiation IRIS

Bacterial pneumonia, tuberculosis 1 All stages of HIV infection Bacterial meningitis (S. pneumoniae)

Stroke, epilepsy, noninfectious

COPD, bronchiectasis, lung cancer, CD4 >200-250/µL
encephalitis, bacterial brain abscess,
pulmonary hypertension, lung fibrosis (cART-treated patients
systemic diseases with CNS
heart failure, non-HIV-related diseases 2 ageing with comorbidities)
involvement 3

Fig 3 Potential differential diagnoses for patients who develop acute respiratory failure or neurological compromise using patient’s CD4þ count and state of
immunocompetence.9 Reproduced with permission. ARF, acute respiratory failure; cART, combination antiretroviral therapy; IRIS, immune reconstitution in-
flammatory syndrome; KS, Kaposi sarcoma; MAC, Mycobacterium avium complex; NHL, non-Hodgkin lymphoma; OI, opportunistic infection; PCP, Pneumocystis
jirovecii pneumonia; PML, progressive multifocal encephalopathy (JC virus encephalitis). (1) Pulmonary tuberculosis is also a major cause of IRIS that may lead to
ARF; (2) interstitial pneumonitis, drug toxicity, asthma, pulmonary embolism, others; (3) sepsis, endocarditis, anoxia, metabolic disorders, drug toxicity or
overdose, malignancies, thrombotic microangiopathy, other.

4 BJA Education - Volume xxx, Number xxx, xxxx

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 Management of HIV patients in anaesthesia and critical care

addition to a careful history and clinical examination. There worsening headache, seizures, visual symptoms and a pro-
are multiple potential infectious causes (Fig. 3), of which TB gressive cognitive deficit. MRI of the brain may reveal char-
meningitis, cerebral toxoplasmosis and cryptococcal menin- acteristic encephalitis, hydrocephalus and/or signs of raised
gitis are the most common. It is possible that multiple OIs may intracranial pressure. Cerebrospinal fluid analysis typically
coexist and careful attention to the clinical signs and symp- shows lymphocytosis, a moderate protein increase and
toms is required. normal glucose concentration. Other investigations include
TB meningitis causes fever, focal neurological deficits, India ink staining for cryptococcus and a CSF cryptococcal
progressive cognitive decline and new-onset seizures. Imag- antigen test. Cryptococcus neoformans yeast may also be
ing may reveal meningeal inflammation, evidence of tuber- cultured from CSF. If CSF analysis is not possible or is delayed,
culomas or hydrocephalus (Fig. 4). A characteristic CSF result a positive serum blood cryptococcal antigen test can be a
would show lymphocytosis, low glucose and increased pro- useful diagnostic indicator alone. Treatment is with i.v. anti-
tein. Treatment is as per national guidelines with four or more fungal therapy (ambisome and flucytosine) for at least 8
CNS penetrating drugs along with adjuvant steroid therapy.5 weeks. Regular assessment and management of raised intra-
There are significant drug interactions between cART and cranial pressure is essential in patients with cryptococcal
antituberculous therapy; this should be managed jointly by meningitis; this may require daily lumbar punctures or
both infectious disease and HIV specialists. insertion of a VP shunt. Intracranial pressure should be
Cerebral toxoplasmosis classically presents with motor measured at the initial lumbar puncture with early referral to
deficit, altered cognition and seizures. It results from reac- the neurosurgical team if raised.
tivated Toxoplasmosis gondii cysts and has characteristic im- Cytomegalovirus (CMV) reactivation is seen in severely
aging findings on MRI of multifocal ring enhancing lesions in immunocompromised patients with HIV (CD4 count <50 cells
the cortex and basal ganglia with marked cerebral oedema mm3). It can result in multisystem involvement including
(Fig. 5). Diagnosis is primarily based on the clinical history in retinitis, colitis and oesophageal ulceration, and neurological
those with a low CD4þ count and positive findings on MRI. It and respiratory compromise. Patients may present with ody-
can be aided by PCR for T. gondii on CSF sampling and a pos- nophagia or diarrhoea caused by gastrointestinal involve-
itive IgG test. However, a negative CSF sample does not ment. Blood PCR or biopsy evidence of CMV can confirm the
exclude the diagnosis. Treatment is with a combination of diagnosis. Treatment is with intravenous ganciclovir, oral
pyrimethamine and sulfadiazine for up to 6 weeks, with reg- valganciclovir, or both.
ular clinical and radiological review to monitor treatment
response. An MRI should be repeated at 2 weeks to review Malignancy and HIV
progress. If there is no response, then an alternative diagnosis Advancements in treatment for malignancies associated with
must be sought such as central nervous system TB or primary HIV infection have resulted in improved outcomes. Admission
cerebral lymphoma (brain biopsy potentially needed). to critical care may occasionally be required for issues relating
Cryptococcal meningitis is a low-grade, indolent fungal to treatments such as chemotherapy-induced tumour lysis
meningitis and presents differently to an acute bacterial syndrome, neutropenic sepsis, or because of complications of
meningitis. It is suspected in the context of low-grade fever, the malignancy itself.
Non-Hodgkin’s and Hodgkin’s lymphomas are seen in both
those with suppressed virus and the immunocompromised,
often associated with EBV infection. Critical care admissions
may be required because of cytopenias, neurological deficits
or consequences of treatment.
Kaposi sarcoma is an endothelial tumour associated with
human herpes virus 8 (HHV8); it can cause multisystem ef-
fects including classical skin lesions, intestinal bleeding and
respiratory tract obstruction. Immune restoration via cART is
the mainstay of treatment although adjuvant chemotherapy
may also be required. With early diagnosis the prognosis is
good.
Castleman disease is a B-cell lymphoproliferative condi-
tion resulting from HHV8 infection that produces a severe
systemic hyperinflammatory response similar to HLH. This
can be challenging to diagnose and difficult to distinguish
from severe sepsis. A tissue diagnosis is required from an
affected node. Outcomes from this were historically poor but
have improved with newer monoclonal antibody therapies.

Patients with unknown HIV status admitted to critical

care
Immunosuppression associated with HIV may present in a
variety of ways and may mimic other illnesses. In view of this,
HIV testing should be considered as a routine investigation in
the critically ill, regardless of clinical presentation, age, risk
Fig 4 MRI of head showing cerebral tuberculomas. factors or prior HIV-negative test results. Historical guidance
on pretest counselling for patients before HIV testing are no

BJA Education - Volume xxx, Number xxx, xxxx 5

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
Management of HIV patients in anaesthesia and critical care

(iii) Protease inhibitors (PI) (e.g. darunavir): inhibit the cleavage

of viral polyproteins and the production of new virus.
(iv) Integrase inhibitors (e.g. dolutegravir): bind to the inte-
grase enzyme and prevent incorporation of viral DNA
into CD4þ cell nucleic DNA.

Combination antiretroviral treatment regimens involve

two to three drug classes used in combination to reduce viral
resistance and improve treatment efficacy. Prescribing is
based on genotypic resistance of the virus to assess suscep-
tibility to available HIV drugs while balancing the side effect
profiles and drug interactions with co-prescribed medica-
tions. Tolerability and pill burden have improved over recent
years in part because of the availability of co-formulated
single-tablet regimens which can aid compliance.

Practicalities of using cART in critical care

Combination antiretroviral treatment medications should be
continued where possible in critical illness. However they can
only be given enterally, as i.v. formulations of cART drugs are
not available currently. This can present a problem in the
critically ill patient where variable enteral absorption may
occur. Existing regimens may need to be altered to drugs that
can be given via the nasogastric route and expert advice from
a pharmacist, with input from specialist HIV teams is advised.
Dose modification may also be required in patients with
impaired renal or hepatic function. Although interruptions in
therapy should be avoided, modern antiretroviral drugs have
Fig 5 MRI showing cerebral toxoplasmosis. a high genetic barrier to resistance resulting from in-
terruptions in therapy. In addition, the risk of resistance
resulting from interrupting treatment can be managed with
longer applicable in the context of what is a treatable and
relative ease upon recovery from critical illness.
manageable illness with a normal life expectancy.6
Several comprehensive resources are available to allow
clinicians to check interactions between cART and other
commonly used drugs in critical care and anaesthesia. In the
cART and critical illness UK, the University of Liverpool HIV drug interactions website
Historically, cART was only started once a patient’s CD4þ provides an excellent source for reference (www.hiv-
count had decreased below a certain threshold. This strategy druginteractions.org/checker).
has now been replaced by one of early initiation (within 2 Polypharmacy can present challenges and requires close
weeks of diagnosis). The British HIV Association (BHIVA) attention. Key drug interactions are frequent because of the
guidelines recommend commencement of treatment with metabolism of the drugs through hepatic cytochrome P450
cART upon diagnosis of HIV infection. This is associated with and glucuronidation pathways. Drug toxicity with cART can
a significant reduction in the risk of disease progression.20 The also occur (and may precipitate admission to critical care) but
use of cART therefore is now widespread. It is beneficial to has decreased with newer regimens; the discontinuation of
understand treatment so that it can be managed successfully older agents such as zidovudine has reduced the incidence of
if a patient receiving cART presents to critical care or requires adverse effects. Should a patient with HIV on cART present to
cART to be started during their admission. critical care with organ failure but without a clear precipitant,
the multisystem effects of cART should be considered and
specialist advice sought to modify HIV therapy as required.
Mechanisms of action of cART The decision to start cART in a patient newly diagnosed
with HIV is complex, and treatment is rarely commenced
Four classes of antiretroviral drugs are prescribed commonly
acutely during critical illness. The decision must be made in
for HIV. An understanding of their mechanism of action re-
conjunction with HIV specialists and after careful consider-
quires an appreciation of how HIV replicates in an infected
ation of the clinical situation. Before starting therapy, the
individual (Fig. 6).
patient’s condition must be relatively stable and any acute
(i) Nucleoside reverse transcriptase inhibitors (NRTI) (e.g. illnesses managed actively. Immune reconstitution inflam-
tenofovir, emtricitabine): cause interruption in the matory syndrome (IRIS) is a paradoxical worsening of a
transcription of viral RNA into DNA through insertion of treated or undiagnosed OI after the commencement of cART.
the drug into the DNA chain being transcribed. In order to reduce the risk of IRIS, it is important to manage
(ii) Non-nucleoside reverse transcriptase inhibitors (NNRTI) (e.g. and supress potential or active OIs before commencing cART.
doravirine, efavirenz): cause interruption in the tran- This occurs most often in patients with a high HIV viral load,
scription of viral RNA into DNA by a direct effect on low initial CD4þ count and rapid recovery in CD4þ count after
reverse transcriptase enzymes. starting HIV treatment.9 Management of IRIS is with steroids,

6 BJA Education - Volume xxx, Number xxx, xxxx

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 Management of HIV patients in anaesthesia and critical care

Fig 6 Human immunodeficiency virus infection of a CD4þ cell and the mechanisms of action of classes of cART drugs in the disruption of this process.20
Reproduced with permission. Infection starts with viral fusion to the CD4þ cell membrane, which is facilitated by HIV surface proteins and CD4þ membrane
proteins. Human immunodeficiency virus viral RNA then undergoes reverse transcription. Resulting double stranded DNA is incorporated into the CD4þ nucleic
DNA, which is facilitated by integrase enzymes. A proportion of CD4þ cells with incorporated viral DNA remain dormant, do not replicate viral DNA and are
resistant to immune response and cART action. However, a proportion of CD4þ cells undergo DNA transcription via RNA polymerase producing new viral RNA and
viral mRNA. Viral mRNA is then translated into viral polyprotein before being cleaved by HIV proteases and packaged into HIV virions that bud and are released
into the host circulation.

while continuing cART if this is safe to do so. Patients with arrest data are similar between seronegative and positive
intracranial OI such as TB, cryptococcus and toxoplasmosis groups. In patients with OIs such as PCP, TB and toxoplas-
are of particular concern because of the risk of neurological mosis, those with HIV have a better prognosis than those that
deterioration caused by worsening inflammation or increased are immunosuppressed for other reasons. Stage of HIV
ICP. The timing of starting cART in such patients varies, but infection, CD4þ count and viral load do not correlate well with
should be ideally within 2e4 weeks after starting treatment of short-term survival in critical care in those with respiratory
the OI, and if there is demonstrable control of the OI.21 failure, low GCS or sepsis and should not be used to
prognosticate.5,15

Outcomes
Outcome data for patients with HIV admitted to critical care in
Anaesthesia and perioperative management
high-income settings is largely similar to seronegative pa- There has been an increase in the number of patients with
tients when matched for disease severity, with mortality rates stable disease with improving treatment in those who are
similar for unselected patients (between 16% and 35%).5,9 HIV-positive. There are an estimated 101 200 patients with
Acute respiratory distress syndrome (ARDS) and cardiac stable HIV disease in the UK at present.7 Increased prevalence

BJA Education - Volume xxx, Number xxx, xxxx 7

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
Management of HIV patients in anaesthesia and critical care

and higher rates of comorbid disease in this population has (ii) A sharps injury from someone with HIV on treatment
led to an increase in the number of patients requiring anaes- for more than 6 months with undetectable viral load
thetic care for issues not directly associated with HIV. may not require PEP (case-by-case basis).
The perioperative management of patients with HIV (iii) A splash injury from someone with HIV on treatment
should involve consideration of whether the patient has sta- more than 6 months with undetectable viral load does
ble disease, the current status of viral replication (controlled not require PEP.
or uncontrolled) and the presence of comorbid conditions. (iv) A high-risk injury from someone of unknown status but
Points to consider when assessing a patient for anaesthesia from a low-risk group does not require PEP.
include: (v) All efforts should be made to test the donor voluntarily
as soon as possible.
(i) Minimising the interruption of cART where possible.
(vi) Testing the donor should not delay starting PEP where
(ii) Assessing potential interactions between cART and
indicated.
agents used during anaesthesia.
(vii) If the donor is unable to give consent for testing, then
There are a significant number of potential interactions
HIV testing can be performed if it is in the best interest of
across multiple classes of drugs used in anaesthesia,
the donor.23
including propofol and ketamine. In modern antiretrovi-
ral treatment regimens, protease inhibitors cause the Decisions about PEP in individual cases must be done using
most interactions and a thorough assessment of drug clinician judgement taking into account the opinion of the
history and interactions must be completed before pro- person involved in the incident. Factors increasing risk
ceeding with anaesthesia. include characteristics of the donor, inoculum of blood and
(iii) Assessing comorbidities associated with HIV and the use historical virology results of the donor. In many cases the risk
of more toxic, historical cART agents. remains low. For example, in a hypothetical needlestick injury
(iv) Assessing the organ systems affected by disease in a from a man having sex with men in London, the probability of
patient with uncontrolled disease.22 the index case being HIV-positive with a detectable viral load
is 32/1000, which when multiplied by the transmission risk of
Preoperative assessment should consider the implications
1/333 gives a risk of HIV transmission of 32/10001/333¼32/
that the patient’s disease control and history have on the
333 000 or 0.01%.23 In many cases, the small risk of HIV
potential organ systems involved. The increased risk of
transmission should be balanced against the potential toxicity
atherosclerosis, ischaemic heart disease and cardiomyopa-
and inconvenience of PEP, meaning it may not be given.
thy, from both disease and treatments, should be considered.
PEP should be started as soon as possible and up to 72 h after
Targeted assessment of cardiovascular function and consid-
injury and continued for 28 days. A standard regimen is teno-
eration of formal structural and functional testing should be
fovir/emtrictabine (combined tablet) with raltegravir once daily.
performed if there are concerns identified. Assessment of
respiratory function should be guided by the stage of disease.
Although most respiratory sequelae are associated with Conclusions
advanced disease, chronic obstructive pulmonary disease can
The era of cART has dramatically changed HIV care and
be occult and its presence should be assessed for. The po-
resulted in an increase in life expectancy for those with HIV.
tential for renal failure requires the avoidance of nephrotoxic
This has led to a significant change in the type of critical care
drugs, dose adjustment of renally excreted drugs and opti-
presentation encountered in this cohort. Outcomes after
misation of fluid status.
critical care in those with HIV have improved dramatically.
Challenges for perioperative care reflect the changing profile
Accidental inoculation and post-exposure of patients with HIV. Human immunodeficiency virus anti-
body testing should be routine and should be a standard part
prophylaxis
of the assessment of all those admitted acutely to hospital and
Personal protective equipment guidelines should be followed critical care.
as for any other patient; no additional precautions are needed
for patients with HIV/AIDS including invasive surgery. The
risk of HIV infection via accidental inoculation from a nee- Declaration of interests
dlestick injury or blood spillage from a patient with unde- The authors declare that they have no conflicts of interest.
tectable viral load is extremely low. Even for those with
uncontrolled disease, the risk of transmission is only 0.3% and
0.1% for needlestick injury and blood splash, respectively.23 If MCQs
a healthcare worker is exposed, local guidelines should be The associated MCQs (to support CME/CPD activity) will be
available in all clinical settings. The cornerstones of this are accessible at www.bjaed.org/cme/home by subscribers to BJA
early assessment of the risk profile of the donor and the route Education.
of inoculation, presumption of high risk if information is un-
clear and early commencement of post-exposure prophylaxis
(PEP). References
The 2021 BHIVA guidelines reflect a move away from PEP
1. Fauci A, Lane C. Four Decades of HIV/AIDS d much
for injuries that may previously have required treatment.
accomplished, much to do. N Engl J Med 2020; 383: 1e4
They recommend.
2. May MT, Gompels M, Delpech V et al. Impact on life ex-
(i) A sharps injury or mucosal splash (high-risk injury) pectancy of HIV-1 positive individuals of CD4þ cell count
from someone with known uncontrolled HIV or on and viral load response to antiretroviral therapy. AIDS
treatment for less than 6 months requires PEP. 2014; 28: 1193e202

8 BJA Education - Volume xxx, Number xxx, xxxx

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 Management of HIV patients in anaesthesia and critical care

3. Prout J, Agarwal B. Anaesthesia and critical care for pa- 14. Levi J, Raymond A, Pozniak A et al. Can the UNAIDS
tients with HIV infection. Contin Educ Anaesth Crit Care Pain 90e90e90 target be achieved? A systematic analysis of
2005; 5: 153e6 national HIV treatment cascades. BMJ Global Health 2016;
4. Lewthwaite P, Wilkins E. Natural history of HIV/AIDS. 1, e000010
Medicine 2009; 37: 333e7 15. Dickson SJ, Batson S, Copas AJ, Edwards SG, Singer M,
5. Azoulay E, de Castro N, Barbier F. Critically ill patients Miller RF. Survival of HIV-infected patients in the inten-
with HIV 40 years later. Chest 2020; 157: 293e309 sive care unit in the era of highly active antiretroviral
6. British HIV Association/British Association for Sexual therapy. Thorax 2007; 62: 964e8
Health and HIV/British Infection Association. Adult HIV 16. Cilloniz C, Torres A, Polverino E et al. Community-ac-
testing guidelines 2020. Available from: https://www. quired lung respiratory infections in HIV-infected pa-
bhiva.org/file/5f68c0dd7aefb/HIV-testing-guidelines-2020. tients: microbial aetiology and outcome. Eur Respir J 2014;
pdf (accessed 31 January 2022). 43: 1698e708
7. Public Health England. HIV in the United Kingdom: to- 17. Bell A, Tattersall R, Wenham T. Rheumatological condi-
wards zero HIV transmissions by 2030. Available from: tions in critical care. BJA Educ 2016; 16: 427e33
https://assets.publishing.service.gov.uk/government/ 18. Ewald H, Raatz H, Boscacci R et al. Adjunctive corticoste-
uploads/system/uploads/attachment_data/file/965765/ roids for Pneumocystis jirovecii pneumonia in patients with
HIV_in_the_UK_2019_towards_zero_HIV_transmissions_ HIV infection. Cochrane Database Syst Rev 2015; 4:
by_2030.pdf (accessed 31 January 2022). CD006150
8. Akgun KM, Gordon K, Pisani M et al. Risk factors for 19. Brown LB, Spinelli MA, Gandhi M. The interplay between
hospitalization and medical intensive care unit (MICU) HIV and COVID-19: summary of the data and responses to
admission among HIV-infected Veterans. J Acquir Immune date. Curr Opin HIV AIDS 2021; 16: 63e73
Def Syndr 2013; 62: 52e9 20. Gandhi M, Gandhi RT. Single-pill combination regimens
9. Barbier F, Mer M, Szychowiak P et al. Management of HIV- for treatment of HIV-1 infection. N Engl J Med 2014; 371:
infected patients in the intensive care unit. Intensive Care 248e59
Med 2020; 46: 329e42 21. British HIV Association (BHIVA). BHIVA guidelines for the
10. Gutierrez J, Albuquerque ALA, Falzon L. HIV infection as treatment of HIV-1-positive adults with antiretroviral
vascular risk: a systematic review of the literature and therapy 2015 (2016 interim update). 2015. London
meta-analysis. PLoS One 2017; 12, e0176686 22. Wilson S. Anaesthesia and HIV. Updates in anaesthesia.
11. Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV Available from: https://e-safe-anaesthesia.org/e_library/
infection as a chronic disease. Lancet 2013; 382: 1525e33 11/HIV_and_anaesthesia_Update_2009.pdf. 2009. (accessed
12. Barbier F, Roux A, Canet E et al. Temporal trends in critical 1 December 2021).
events complicating HIV infection: 1999e2010 multicentre 23. British HIV Association/British Association for Sexual
cohort study in France. Intensive Care Med 2014; 40: 1906e15 Health and HIV/British Infection Association. PEP guide-
13. Global HIV & AIDS statistics d fact sheet. UNAIDS. lines 2020. Available from: https://www.bhiva.org/PEP-
Available from: https://www.unaids.org/en/resources/ guidelines (accessed 20 January 2022).
fact-sheet (accessed 21 November 2021).

BJA Education - Volume xxx, Number xxx, xxxx 9

Downloaded for Salvador Manuel Teran Morales ([email protected]) at R4L.Mongolia from ClinicalKey.com by
Elsevier on June 11, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.