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
  • 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


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
  • antibodies to HIV may not be present
  • HIV PCR and p24 antigen tests can confirm diagnosis

Investigations

HIV antibody 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
  • 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.

CD4 count 200 - 500 cells/mm³

DisorderNotes
Oral thrushSecondary to Candida albicans
ShinglesSecondary to herpes zoster
Hairy leukoplakiaSecondary to EBV
Kaposi sarcomaSecondary to HHV-8

CD4 count 100 - 200 cells/mm³

DisorderNotes
CryptosporidiosisWhilst 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 leukoencephalopathySecondary to the JC virus
Pneumocystis jirovecii pneumonia
HIV dementia

CD4 count 50 - 100 cells/mm³

DisorderNotes
AspergillosisSecondary to Aspergillus fumigatus
Oesophageal candidiasisSecondary to Candida albicans
Cryptococcal meningitis
Primary CNS lymphomaSecondary to EBV

CD4 count < 50 cells/mm³

DisorderNotes
Cytomegalovirus retinitisAffects 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


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

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

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

© Image used on license from Radiopaedia
Cerebral toxoplasmosis: CT scan with contrast showing multiple ring enhancing lesions

© 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

© 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.

© 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.

ToxoplasmosisLymphoma
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