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Emergencies in HIV-positive patients 

Emergencies in HIV-positive patients
Chapter:
Emergencies in HIV-positive patients
Author(s):

Punit S. Ramrakha

, Kevin P. Moore

, and Amir H. Sam

DOI:
10.1093/med/9780198797425.003.0008
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date: 13 August 2020

Emergency presentations of HIV infection

Patients with HIV infection may present with:

  • HIV-related or HIV-unrelated problems.

  • Toxicity related to anti-HIV therapy.

  • Primary HIV infection (PHI) (seroconversion).

It is important to recognize and diagnose HIV infection in individuals in whom this has been previously unrecognized, and identify patients who may have been exposed to HIV and who may need treatment.

Where there is local expertise in the management of HIV infection, it is recommended that care is provided in consultation with the appropriate team. It is essential to consult with specialists before prescribing any specific treatments.

General principles

  • The use of combination antiretroviral therapy is very successful. HIV is now considered to be a chronic manageable disease. Successful antiretroviral therapy significantly increases the CD4 count and reduces the risk of opportunistic complications. Highly active antiretroviral therapy (HAART) reduces HIV RNA load to undetectable levels (e.g. <20 copies/mL of plasma) in >95% of patients.

  • Patients with known or suspected HIV infection should be investigated and managed aggressively.

  • Unusual opportunistic infections and malignancies are more common and may occur simultaneously or sequentially.

  • Toxicity from antiretroviral therapy may present to acute medical services.

  • Drug interactions with antiretroviral therapy are common.

  • Common diseases still affect HIV-positive individuals but may present atypically.

  • All patients should have a full examination, including a careful examination for unusual rashes, skin lesions, and lymphadenopathy, as well as the mouth. Examination of the mouth can reveal a great deal of information regarding the level of immunity [e.g. oral thrush and hairy leukoplakia suggest Emergencies in HIV-positive patients immunity and risk of severe opportunistic infections; Kaposi’s sarcoma (KS) suggests Emergencies in HIV-positive patients risk of visceral KS].

  • Indicator diseases that should alert the clinician to investigate for HIV include TB, candidiasis, cryptococcosis, cryptosporidiosis, CMV infections, KS, and toxoplasmosis (see Table 8.1).

  • Always consider the possibility of HIV in patients from sub-Saharan Africa and men who have sex with men (MSM).

  • The acute physician may be the first to consider HIV in previously undiagnosed patients.

Table 8.1 Clinical indicator diseases for adult HIV infection

AIDS-defining conditions

Other conditions where HIV testing should be considered

Respiratory

  • TB

  • PCP

Bacterial pneumonia

Aspergillosis

Neurology

  • Cerebral toxoplasma

  • Primary cerebral lymphoma

  • Cryptococcal meinigitis

  • Progressive multifocal leukoencephalopathy (PML)

Aseptic meningitis/encephalitis

Cerebral abscess

Space lesion of unknown cause

GBS

Transverse myelitis

Dementia

Peripheral neuropathy

Dermatology

  • KS

Severe psoriasis

Severe seborrhoeic dermatitis

Multi-dermal zoster

Gastroenterology

  • Persistent cryptosporidiosis

Oral candidiasis

Oral hairy leukoplakia

Chronic diarrhoea (unknown cause)

Weight loss (unknown cause)

HBV or HCV infection

Salmonella, Shigella, or Campylobacter

Oncology

  • Non-Hodgkin’s lymphoma

Hodgkin’s lymphoma or Castleman’s

Anal cancer or dysplasia

Lung cancer

Seminoma

Head and neck cancer

Gynaecolgical

  • Cervical cancer

Cervical or vaginal dysplasia

Haematological

Any unexplained blood dyscrasia

Ophthalmological

  • CMV retinitis (see Fig. 8.2)

Any infective retinitis (zoster, Toxoplasma)

ENT

Lymphadenopathy (unknown cause)

Other

PUO or STI, mononucleosis-like syndrome

(See Box 8.1.)

HIV testing

In most situations, HIV testing is carried out with informed consent by genitourinary medicine (GUM)/sexually transmitted infection (STI) clinics, in primary care, or as part of routine antenatal care. However, the presentation of individuals with potentially HIV-related complications or at potential risk of previous HIV exposure to the emergency clinician provides an opportunity to diagnose the infection. While most choose to have an HIV test within the confidential setting of a specific HIV-testing service, any health-care provider should possess the essential skills for appropriate discussion of HIV testing. HIV testing should no longer be exceptional but should be considered with informed consent in all patients with clinical indicator diseases or presentations.

Pretest discussion

In-depth discussion is only necessary where there is a high probability of a positive result, otherwise a simple yes/no question may be appropriate. If the patient declines or has further questions, then it is important to dispel any misconceptions and detail the benefits of testing (specifically that early diagnosis has a better prognosis through access to treatment and that the disease, while currently incurable, has a good life expectancy, etc.). If the chance of a positive result is high, more detail about testing should be given prior to testing. The following issues should be included in a ‘pretest’ discussion:

  • Rationale for testing (see Box 8.2).

  • Benefits of knowing the status.

  • When and by whom the result will be given.

  • ‘Window period’ of infection (i.e. may take up to 8 weeks from exposure for an HIV antibody test to become positive).

  • Confidentiality: testing for HIV, and any result whether positive or negative, does not require disclosure to a GP. A positive result does not necessarily need to be disclosed to third parties without consent but will have implications for insurance/mortgages.

Post-test discussion

The following principles should be followed in a ‘post-test’ discussion:

  • Giving a positive result should follow the principles of breaking bad news.

  • If a result is positive, early referral to an HIV clinician is essential.

  • If a result is negative, the window period should be reinforced (particularly in situations where seroconversion is suspected; Emergencies in HIV-positive patients Primary HIV infection, p. [link]).

  • If a result is negative, the opportunity for future risk reduction should be considered.

HIV testing without consent

It is rarely necessary to test for HIV infection without consent. However, this is justified in the following settings:

  • Testing of organ transplantation donors.

  • Testing of the unconscious/confused patient where HIV infection is suspected and the management of the patient will be materially changed by knowledge of their HIV status.

  • Testing of the unconscious patient who is the ‘donor’ in a significant needle-stick/splash injury. In this situation, testing is justified if the patient is unlikely to regain consciousness for 48h but should only be performed on a blood specimen that has been previously taken for another purpose.

  • Given the potential litigation arising from HIV testing without consent, it is advisable to seek a second opinion (preferably from a physician with HIV experience) that such testing is justified.

Universal HIV testing is recommended in the following settings

  • GUM or sexual health clinics.

  • Antenatal services.

  • Termination of pregnancy services.

  • Drug dependency programmes.

  • Health-care services for those diagnosed with TB, viral hepatitis B or C, and lymphoma.

  • In areas of >2/1000 prevalence, routine screening for all new registrations with a GP and all medical admissions to hospital.

HIV testing should be routinely recommended to the following

  • All patients presenting for health care where HIV or HIV indicator diseases enter the differential diagnosis (see Table 8.1; Emergencies in HIV-positive patients Primary HIV infection, p. [link]).

  • All patients diagnosed with an STI.

  • All sexual partners of men and women known to be HIV-positive.

  • All men who have disclosed sexual contact with other men.

  • All ♀ sexual contacts of MSM.

  • All patients reporting a history of injecting drug use.

  • All men and women from a country of high HIV prevalence.

  • All men and women who report sexual contact abroad or in the UK with individuals from countries of high HIV prevalence.

Further information can be found at: Emergencies in HIV-positive patients https://www.bhiva.org/HIV-testing-guidelines

Primary HIV infection

PHI (also known as HIV seroconversion illness) is easily overlooked. Intervention may help prevent further spread of HIV (individuals recently infected with HIV are thought to be highly infectious, particularly if unaware of their status).

Risk of recent infection

A significant history of exposure to a potential HIV source within the last 3 months (sexual, percutaneous, or mucocutaneous), in conjunction with any of the features listed here, warrants performing specific diagnostic tests for PHI.

Symptoms and signs

  • Typically within 2–4 weeks of exposure but can be up to 3 months.

  • Flu-like illness (fever, myalgia, headache, lymphadenopathy, retro-orbital pain).

  • Maculopapular rash (differential diagnosis of secondary syphilis).

  • Pharyngitis/oral ulceration.

  • Concomitant STIs (e.g. primary or secondary syphilis, gonorrhoea, genital ulcer disease).

Laboratory findings

  • HIV antibody tests may be negative at the time of seroconversion, and an HIV RNA viral load test may be required to confirm the diagnosis.

  • Lymphopenia, thrombocytopenia, and raised ALT/AST may occur.

Sequelae of acute immunosuppression

  • CD4 count may transiently fall to <200 cells/mm3 (therefore, risk of opportunistic infections, particularly PCP).

  • Candidiasis, viral warts, VZV.

Management

  • The diagnosis of PHI will enable appropriate partner notification, screening for other STIs, and strategies to reduce onward transmission.

  • The decision of when to start HIV therapy is complex and should only be undertaken by clinicians experienced in this. There is growing evidence that early treatment improves outcomes and reduces population reservoirs, reducing transmission.

  • New infections may have resistance to one or more antiretroviral agents—knowledge of local resistance rates and the patient’s resistance profile is desirable before initiating antiretroviral therapy.

  • Early referral to an HIV specialist is essential. Patients should be seen by an HIV specialist within 24h if symptomatic/hospitalized with HIV or within 2 weeks otherwise.

Presentation with HIV complications and opportunistic infections

Degree of immunosuppression

  • The normal CD4 count is 500–1500 × 106 cells/mm3 and gradually decreases during the course of HIV infection.

  • The CD4 count is used as a guide to a patient’s susceptibility to complications of HIV infection (see Fig. 8.1). For example, Pneumocystis jiroveci (formerly known as P. carinii) pneumonia (PCP) is uncommon with a CD4 count >200.

Fig. 8.1 CD4 count is used as a guide to a patient’s susceptibility to complications of HIV infection.

Fig. 8.1 CD4 count is used as a guide to a patient’s susceptibility to complications of HIV infection.

Patients (who are aware of their HIV status) are usually familiar with these measures and are likely to be aware of their most recent results.

Risk group and predisposition to different complications

HIV in the UK is predominantly seen in specific patient groups, and the incidence of HIV-related complications varies between these groups.

  • MSM have a higher incidence of KS than other Caucasians.

  • Injecting drug users are more likely to be co-infected with hepatitis C and to develop sepsis related to injecting.

  • Individuals of African or Asian origin are more likely to present with TB (which may be atypical and/or extra-pulmonary in presentation).

  • Individuals of African origin are more likely to experience cryptococcal infection.

Travel history

Many infections in the HIV-infected patient represent reactivation of latent pathogens, and a travel history is helpful in the differential diagnosis, particularly for individuals presenting with pyrexia.

  • Histoplasmosis: travel to central America and eastern USA.

  • Coccidiomycosis: travel to South West USA and parts of South America.

  • Penicillinosis: travel to countries in South East Asia and Indonesia.

  • Strongyloides hyperinfection: previous travel in the tropics.

  • Leishmaniasis: travel in the Mediterranean, the Middle East, and the tropics.

Antiretroviral therapy

  • Patients who respond well to antiretroviral therapy (i.e. low HIV RNA load with a significant increase in CD4 count) have a markedly reduced risk from opportunistic complications of HIV infection. General medical/surgical conditions should be considered as being equally likely in successfully treated patients, as well as in those with untreated HIV infection with a high CD4 count.

  • However, antiretroviral therapy can cause toxicity and may present to the emergency clinician (Emergencies in HIV-positive patients Antiretroviral toxicity, pp. [link][link]).

  • Caution should be exercised when prescribing other drugs; use this from the University of Liverpool: Emergencies in HIV-positive patients https://www.hiv-druginteractions.org/

Clinical indicator diseases for adult HIV infection

(See Table 8.1.)

Fig. 8.2 The typical appearance of CMV retinitis in a patient with AIDS, characterized by retinal necrosis with an irregular granular border, patchy retinal haemorrhage, and retinal inflammatory sheathing of the retinal vessels.

Fig. 8.2 The typical appearance of CMV retinitis in a patient with AIDS, characterized by retinal necrosis with an irregular granular border, patchy retinal haemorrhage, and retinal inflammatory sheathing of the retinal vessels.

Reproduced from Easty D, et al. Oxford Textbook of Ophthalmology, 1999, with permission from Oxford University Press.

Acute neurological conditions in HIV-positive patients: assessment

Opportunistic infections and malignancies, the direct effect of HIV itself, and antiretroviral drugs can all cause disease of the CNS or peripheral nervous system. The presenting features of different conditions are often varied and non-specific and tend to involve the same diagnostic approach and investigations.

Key symptoms and signs

  • General: look for evidence of advanced immunosuppression (see Fig. 8.1).

  • Unconsciousness: assess and manage as described under Emergencies in HIV-positive patients Coma: assessment, pp. [link][link].

  • Seizure: requires urgent contrast CT, or preferably MRI, head scan to detect an SOL and, if none detected, suitability for diagnostic LP. Consider anti-epileptics, but be aware of antiretroviral and other drug interactions (sodium valproate commonly recommended if receiving protease inhibitor or non-nucleoside therapy). Lorazepam is preferable to diazepam for terminating seizures.

  • Headache: elucidate symptoms of raised ICP suggestive of an SOL such as nausea, early morning headache, and intensity on coughing. Distinguish from facial pain caused by dental, sinus, or herpetic neuralgia (check for herpetic rash).

  • Meningism: may be reduced or absent due to reduced inflammatory response. Aseptic meningitis can occur during PHI (seroconversion illness). With advancing immunosuppression, viral, bacterial, tuberculous, and fungal (cryptococcal) meningitides are more common and may not manifest typical signs of meningism.

  • Paraparesis: consider viral transverse myelitis (HIV, CMV, VZV, or HSV) or cord compression by infection or malignancy. Requires urgent MRI spine and subsequent LP if not contraindicated.

  • Cognitive impairment: wide differential. If associated with any focal neurological signs, consider SOL, PML, HIV dementia, and late syphilis.

  • Psychiatric disturbances: an organic cause is often found. May be a result of antiretroviral drugs themselves or their interactions with antipsychotic and recreational drugs. If aggressive, ensure the patient has no access to contaminated sharps.

  • Peripheral neuropathy: typically of gradual onset and caused by certain antiretrovirals or HIV itself.

  • Myopathy: zidovudine (AZT) and integrase inhibitors can cause myopathy or even rhabdomyolysis (check CK and renal function), arising from mitochondrial toxicity (Emergencies in HIV-positive patients Antiretroviral toxicity, pp. [link][link]). It may also be due to the concomitant use of lipid-lowering agents, and some antiretrovirals increase the levels of statins.

  • Rapid visual deterioration: consider CMV-related retinitis (often apparent on fundoscopy), Toxoplasma uveitis, endophthalmitis, intracerebral causes, and syphilis. Retinal detachment may be a consequence of treatment. Immediate referral to an ophthalmologist.

Acute neurological conditions in HIV-positive patients: investigations

Blood tests

  • Baseline (useful if already done—the patient will often know the results): CD4 cell count (but beware of CD4 counts taken during acute infections—these can be misleading), HIV RNA viral load, serology for Toxoplasma IgG (positive in >90% of patients with cerebral toxoplasmosis, indicative of risk of reactivation), CMV IgG, serological tests for syphilis (STS).

  • Routine: FBC (low lymphocyte count may give a clue to CD4 depletion), U&Es, LFTs.

  • Acute: inflammatory markers (CRP and ESR), syphilis testing, LDH (may be raised in lymphoma), blood cultures [bacterial, mycobacterial (4–6 weeks)]. Measure peripheral blood CMV DNA by PCR and serum cryptococcal antigen (CrAg) if CD4 count <200 cells/mm3 (positive in >80% with cryptococcal meningitis).

Specific

  • Stool, urine, and throat cultures: see Box 8.3 for LP.

  • CXR: consider TB at any CD4 count. Para-aortic and hilar lymphadenopathy might suggest Mycobacterium avian intracellulare (MAI) or lymphoma.

  • Contrast CT or MRI scan of the head:

    • Contrast essential, MRI more sensitive than CT (risk of missing brainstem disease, Toxoplasma cysts, and PML by CT).

    • Contrast-enhancing SOL very likely to be either cerebral toxoplasmosis (typically multiple, with ring enhancement, associated with oedema, at the basal ganglia or grey–white matter interface) or cerebral lymphoma (typically fewer lesions, with irregular enhancement, associated with oedema, periventricular). Poor response to empirical toxoplasmosis treatment suggests lymphoma. Less commonly, consider bacterial (e.g. Streptococcus, Nocardia), mycobacterial (e.g. tuberculoma), or fungal (e.g. cryptococcoma) lesions. Mycobacterial disease is on the increase, especially in ‘high-risk’ populations, e.g. patients from endemic TB areas.

    • Meningeal enhancement and hydrocephalus can occur in tuberculous, cryptococcal, or syphilitic meningitis.

    • PML: non-enhancing, multifocal, subcortical white matter changes. No mass effect.

    • HIV-associated dementia: non-enhancing, diffuse, deep white matter hyperintensities, with prominent cerebral atrophy. No mass effect.

    • Viral encephalitis (typically CMV, HSV, VZV) may display variably enhancing confluent changes, but often normal.

  • Brain biopsy: if disease stage and general prognosis fair, consider performing if no response to empirical treatment.

  • EEG: is useful to confirm seizure activity and response to treatment, but often non-specific for HIV encephalopathy and opportunistic infections.

  • Contrast MRI of the spine: the best modality for spinal cord and nerve root imaging.

  • NCS/EMG: useful if unusual or treatment-unresponsive sensory or motor symptoms and signs.

Acute neurological conditions in HIV-infected patients: treatment

(See Table 8.2.)

Table 8.2 Treatment for acute neurological conditions in HIV-infected patients

Condition

Possible presentations

Diagnostic tests

Treatment

HIV

Encephalitis or aseptic meningitis

Dementia/psychiatric presentation

Seizures

Diagnosis of exclusion

Brain biopsy diagnostic, but not performed for this reason

HAART

Toxoplasmosis

SOL

Seizures

Confusion

Encephalitic illness

90% anti-Toxoplasma antibody positive but does not discriminate active from inactive disease

CT: ring-enhancing lesions

Brain biopsy gold standard, perform if no response to empirical therapy

Sulfadiazine 1–2g IV/PO qds + pyrimethamine 100mg PO od on first day, then 75mg PO od + folinic acid 15mg PO od for 4–6 weeks

Clindamycin 1.2g PO/IV qds + pyrimethamine 100mg PO od on first day, then 75mg PO od + folinic acid 15mg PO od

Atovaquone 750mg PO tds for 21 days

(consider use of dexamethasone to reduce cerebral oedema)

Cryptococcosis

Headachec± meningism

SOL (cryptococcoma)

Seizures

Confusion

CSF: pleiocytosis with low glucose but may be normal in 20–30%. India ink stain, culture, and CrAg

Serum CrAg positive in 95%

Amphotericin 0.25mg–1mg/kg IV od for up to 6 weeks ± flucytosine 100mg/kg PO/IV qds for 2 weeks (liposomal formulations may be used if concerns regarding nephrotoxicity)

Fluconazole 400mg bd, daily/regular LPs to reduce ICP ≤20cmH2O is essential

Mycobacterium

Headache ± meningism

CSF: pleiocytosis with low glucose in most cases; ZN stain positive in only 10–20%. CSF culture takes 4–6 weeks

Obtain specialist microbiological advice; initiate therapy with at least four agents (preferably including those with CNS penetration, i.e. isoniazid + pyrazinamide), and consider steroids if fits or worsening neurological signs

Nocardia

Headache ± meningism, SOL (tuberculoma)

Seizures

Confusion

Brain biopsy/culture

Often coexisting pulmonary disease

Combination of at least 2 of co-trimoxazole, amikacin, streptomycin, imipenem (or meropenem) and minocycline

CMV

Encephalitis

Transverse myelitis

Polyradiculitis

Viral detection in CSF or neural tissue. PCR, culture, or immunohistochemistry

Ganciclovir 5mg/kg IV bd for 3 weeks

Valganciclovir 900mg PO bd for 3 weeks

Foscarnet 90mg/kg bd IV for 3 weeks

Varicella-zoster

Encephalitis

Transverse myelitis

Polyradiculitis

Viral detection in CSF or neural tissue. Culture, immunohistochemistry, or PCR

Aciclovir 10mg/kg IV tds for 10 days

Aciclovir 800mg five times daily for 5–10 days

Valaciclovir 1g PO tds for 1 week

Herpes simplex

Encephalitis

Radiculitis

Seizures

Viral detection in CSF or neural tissue. Culture, immunohistochemistry, or PCR

Aciclovir 10mg/kg IV tds for 14–21 days

PML (JC virus)

Motor dysfunction

Cranial nerve palsies

Dementia

CSF: anti-JC virus antibodies PCR

Brain biopsy

White matter MRI/CT changes

HAART

Lymphoma

SOL

Malignant meningitis

Isolated nerve or spinal cord lesion

CSF cytology

Brain biopsy

HAART + chemotherapy (treatment or palliative) + intracranial irradiation

Check BNF for contraindications, cautions, side effects, and interactions.

Respiratory emergencies in HIV-positive patients: assessment

Caution: HIV-infected patients presenting with cough warrant a high index of suspicion for M. tuberculosis which may be MDR. Such patients should wear a filter mask and be admitted to a side room. If on a ward with other immunocompromised patients, this should be with negative-pressure isolation facilities.

Key symptoms and signs

  • General: examination, including the oropharynx and lymphatic system, can give useful clues. Look for evidence of advanced immunosuppression and extra-pulmonary clues to the aetiology (e.g. cutaneous KS, neurological signs due to cryptococcosis, or retinitis due to CMV). Remember—multiple pathologies can coexist.

  • Cough productive of sputum: purulent sputum suggestive of bacterial or mycobacterial aetiology (incidence of Streptococcus pneumoniae, Haemophilus influenzae, and TB up to 100-fold higher than in HIV-negative controls). Also consider Staphylococcus aureus (in IVDUs) and Gram –ve organisms (e.g. Pseudomonas aeruginosa).

  • Non-productive cough: in patients with CD4 cell count <200 cells/mm3, the main concern is Pneumocystis jiroveci (previously carinii, a fungus) pneumonia (PCP), which typically has a chronic, progressive history associated with breathlessness (see Table 8.3). PCP can occasionally occur in patients during PHI (seroconversion illness) and can be seen in patients despite good adherence to co-trimoxazole prophylaxis. Other causes of non-productive cough include viral URTIs (any CD4 count), KS, lymphoma, and rarely lymphocytic interstitial pneumonitis (any CD4 count, but typically raised CD8 cell count with Sjögren’s symptoms).

  • Haemoptysis: is suggestive of mycobacterial or fungal causes, PE, or KS.

  • Breathlessness: if sudden onset, consider pneumothorax (secondary to PCP), pulmonary oedema, or PE. If gradual and progressive, need to exclude PCP.

  • Chest pain: is more common in bacterial infections, KS, pneumothorax, and PE. HIV-infected patients are more at risk of thromboembolic disease. Pneumothorax may complicate up to 10% of patients with PCP.

Table 8.3 Clinical, laboratory, and CXR findings that may distinguish PCP from bacterial pneumonia

Findings

PCP

Bacterial

CD4 cell count

<200 cells/mm3

Any

Symptoms

Non-productive cough

Productive cough

Purulent sputum

Symptom duration

A few weeks

3–5 days

Signs

Occasionally bilateral fine crackles (usually minimal signs)

Focal lung signs

Laboratory tests

WBC variable

WBC frequently elevated

Chest radiograph findings

Distribution

Diffuse > focal

Focal >diffuse

Location

Bilateral, perihilar initially

Unilateral, segmental/lobar

Pattern

Diffuse, interstitial infiltrates

Often lobar or focal consolidation

Cysts

10–15%

5–10% (Klebsiella, staphylococcal)

Pleural effusions

Very rare

25–30%

Respiratory emergencies in HIV-positive patients: investigations

Non-invasive investigations

NB Viral and fungal infections may cause few symptoms and signs—if suspected, request viral PCR and fungal microscopy and culture, in addition to the investigations listed here:

  • Baseline (useful if already done): CD4 cell count, HIV RNA viral load.

  • Radiology: CXR (see Table 8.4). Other radiology, such as US, CT, or HRCT, performed as needed.

  • FBC: leucopenia suggests poor prognosis in bacterial infections, and if pre-existing, can guide choice of empirical therapy.

  • U&Es: low Na+ or renal impairment suggests poor prognosis.

  • LFTs: abnormalities suggest disseminated disease or other pathology.

  • Serology: for Legionella (frequently tested by detection of urinary antigen), Mycoplasma, and other atypical pathogens.

  • Serum CrAg: a test with >90% sensitivity and >95% specificity for systemic cryptococcaemia.

  • ABGs: hypoxia can occur in any pneumonic process, but most characteristic of PCP.

  • Mantoux test (tuberculin skin testing): results can be misleading or unhelpful, as anergy is common. Only used in specific circumstances.

  • Exercise O2 saturation: significant exercise desaturation very suggestive of a diffuse pneumonitis such as PCP. Useful in patients with ‘normal’ CXR and SaO2 >93% at rest.

  • Lung function tests: if available, these may be useful as impaired gas transfer (KCO) has the same significance as O2 desaturation.

  • Blood cultures: often positive in S. pneumoniae infections. Mycobacterial blood cultures may be useful (4–6 weeks).

  • Sputum cultures: for microscopy and culture (including mycobacteria).

  • Induced sputum: nebulized hypertonic saline administered by specialist nurse or physiotherapist. Silver stain or immunofluorescence of induced sputum or BAL fluid has a sensitivity of 90% for PCP. Also send samples for microscopy and culture (bacterial and mycobacterial). Do not perform on an open ward.

Table 8.4 CXR patterns in HIV-associated disease

Radiological finding

Disease process

Normal

  • PCP, viral pneumonia (if hypoxic on exercise)

Focal infiltrate

  • Bacterial (S. pneumoniae, H. influenzae)

  • Mycobacteria (TB or MAI)

  • Fungal organisms (Cryptococcus, Histoplasma capsulatum, Aspergillus, Candida)

  • Patients may have atypical presentations, i.e. TB presenting with lower lobe consolidation/pleural effusion, instead of upper lobe cavity

  • Nocardia or Rhodococcus equi (rare)

  • Pulmonary KS or lymphoma

  • PCP (apical if on nebulized pentamidine prophylaxis)

Cavitating

  • Bacterial (staphylococcal, streptococcal, Nocardia, anaerobes)

  • Mycobacteria

  • Fungal organisms

  • PCP may produce thin-walled cysts (pneumatoceles)

Pneumothorax

  • PCP: occasionally when pneumatocele ruptures

  • TB

Diffuse infiltrate

  • PCP, classical presentation

  • Respiratory viruses (RSV, adenovirus, parainfluenza)

  • CMV (often difficult to decide whether pathogenic role)

  • Miliary TB

  • Fungal organisms

  • Toxoplasmosis

  • Lymphocytic interstitial pneumonitis

Pleural effusion

  • Bacterial (mainly S. pneumoniae)

  • Mycobacteria (mainly TB)

  • Lymphoma

  • Heart failure

  • KS

Mediastinal lymphadenopathy

  • Not a feature of HIV-related lymphadenopathy

  • Mycobacteria, fungal infection

  • Lymphoma and KS

Invasive investigations

  • Bronchoscopy: usually indicated if no response to treatment or second pathology suspected. Look carefully for KS lesions (transbronchial biopsies not routinely taken as risk of pneumothorax and haemorrhage). Send BAL samples for microscopy (including stains for pneumocystis) and culture (bacterial, fungal, and mycobacterial), viruses, and PCR.

  • Pleural aspiration: cell count, protein, microscopy and culture (bacterial and mycobacterial), cytology, LDH, and pH, and pleural biopsy of all significant effusions.

  • Lung biopsy: transbronchial, percutaneous, or open lung biopsy. Seek specialist advice.

Respiratory emergencies in HIV-positive patients: management

General measures

  • Monitor pulse, BP, and temperature regularly.

  • Pulse oximetry should be used with supplementary O2 to maintain saturations above 90%.

Assisted ventilation

Being HIV-infected is not, in itself, a contraindication to assisted ventilation or intensive care. Indeed, many acute respiratory infections requiring such support achieve excellent outcomes. It is the individual’s stage of disease and general prognosis that deem such management appropriate or inappropriate, as well as the views of the patient and their next of kin.

Specific treatment of respiratory conditions

(See Table 8.5.) Contact local microbiology or ID services if uncertain.

Table 8.5 Suggested treatment of respiratory conditions

Condition

Treatment

CAP (CD4 count >200 cells/mm3)

Co-amoxiclav IV/PO or ceftriaxone 2g od IV for 5–7 days

plus azithromycin 500mg od IV/PO for 3 days

CAP (CD4 count <200 cells/mm3)

Treat as per CAP for patients with CD4 count >200, but in addition, if there is any suggestion of PCP, treat as PCP as well

PCP

(if PaO2 <9.3kPa, add prednisolone 40mg bd PO for 5 days, then 40mg od for 5 days, then 20mg od for 10 days)

  • First line:

Co-trimoxazole 120mg/kg in four divided doses IV/PO for 21 days

(Before commencing co-trimoxazole, G6PD levels should be checked, but treatment should not be delayed while awaiting the result)

  • Second line:

Clindamycin 600mg–1.2g qds PO/IV + primaquine 15–30mg od PO for 14–21 days (not for G6PD-deficient patients) or

Pentamidine isetionate 4mg/kg od IV for 14–21 days

(3-day ‘crossover period’ is required if changing from first line to second line) or atovaquone 750mg PO bd for 21 days

Hospital-acquired pneumonia

Ceftazidime 2g tds IV or ciprofloxacin 500mg bd PO/IV for 5 days

Neutropenic patient (duration of treatment guided by microbiologist)

If any suggestion of PCP, treat as PCP plus

Piperacillin–tazobactam 4.5g tds IV for 7–14 days + azithromycin 500mg od IV/PO plus

Gentamicin (5mg/kg IV according to levels)

KS

HAART + chemotherapy

Lymphoma

HAART + chemotherapy

Treatment of aspergillosis, other fungi, nocardiosis, and CMV pneumonitis should be undertaken by clinicians experienced in the use of antimicrobials for these pathogens, given their increased toxicity and drug–drug interactions.

Gastrointestinal presentations in HIV-positive patients: assessment

Opportunistic infections, malignancies, and antiretroviral drug toxicity can all frequently manifest as symptoms/signs in the GIT.

Key symptoms and signs

  • General: assess hydration, weight, and nutritional status.

  • Diarrhoea: can be caused by multiple pathogens (both common and opportunistic) (see Table 8.5), drug therapy, or advanced HIV per se. The presence of associated symptoms (fever, abdominal pain, blood PR) should be established. An awareness of the CD4 count will assist in directing management.

  • Weight loss: can be caused by advanced HIV infection, may be the result of chronic diarrhoea/malabsorption, may be the presenting symptom of an underlying malignancy or opportunistic infection, or may represent toxicity to antiretroviral therapy (particularly subcutaneous fat loss).

  • Abdominal pain: can be a feature of GI infections (see Table 8.5), biliary tree disease, or pancreatitis—which may be drug-induced, notably by nucleoside analogues, particularly didanosine. Lactic acidosis and hepatic steatosis are rare complications of antiretroviral therapy that may present as vague abdominal pain.

  • Loin pain/nephrolithiasis: is a well-recognized side effect of indinavir therapy. Stones are unlikely to be seen on plain X-rays and usually respond to conservative management with fluid input, without the need to discontinue the offending agent. With severe episodes (haematuria and confirmed calculi on renal tract investigation), change therapy as there is a risk of further episodes and progressive renal damage.

  • Jaundice: may be the result of viral hepatitis (acute or chronic), biliary tract disease, drug-induced hepatitis, or hepatic involvement by other opportunistic infections or tumours. Also associated with atazanavir where, for this specific drug, the development of unconjugated hyperbilirubinaemia may occur in susceptible individuals who have minor abnormalities of the bile acid transporter genes (e.g. MDR). It is a benign side effect but can cause significant jaundice in some patients.

  • Dysphagia: is most commonly caused by candidal infection (oral Candida is usually present), and less commonly by ulceration secondary to HSV, VZV, CMV, or idiopathic (aphthous).

  • Oral lesions: oral Candida (usually in a pseudomembranous form, appearing as white plaques, but may be erythematous or hyperplastic) and oral hairy leukoplakia (white plaques on the side of the tongue) are common signs in individuals with HIV infection and may be the first presenting features of advancing infection. KS may present as red/purple macules on the palate or gingival margin. Oral chancres of primary syphilis may occasionally be seen, in MSM more frequently than in heterosexual patients.

Gastrointestinal presentations in HIV-positive patients: investigations

General investigations

  • FBC, U&Es, LFTs, CRP: check for evidence of anaemia, dehydration, and hepatic dysfunction.

  • Blood cultures: bacterial GI infections are more likely to be accompanied by systemic infection in the immunocompromised host. Mycobacterial blood cultures (particularly considering atypical mycobacteria in individuals with CD4 counts <100 cells/mm3).

  • Amylase: check for pancreatitis in individuals with abdominal pain.

  • Uncuffed serum lactate: consider the possibility of lactic acidosis in the unwell patient receiving antiretroviral therapy with non-specific abdominal symptoms. Send to a lab rapidly for an accurate result.

  • Hepatitis serology: consider acute hepatitis A/B/E (or hepatitis D super-infection if already HBV-positive) in the jaundiced patient and chronic hepatitis B/C in patients with evidence of chronic liver disease. New onset of abnormal LFTs may be due to hepatitis C.

  • Syphilis serology.

  • Rectal/genital STI swabs: send swabs for Chlamydia/LGV/gonorrhoea if there are rectal/lower GI symptoms.

Specific investigations

  • Stool specimens: should be examined/cultured for bacteria and ova, cysts, and parasites. At least three stool specimens should be sent. Clostridium difficile toxin should be requested in individuals who have taken or are taking antibiotics. In an individual with severe immunosuppression (CD4 count <100 cells/mm3) and negative conventional stool analysis, examination for microsporidial species should be performed.

  • AXR: look for evidence of toxic dilatation in the patient presenting with diarrhoea/abdominal pain. The major causes are CMV (with CD4 count <100 cells/mm3) and bacterial infections (Salmonella, Shigella, Campylobacter) at higher CD4 counts.

  • USS: look for evidence of hepatic/biliary abnormality in patients with jaundice/abnormal LFTs, evidence of ascites in patients with abdominal distension, and abdominal masses/lymphadenopathy in individuals with opportunistic infections/tumours.

  • CT scanning: look for evidence of masses/lymphadenopathy in individuals with abdominal pain, which may represent involvement by underlying opportunistic infections or tumours.

  • Upper GI endoscopy: look for oesophageal lesions in patients with dysphagia and gastric lesions in patients with abdominal pain. Perform duodenal biopsies in individuals with chronic diarrhoea where no pathogen has been isolated.

  • Sigmoidoscopy/colonoscopy: look for evidence of involvement by opportunistic pathogens/tumours in patients with chronic diarrhoea or abdominal pain. Rectal/colonic biopsies should be performed in patients with chronic diarrhoea where no pathogen has been isolated.

  • ERCP/MRCP: should be considered in individuals with evidence of obstructive jaundice where no cause has been found, or in individuals with chronic abdominal pain looking for any evidence of ascending cholangitis.

Gastrointestinal presentations in HIV-positive patients: management

  • General principles of rehydration, analgesia, and nutritional support should apply.

  • If the CD4 count is >200 cells/mm3, patients are usually treated in a similar way to HIV-seronegative individuals.

  • Specific therapy should be directed towards the suspected/proven underlying cause (see Table 8.6). Consider empiric treatment with antibacterial agents for acute diarrhoea where a bacterial cause is likely. This should be treated according to sensitivities and local protocol, unless the patient is compromised. In the unwell patient with diarrhoea, consider additional anti-CMV therapy (usually ganciclovir) if the CD4 count is <100 cells/mm3.

  • Antiretroviral therapy should not be discontinued or modified without discussion with an experienced HIV clinician.

Table 8.6 GI pathogens in HIV-positive patients

Pathogen

Clinical presentation

Diagnosis

Treatment

Candida

Oral: usually white plaques. Usually CD4 count <350

Oesophageal: dysphagia or odynophagia. Usually CD4 count <200

Usually based upon clinical appearance

Can be confirmed by biopsy/culture

Oral: usually with fluconazole (50mg × 5 days) or 400mg stat

Oesophageal: fluconazole 100mg od × 14 days

Alternative agents may be recommended in cases of suspected/proven ‘azole’ resistance

Salmonella

Diarrhoea ± fever, abdominal pain, and blood PR; colonic dilatation ± any CD4 count

Confirmed by stool (± blood) cultures

Empiric treatment may be considered in the unwell patient

Ciprofloxacin 500mg bd × 7–14 days

Cephalosporin if ciprofloxacin-intolerant or resistant

Shigella

Diarrhoea ± fever, abdominal pain, and blood PR; colonic dilatation ± any CD4 count

Confirmed by stool (± blood) cultures

Empiric treatment may be considered in the unwell patient

Ciprofloxacin 500mg bd × 7–14 days

Trimethoprim if ciprofloxacin-intolerant or resistant

Campylobacter

Diarrhoea ± fever, abdominal pain, and blood PR; colonic dilatation ± any CD4 count

Confirmed by stool (± blood) cultures

Empiric treatment may be considered in the unwell patient

Ciprofloxacin 500mg bd × 7–14 days

Azithromycin if ciprofloxacin-intolerant or resistant

Crytosporidia

May present acutely as ‘traveller’s diarrhoea’ at any CD4 count which usually clears spontaneously, or chronically as watery diarrhoea with CD4 count <100

Demonstration of organism on stool analysis and/or biopsy

No proven effective antimicrobial therapy (consider nitazoxanide). Acute cryptosporidial infection usually resolves spontaneously; treat chronic infection with HAART

Microsporidia

Watery diarrhoea in individuals with CD4 count <100

Demonstration of organisms by specific stool analysis or on biopsy/electron microscopy

Albendazole is beneficial in some studies. Effective HIV treatment results in clinical improvement

Isospora

Watery diarrhoea in individuals with CD4 count <100

AFB smear of stool

Co-trimoxazole usually effective

Entamoeba histolytica

Diarrhoea ± blood and abdominal pain. Any CD4 count

Ova, cysts, and parasites of stool

Metronidazole 800mg tds or tinidazole, then diloxanide

Giardia

Watery diarrhoea. Any CD4 count

Ova, cysts, and parasites of stool

Metronidazole 400mg tds for 10 days or tinidazole 2g PO on days 1 and 5

CMV

Oesophageal: dysphagia with ulceration

Gastric/upper GI: abdominal pain

Colonic: diarrhoea ± abdominal pain. Toxic dilatation may occur.

CD4 <100

Demonstration of organisms by immunocytochemistry of biopsy specimens

Specific CMV therapy (usually ganciclovir 5mg/kg bd for 3–4 weeks).

Effective anti-HIV therapy should reduce risk of recurrence/other end-organ disease

Herpes simplex

Oesophageal ulceration, or proctitis/colitis

Demonstration of organisms on biopsy/culture

Aciclovir 200–800mg 5×/day or 5mg/kg IV for 2–3 weeks

Herpes zoster

Oesopha-geal ul-ceration

Demonstra-tion of or-ganisms on bi-op-sy/cultu-re

Aciclovir 400–800mg 5×/day or 5–10mg/kg IV for 2–3 weeks

Mycobacterium avium complex

Chronic, watery diarrhoea ± ab-dominal pain. Usually systemic symptoms (fever, weight loss, pancyto-penia). CD4 count <50

Blood cultures (specific mycobac-terial culture: may take several weeks) or demon-stration of organisms on biopsy

Three agents (usually rifabutin, ethambutol, and clarithromycin or azithromycin)Effective anti-HIV therapy is associated with clinical response

Clostridium difficile

Watery diarrhoea. History of antibiotics Any CD4 count

Stool toxin assay

Stop culprit antibiotic(s) if possibleMetronidazole 400mg tds PO–10 daysVancomycin 125mg qds × 10 days

Pyrexia of unknown origin

Assessment

  • Look for signs/symptoms of focal infection.

  • Check for neutropenia.

  • Consider TB.

  • Consider line sepsis if indwelling IV cannulae.

  • Consider drug-related fever (detailed drug history, including antiretroviral agents).

  • Consider underlying lymphoma.

  • Detailed travel history is essential.

Investigations

  • Usual investigation of fever.

  • CrAg.

  • Mycobacterial blood cultures (MAI if CD4 count <100 cells/mm3).

  • Consider:

    • CT scan head.

    • CT scan chest and abdomen.

    • Lymph node biopsy (if significant lymphadenopathy).

    • Bone marrow examination.

    • Fludeoxyglucose positron emission tomography (FDG-PET) CT body.

Treatment

  • Unless clinically unwell, most clinicians would recommend withholding empiric antimicrobial therapy.

  • Specific antimicrobial (or other) therapy should be directed against the suspected underlying pathogen/process.

Immune reconstitution inflammatory syndrome

  • Immune reconstitution inflammatory syndrome (IRIS) may be seen, following the commencement of antiretroviral therapy in patients with HIV. It is characterized by an inflammatory response associated with worsening of pre-existing infections. These infections may have been previously diagnosed and treated or may be unmasked by the patient’s regained ability to mount an inflammatory response.

  • This inflammatory reaction is usually self-limited, particularly when the pre-existing infection is effectively treated. However, long-term complications and adverse outcomes may rarely be seen, particularly in patients with neurological involvement.

  • The clinical features of IRIS are highly variable, but the most common presentations are with fever and lymphadenopathy. The main risk factors for IRIS are a low baseline CD4 count and/or a rapid recovery of CD4 and a rapid fall in viral load after initiation of HAART. Most patients with IRIS develop symptoms within 7 days to a few months after initiation of antiretroviral treatment.

  • In order to reduce the likelihood of IRIS, antiretroviral therapy may be delayed for 1–2 months while treating a known opportunistic infection with the appropriate antimicrobial. Antiretroviral therapy should only be delayed for about 2 weeks in patients infected with M. tuberculosis who have a CD4 cell count <100 cells/mm3.

  • IRIS is generally a diagnosis of exclusion. The possibility of drug reaction or resistance, patient non-compliance, and persistently active infection should be excluded first. For example, abacavir hypersensitivity may be confused with IRIS, but symptoms are exacerbated following each dose of abacavir.

  • When IRIS is thought to be highly likely, further invasive diagnostic procedures to find an occult infection may be delayed. Start or continue to treat the underlying pathogen in patients with IRIS. Continue antiretroviral therapy in most patients, except for cases when the presentation of IRIS is life- or organ-threatening. Steroids may reduce the inflammatory response in some cases. When it is decided to use steroids, prednisolone or methylprednisolone may be given initially at a daily dose of 1–1.5mg/kg (60–80mg) and then tapered, while monitoring for recurrence of clinical symptoms, over weeks to months.

Dermatological presentations

  • Seroconversion can present with a viral exanthematous rash.

  • Consider drug-related causes (including antiretroviral agents), but do not discontinue antiretroviral agents (unless essential) without discussion with an HIV clinician.

  • In particular, patients recently having commenced nevirapine therapy may be at risk of Stevens–Johnson syndrome or toxic epidermal necrolysis, and patients having recently commenced abacavir may be at risk of a hypersensitivity syndrome (Emergencies in HIV-positive patients Antiretroviral toxicity, pp. [link][link]). Milder rashes are common after initiation of any antiretroviral and usually self-limiting, and usually HAART can be continued with an antihistamine for symptom control.

  • Most dermatological complaints can behave atypically and more severely in individuals with HIV infection:

    • Shingles (varicella-zoster) may present with multi-dermatomal lesions and/or neurological involvement.

    • Herpes simplex may present with more severe lesions, more frequent recurrences, or prolonged outbreaks. There may also be neurological involvement, requiring higher doses of aciclovir than used in immunocompetent patients.

    • Seborrhoeic dermatitis may present more aggressively in the HIV-positive patient and may be recalcitrant to conventional therapy.

    • Early syphilis should be considered in any HIV-positive patient with dermatological lesions.

Haematological presentations

Cytopenias may be the result of HIV infection per se, antiretroviral (or other drug) toxicity, or bone marrow involvement by opportunistic infections or tumours.

  • Mild to moderate thrombocytopenia is a common finding in the HIV-infected patient; a severe idiopathic thrombocytopenic purpura (ITP) picture is well recognized. Usually responds to antiretroviral therapy, but steroids/Ig may be required in severe cases.

  • Anaemia is a recognized side effect of antiretroviral therapy—notably zidovudine (AZT) therapy.

  • Neutropenia is a recognized side effect of zidovudine (AZT) and ganciclovir therapy, and occurs more frequently in the HIV-infected patient receiving chemotherapy for malignancy. Standard management of neutropenia should apply.

Antiretroviral toxicity

  • Newer agents tend to be less toxic than older agents (such as zidovudine, didanosine, and stavudine), which are now less commonly used.

  • Many clinicians are unfamiliar with the agents used to treat HIV infection. They are associated with multiple toxicities, some of which may present to the emergency clinician. Always consider discussing the case with a clinician experienced in the use and toxicity of these drugs.

  • The key principles of management are to recognize the possibility of iatrogenic illness and to exert caution in management. In order to minimize the risk of development of resistance and to preserve future treatment options, antiretroviral agents should be discontinued only in discussion with an HIV clinician. If necessary, the toxic agent is switched and the withdrawal of one or two of a combination of agents (thus leaving an individual on suboptimal therapy) should be avoided.

  • In individuals receiving antiretroviral therapy who present systemically unwell, the possibility of lactic acidosis should always be considered (see Emergencies in HIV-positive patients Mitochondrial toxicity, pp. [link][link]).

Rash and hypersensitivity

  • Abacavir hypersensitivity reaction (4%) can present as a fever or maculopapular rash (usually in the first 2 months of treatment), often associated with one or more other symptoms or signs (fever, sore throat, GI or respiratory symptoms, laboratory abnormalities). If strongly suspected, abacavir should be discontinued and the patient never rechallenged (risk of fatal hypersensitivity reaction). This decision should be taken by an experienced HIV clinician. Most clinicians now use the HLA-B5701 test to predict the likelihood of abacavir hypersensitivity (90% risk).

  • Non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine): maculopapular rash (~10%), peaking at 2 weeks, often associated with abnormal LFTs. Sometimes can be ‘pushed through’ with antihistamines (cetirizine) but needs close monitoring (associated severe or life-threatening hepatotoxicity not uncommon). Stevens–Johnson syndrome and toxic epidermal necrolysis are well recognized, but uncommon, side effects of nevirapine. Stevens–Johnson syndrome is more common in patients who start treatment with high CD4 counts. Nevirapine should not be used in patients with a high CD4 count, as it increases the risk of Stevens–Johnson syndrome.

Mitochondrial toxicity

Usually attributed to the unwanted inhibition of mitochondrial DNA polymerase gamma by nucleoside reverse transcriptase inhibitors (particularly stavudine and didanosine). Over months, this can lead to mitochondrial dysfunction which can manifest as:

  • Lactic acidosis/hepatic steatosis resulting from general mitochondrial dysfunction. If suspected (general malaise, abdominal pain, metabolic acidosis, abnormal LFTs), an uncuffed blood sample should be sent for immediate lactate measurement, and if high (>5mmol/L) with associated acidosis, the offending drug(s) stopped. This condition can be rapidly fatal, and admission to ICU is occasionally required.

  • Acute pancreatitis: particularly associated with didanosine (ddI) (also precipitated by alcohol, gallstones, pentamidine, and some opportunistic infections).

  • Myopathy (muscle biopsy diagnostic): zidovudine (AZT).

  • Antiretroviral-induced peripheral neuropathy: particularly associated with zalcitabine, stavudine, and didanosine.

  • Renal tubular acidosis/Fanconi’s syndrome has been rarely reported with tenofovir.

Metabolic disturbances

Hyperlipidaemia and glucose intolerance (including frank diabetes) have been associated with the use of antiretroviral therapy, particularly protease inhibitors. The association with premature cardiovascular disease currently remains uncertain but is suggested by some cohort studies. The prescription of statins in this patient group should be made with care, given the potential drug–drug interactions; simvastatin is contraindicated in patients receiving protease inhibitors (pravastatin or atorvastatin are preferred).

Haematological toxicity

Nucleoside analogues—particularly zidovudine (AZT)—are associated with haematological toxicity, especially anaemia and neutropenia, which usually occurs during the first few weeks/months of therapy.

Hepatotoxicity

All of the available antiretroviral agents have been associated with hepatotoxicity, particularly in those individuals co-infected with hepatitis C/B. Nevirapine has been rarely associated with fulminant hepatitis (within the first 6 weeks of therapy). Hepatic steatosis (as part of a syndrome of mitochondrial dysfunction—as outlined earlier) is a well-recognized, though rare, complication of nucleoside analogue therapy. Most HIV physicians would closely monitor LFTs without discontinuation, unless there is evidence of clinical hepatitis or an ALT/AST of >5–10 times the upper limit of normal.

Neurological toxicity

Efavirenz (and occasionally nevirapine) can cause significant neuropsychiatric disease. In the majority of patients, this occurs in the first 4 weeks of therapy and can present as mood swings or depression. Treatment is discontinued in 5–10% of individuals, though up to 50% will experience some symptoms of ‘muzzy head’ or nightmares.

Drug interactions with antiretroviral therapy

Protease inhibitors and non-nucleoside reverse transcriptase inhibitors are metabolized through the cytochrome P450 system and exhibit a wide variety of drug interactions, many of which have potentially serious consequences. It is recommended that co-administration of other P450-mediated agents should be with caution.

Further information is available in the BNF or can be accessed via the University of Liverpool website at Emergencies in HIV-positive patients https://www.hiv-druginteractions.org

Post-exposure prophylaxis

Evidence that PEP may be effective can be drawn from both animal and vertical transmission studies. The most compelling data are from a case-controlled study of health-care workers where the administration of zidovudine (AZT) monotherapy was shown to be associated with ~80% reduction in HIV transmission.

Most hospitals/emergency departments will have established protocols for the management of PEP (see Box 8.4). However, the following general principles apply:

  • The risk of HIV transmission is the product of the risk of the ‘donor’ being HIV-positive and the risk of HIV infection from the exposure.

  • To estimate the risk of the donor being HIV-positive, an understanding of the epidemiology of the ‘risk group’ of the individual is helpful.

    • For example, the risk of a sexually active homosexual man in the UK being HIV-positive is estimated at ~12.5% in London and 5.9% across the UK as a whole.

    • The risk of an IVDU being HIV-positive is <1.1%.

    • The risk of a heterosexual being HIV-positive requires knowledge of the HIV prevalence in the country in which they have been sexually active (as high as 20–50% in some sub-Saharan African countries). In the black African population in the UK, prevalence has been estimated at 4.1% among men and 7.1% among women.

Inoculation injuries

The risk of HIV transmission from exposures has been estimated at:

  • Needle-stick injury: 1 in 333.

  • Splash injury (to eyes or diseased skin): <1 in 1000.

  • Human bite: <1 in 10 000 (PEP not recommended).

  • Injury from discarded sharps in the community: risk usually low, as HIV becomes non-viable after a few hours and the use of the sharps prior to being discarded is usually unknown.

NB Do not forget that optimal management of sharps injuries includes immediate wound management (bleeding and simple washing) and consideration of exposure to hepatitis B (assess vaccination status and consider accelerated vaccination or Ig) and hepatitis C.

Sexual exposure

The risk of HIV transmission through sexual exposure from a known HIV-positive individual not on HAART is estimated at:

  • Unprotected receptive vaginal sex (♂ to ♀): 1 in 1000.

  • Unprotected insertive vaginal sex (♀ to ♂): 1 in 1219.

  • Unprotected anal sex (risk to insertive partner): 1 in 666.

  • Unprotected anal sex (risk to receptive partner): 1 in 90.

  • Oral sex with ejaculation (both receptive and insertive): <1 in 10 000.

Factors associated with increased risk include

  • Donor: advanced HIV infection; high viral load.

  • Injury: hollow-bore needle; insertion of needle into artery or vein of the patient; visible blood on device; deep injury.

Following assessment of the risk, consider PEP.

Given the potential opportunities for future risk reduction and concerns regarding PEP efficacy, HIV resistance, and drug toxicity in this setting, it is recommended that the decision to administer PEP after sexual exposure is taken in conjunction with clinicians experienced in GUM/HIV medicine.

More guidance can be found at Emergencies in HIV-positive patients https://www.bashhguidelines.org/media/1027/pepse-2015.pdf