Epidemiology
- Incidence: 10.00 cases per 100,000 person-years
- Peak incidence: 30-40 years
- Sex ratio: more common in males 3:1
| <1 | 1-5 | 6+ | 16+ | 30+ | 40+ | 50+ | 60+ | 70+ | 80+ |
Pathophysiology
Basics
Basics structure
Cell entry
Replication
- HIV is a RNA retrovirus of the lentivirus genus (lentiviruses are characterized by a long incubation period)
- two variants - HIV-1 and HIV-2
- HIV-2 is more common in west Africa, has a lower transmission rate and is thought to be less pathogenic with a slower progression to AIDS
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Basics structure
- spherical in shape with two copies of single-stranded RNA enclosed by a capsid of the viral protein p24
- a matrix composed of viral protein p17 surrounds the capsid
- envelope proteins: gp120 and gp41
- pol gene encodes for viral enzymes reverse transcriptase, integrase and HIV protease
Cell entry
- HIV can infect CD4 T cells, macrophages and dendritic cells
- gp120 binds to CD4 and CXCR4 on T cells and CD4 and CCR5 on macrophages
- mutations in CCR5 can give immunity to HIV
Replication
- after entering a cell the enzyme reverse transcriptase creates dsDNA from the RNA for integration into the host cell's genome
Clinical features
HIV seroconversion
HIV seroconversion is symptomatic in 60-80% of patients and typically presents as a glandular fever type illness. Increased symptomatic severity is associated with poorer long term prognosis. It typically occurs 3-12 weeks after infection
Features
Diagnosis
HIV seroconversion is symptomatic in 60-80% of patients and typically presents as a glandular fever type illness. Increased symptomatic severity is associated with poorer long term prognosis. It typically occurs 3-12 weeks after infection
Features
- sore throat
- lymphadenopathy
- malaise, myalgia, arthralgia
- diarrhoea
- maculopapular rash
- mouth ulcers
- rarely meningoencephalitis
Diagnosis
- antibodies to HIV may not be present
- HIV PCR and p24 antigen tests can confirm diagnosis
Investigations
HIV antibody test
p24 antigen test
- most common and accurate test
- usually consists of both a screening ELISA (Enzyme Linked Immuno-Sorbent Assay) test and a confirmatory Western Blot Assay
- most people develop antibodies to HIV at 4-6 weeks but 99% do by 3 months
p24 antigen test
- usually positive from about 1 week to 3 - 4 weeks after infection with HIV
- sometimes used as an additional screening test in blood banks
Management
Highly active anti-retroviral therapy (HAART) involves a combination of at least three drugs, typically two nucleoside reverse transcriptase inhibitors (NRTI) and either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). This combination both decreases viral replication but also reduces the risk of viral resistance emerging
Following the 2015 BHIVA guidelines it is now recommended that patients start HAART as soon as they have been diagnosed with HIV, rather than waiting until a particular CD4 count, as was previously advocated.
Entry inhibitors
Nucleoside analogue reverse transcriptase inhibitors (NRTI)
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Protease inhibitors (PI)
Integrase inhibitors
Following the 2015 BHIVA guidelines it is now recommended that patients start HAART as soon as they have been diagnosed with HIV, rather than waiting until a particular CD4 count, as was previously advocated.
Entry inhibitors
- maraviroc (binds to CCR5, preventing an interaction with gp41), enfuvirtide (binds to gp41, also known as a 'fusion inhibitor')
- prevent HIV-1 from entering and infecting immune cells
Nucleoside analogue reverse transcriptase inhibitors (NRTI)
- examples: zidovudine (AZT), abacavir, emtricitabine, didanosine, lamivudine, stavudine, zalcitabine, tenofovir
- general NRTI side-effects: peripheral neuropathy
- tenofovir: used in BHIVAs two recommended regime NRTI. Adverse effects include renal impairment and ostesoporosis
- zidovudine: anaemia, myopathy, black nails
- didanosine: pancreatitis
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
- examples: nevirapine, efavirenz
- side-effects: P450 enzyme interaction (nevirapine induces), rashes
Protease inhibitors (PI)
- examples: indinavir, nelfinavir, ritonavir, saquinavir
- side-effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition
- indinavir: renal stones, asymptomatic hyperbilirubinaemia
- ritonavir: a potent inhibitor of the P450 system
Integrase inhibitors
- examples: raltegravir, elvitegravir, dolutegravir
Complications
The table below shows the infections and other disorders that may be encountered by patients with HIV according to the CD4 count.
Pneumocystis jiroveci pneumonia
Whilst the organism Pneumocystis carinii is now referred to as Pneumocystis jiroveci, the term Pneumocystis carinii pneumonia (PCP) is still in common use
Features
Pneumothorax is a common complication of PCP.
Extrapulmonary manifestations are rare (1-2% of cases), may cause
Kaposi's sarcoma
Cytomegalovirus (CMV) retinitis is common, affecting 30-40% of patients who have a CD4 count < 50. Diagnosis is clinical as there are no diagnostic tests
Features
Fundoscopy
Management
Focal neurological lesions
Toxoplasmosis
Primary CNS lymphoma
Differentiating between toxoplasmosis and lymphoma is a common clinical scenario in HIV patients. It is clearly important given the vastly different treatment strategies. The table below gives some general differences. Please see the Radiopaedia link for more details.
Tuberculosis
Encephalitis
Cryptococcus
Progressive multifocal leukoencephalopathy (PML)
AIDS dementia complex
CD4 count 200 - 500 cells/mm³
| Disorder | Notes |
|---|---|
| Oral thrush | Secondary to Candida albicans |
| Shingles | Secondary to herpes zoster |
| Hairy leukoplakia | Secondary to EBV |
| Kaposi sarcoma | Secondary to HHV-8 |
CD4 count 100 - 200 cells/mm³
| Disorder | Notes |
|---|---|
| Cryptosporidiosis | Whilst patients with a CD4 count of 200-500 may develop cryptosporidiosis the disease is usually self-limiting and similar to that in immunocompetent hosts |
| Cerebral toxoplasmosis | |
| Progressive multifocal leukoencephalopathy | Secondary to the JC virus |
| Pneumocystis jirovecii pneumonia | |
| HIV dementia |
CD4 count 50 - 100 cells/mm³
| Disorder | Notes |
|---|---|
| Aspergillosis | Secondary to Aspergillus fumigatus |
| Oesophageal candidiasis | Secondary to Candida albicans |
| Cryptococcal meningitis | |
| Primary CNS lymphoma | Secondary to EBV |
CD4 count < 50 cells/mm³
| Disorder | Notes |
|---|---|
| Cytomegalovirus retinitis | Affects around 30-40% of patients with CD4 < 50 cells/mm³ |
| Mycobacterium avium-intracellulare infection |
Pneumocystis jiroveci pneumonia
Whilst the organism Pneumocystis carinii is now referred to as Pneumocystis jiroveci, the term Pneumocystis carinii pneumonia (PCP) is still in common use
- Pneumocystis jiroveci is an unicellular eukaryote, generally classified as a fungus but some authorities consider it a protozoa
- PCP is the most common opportunistic infection in AIDS
- all patients with a CD4 count < 200/mm³ should receive PCP prophylaxis
Features
- dyspnoea
- dry cough
- fever
- very few chest signs
Pneumothorax is a common complication of PCP.
Extrapulmonary manifestations are rare (1-2% of cases), may cause
- hepatosplenomegaly
- lymphadenopathy
- choroid lesions
Dermatological
Kaposi's sarcoma
- caused by HHV-8 (human herpes virus 8)
- presents as purple papules or plaques on the skin or mucosa (e.g. gastrointestinal and respiratory tract)
- skin lesions may later ulcerate
- respiratory involvement may cause massive haemoptysis and pleural effusion
- radiotherapy + resection
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Kaposi's sarcoma in a patient with HIV
Ocular
Cytomegalovirus (CMV) retinitis is common, affecting 30-40% of patients who have a CD4 count < 50. Diagnosis is clinical as there are no diagnostic tests
Features
- visual impairment - 'blurred vision' etc
Fundoscopy
- characteristic appearance showing retinal haemorrhages and necrosis
- often called 'pizza' retina
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Fundus photograph showing CMV retinitis. Credit: National Eye Institute, National Institutes of Health
Management
- IV ganciclovir
- treatment used to be life-long but new evidence suggests that it may be discontinued once CD4 > 150 after HAART
- alternative: IV foscarnet or cidofovir
Neurological
Focal neurological lesions
Toxoplasmosis
- accounts for around 50% of cerebral lesions in patients with HIV
- constitutional symptoms, headache, confusion, drowsiness
- CT: usually single or multiple ring enhancing lesions, mass effect may be seen
- management: sulfadiazine and pyrimethamine
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| © Image used on license from Radiopaedia | |
Cerebral toxoplasmosis: CT scan with contrast showing multiple ring enhancing lesions
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| © Image used on license from Radiopaedia | |
Cerebral toxoplasmosis: MRI (T1 C+) demonstrates multiple small peripherally enhancing nodules located predominantly in the basal ganglia as well as the central portions of the cerebellar hemispheres. Only a small amount of surrounding oedema is present.
Primary CNS lymphoma
- accounts for around 30% of cerebral lesions
- associated with the Epstein-Barr virus
- CT: single or multiple homogenous enhancing lesions
- treatment generally involves steroids (may significantly reduce tumour size), chemotherapy (e.g. methotrexate) + with or without whole brain irradiation. Surgical may be considered for lower grade tumours
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| © Image used on license from Radiopaedia | |
Primary CNS lymphoma: Non-contrast CT demonstrates a hyper-attenuating mass adjacent to the left lateral ventricle, with no calcification or haemorrhage.
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| © Image used on license from Radiopaedia | |
Primary CNS lymphoma: MRI (T1 C+) demonstrates a large multilobulated mass in the right frontal lobe. It homogeneously enhances and extends to involve the caudate and the periventricular area. There is significant mass effect.
Differentiating between toxoplasmosis and lymphoma is a common clinical scenario in HIV patients. It is clearly important given the vastly different treatment strategies. The table below gives some general differences. Please see the Radiopaedia link for more details.
| Toxoplasmosis | Lymphoma |
|---|---|
| Multiple lesions Ring or nodular enhancement Thallium SPECT negative | Single lesion Solid (homogenous) enhancement Thallium SPECT positive |
Tuberculosis
- much less common than toxoplasmosis or primary CNS lymphoma
- CT: single enhancing lesion
Generalised neurological disease
Encephalitis
- may be due to CMV or HIV itself
- HSV encephalitis but is relatively rare in the context of HIV
- CT: oedematous brain
Cryptococcus
- most common fungal infection of CNS
- headache, fever, malaise, nausea/vomiting, seizures, focal neurological deficit
- CSF: high opening pressure, India ink test positive
- CT: meningeal enhancement, cerebral oedema
- meningitis is typical presentation but may occasionally cause a space occupying lesion
Progressive multifocal leukoencephalopathy (PML)
- widespread demyelination
- due to infection of oligodendrocytes by JC virus (a polyoma DNA virus)
- symptoms, subacute onset : behavioural changes, speech, motor, visual impairment
- CT: single or multiple lesions, no mass effect, don't usually enhance. MRI is better - high-signal demyelinating white matter lesions are seen
AIDS dementia complex
- caused by HIV virus itself
- symptoms: behavioural changes, motor impairment
- CT: cortical and subcortical atrophy