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HIV

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Overview

Human immunodeficiency virus (HIV) is a lentivirus belonging to the retrovirus subfamily and has two types HIV-1 and HIV-2. By infecting and destroying CD4+ T-cells, HIV causes immunodeficiency.

Transmission is via blood, blood products, sexual fluids, and breastmilk and may occur via:

  • Sexual transmission (e.g. unprotected sexual transmission)
  • Pregnancy (e.g. during delivery, breastfeeding)
  • Blood transfusion – blood is screened for HIV to reduce the risk
  • Intravenous drug use and sharing needles
  • Occupational exposure – such as needlestick injuries

In recent years, AIDS (acquired immunodeficiency syndrome) is less commonly used and ‘advanced HIV disease’ is used more instead.

Pathophysiology

Initial entry

HIV gains entry by attaching to the CD4 receptor and a co-receptor (CCR5 or CXCR4). Once in the cell, reverse transcriptase creates a DNA copy from the viral RNA (hence its identification as a retrovirus). RNA transcriptase is highly error-prone, resulting in a high rate of HIV mutation, increasing the risk of antiviral resistance.

Primary HIV infection (seroconversion)

In the first 10 days to 6 weeks, a flu-like illness occurs known as primary HIV infection (or HIV seroconversion illness). During this phase, the viral load is high and the person is highly infectious.

Asymptomatic phase.

Once the symptoms of primary HIV infection resolve, an asymptomatic stage begins. CD4+ cells recover and the viral load decreases, however, over time, CD4+ counts decrease and viral load increases gradually.

The duration of this phase can vary widely. Some people can progress to advanced HIV disease (or acquired immunodeficiency syndrome, AIDS) as quickly as 1-2 years (known as ‘rapid progressors’), whereas, in others, it can be as long as 10 years (‘slow progressors’).

Advanced HIV disease (also known as AIDS).

Advanced HIV disease (or AIDS) occurs when CD4+ cell counts are very low (<200 cells/mm3) and opportunistic infections or malignancies develop. These conditions are known as AIDS-defining illnesses.

Epidemiology

  • In 2018, around 103,800 people were living with HIV and around 7500 were unaware they had an infection. Of these people:
    • Around 49,800 (48%) were gay or bisexual men
    • Around 48,600 (47%) were heterosexual
    • Around 2300 (2%) were people who inject drugs 
  • In 2018 the proportion of AIDS-defining illnesses was as follows:
    • Pneumocystis pneumonia was the most common (37%)
    • Candidiasis (22%)
    • Tuberculosis (8%)
    • Kaposi’s sarcoma (8%) 

Risk Factors

Risk factors include:

  • High-risk sexual activity:
    • Unprotected anal or vaginal sex
    • Multiple sexual partners
    • High-risk sexual practices (e.g. chemsex)
    • Other sexually transmitted infections (STIs) including syphilis, Chlamydia, gonorrhoea, and herpes
    • Sex work
  • Sharing contaminated needles and intravenous drug use
  • Injections, transfusions, procedures involving unsterile cutting/piercing without HIV screening
  • Accidental needlestick injuries and occupational exposure
  • Living in an area with high HIV prevalence

Presentation

Suspecting HIV in general

Features that may suggest HIV as a likely include:

  • Common symptoms or infections that are unusually severe, prolonged, recurrent, or unexplained
  • Conditions associated with immunosuppression – such as candidiasis and shingles
  • Pyrexia and/or lymphadenopathy of unknown origin
  • Unexplained weight loss
  • The presence of risk factors

Primary HIV infection (seroconversion)

Lentiviruses have a long latent phase between infection and the development of symptoms. Features of primary infection tend to resemble infectious mononucleosis for up to 6 weeks. During this time, there is a rapid decline in CD4+ cells and an increase in viral load:

Other features can include hepatosplenomegaly, and neurological features (e.g. meningitis). 

Following this phase, people are asymptomatic for up to 10 years with a gradual fall in CD4+ count. Before the onset of an AIDS-defining illness, people may have constitutional symptoms.

Children and infants

Features that may be seen in infants include:

Features in children include:

  • Common infections that are recurrent, severe, persistent, or unexplained
  • Chronic diarrhoea
  • Shingles
  • Severe pneumonia
  • Tuberculosis
  • Unexplained lymphadenopathy
  • Any AIDS-defining condition

HIV: Associated Respiratory Conditions

Pneumocystis pneumonia (PCP)

Previously known as Pneumocystis carinii, Pneumocystis jirovecii is a fungus that can cause pneumocystis pneumonia (PCP), an opportunistic infection in people with HIV. PCP is the most common AIDS-defining illness and is often seen when the CD4+ count is <200 cells/mm3.

PCP can be life-threatening and difficult to diagnose as it is insidious and develops over weeks.

See Pneumocystis pneumonia for more. 

Tuberculosis

Tuberculosis is a common presenting condition in HIV and can be pulmonary or extrapulmonary. People may present with constitutional symptoms and cough.

See Tuberculosis for more.

HIV: Associated Neurological Conditions

Cerebral toxoplasmosis

Immunodeficiency can lead to the reactivation of a previous toxoplasmosis infection, which can cause cerebral lesions and present with:

A CT scan may show single or multiple ring-enhancing lesions with or without mass effect. It is managed using sulfadiazine and pyrimethamine.

Cerebral lymphoma

Cerebral lymphoma may develop which can present similarly to toxoplasmosis with features of elevated intracranial pressure, fever, and focal neurological deficits.

Its treatment may involve corticosteroids, chemotherapy, and brain irradiation. In some cases, surgery may be performed.

Sometimes toxoplasmosis can be difficult to distinguish from cerebral lymphoma. Thallium-201-chloride single-photon emission computed tomography (SPECT) and their appearance can be used to differentiate them:

  • Toxoplasmosis:
    • CT/MRI: ring or nodular enhancement
    • Thallium SPECT: negative
  • Cerebral lymphoma – 
    • CT/MRI: homogenous enhancement
    • Thallium SPECT: positive

Cytomegalovirus retinitis

Cytomegalovirus (CMV) may reactivate, leading to vision loss, which may present with:

  • Floaters – due to inflammatory cells in the vitreous
  • Flashing lights
  • Reduced vision and scotomas

Encephalitis

Encephalitis may occur due to CMV or HIV itself. A CT scan may show cerebral oedema.

Cryptococcus

Cryptococcus is the most common neurological fungal infection and can present:

  • Meningitis
  • Constitutional features – headaches, fever, malaise
  • Elevated intracranial pressure – nausea and vomiting, confusion, reduced consciousness focal neurological deficits (e.g. cranial nerve palsy)

Lumbar puncture results may show:

  • Elevated opening pressure and protein
  • Reduced glucose
  • High/normal white cell count – mostly lymphocytes
  • India ink staining is positive

A CT scan may show oedema and meningeal enhancement.

Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) describes cerebral demyelination due to the infection of oligodendrocytes by the JC virus, a virus that is present in more than half of people but does not cause infection if they are immunocompetent.

Features develop over weeks-months with features depending on the location of damage:

  • Behavioural changes
  • Cognitive impairment
  • Ataxia
  • Hemiparesis
  • Aphasia
  • Vision impairment (e.g. hemianopia)

A CT scan may show single/multiple lesions and an MRI may show demyelinating white matter lesions.

AIDS dementia complex

Also known as HIV encephalopathy, the HIV itself may damage cerebral cells causing features including cognitive impairment, behavioural changes, and motor impairment.

A CT may show cortical/subcortical atrophy.

HIV: Associated Renal Conditions

HIV-associated nephropathy

Although antiretroviral treatment can cause renal impairment, HIV itself also can. HIV-associated nephropathy (HIVAN) is a form of focal segmental glomerulosclerosis that can cause nephrotic syndrome. Features include:

  • Features of nephrotic syndrome
  • Normotension
  • Urea and electrolytes are elevated
  • An ultrasound may show enlarged, echogenic kidneys
  • A renal biopsy is diagnostic and shows focal/global capillary collapse

HIV: Associated Malignant Conditions

Kaposi’s sarcoma

Kaposi’s sarcoma is the most common tumour in HIV infection that is caused by human herpesvirus 8 (HHV-8). Tumours are found on the skin and oropharynx and in rare cases, they can infiltrate the gut or lungs which can be life-threatening.

Features include:

  • Dark purple/brown intradermal lesions on the skin or mucosa that may ulcerate
  • They tend to be painless
  • Respiratory involvement can cause haemoptysis and pleural effusion
  • Gastrointestinal involvement can cause abdominal pain, diarrhoea, nausea/vomiting, weight loss, and bowel obstruction.
  • Mouth lesions often affect the hard and soft palate, gingiva, and dorsal tongue

It can be managed with radiotherapy and resection.

Other cancers

HIV is associated with the development of lymphoma whose features can include constitutional symptoms, lymphadenopathy, hepatomegaly and splenomegaly.

It is also associated with the development of cervical cancer, which can present with abnormal vaginal bleeding or discharge. Abnormal cervical cytology may suggest an underlying HIV infection.

HIV: Associated Skin Conditions

Overview

As well as Kaposi’s sarcoma, HIV is associated with skin conditions that are unusually severe, recurrent, or resistant to treatment including:

  • Fungal infections of the skin and nails (e.g. pityriasis versicolor)
  • Bacterial infections – such as impetigo or folliculitis
  • Herpes simplex – particularly if ulcers are unusually large/persistent
  • Shingles – especially if more than 1 dermatome is affected
  • Seborrhoeic dermatitis and psoriasis
  • Molluscum contagiosum
  • Warts

HIV: Associated Oral Conditions

Oropharyngeal candidiasis

An infection of the mouth and oesophagus by Candida albicans may occur leading to:

  • Thick, white plaques on the buccal mucosa – these can be scraped off
  • Odynophagia and sore mouth

It is diagnosed clinically and managed with oral fluconazole.

Oral hairy leukoplakia

Oral hairy leukoplakia is associated with the Epstein-Barr virus and is nearly exclusively seen in people with HIV. This presents with a white patch that is corrugated/hairy on the tongue and occurs due to epithelial hyperplasia of the oral mucosa.

Gingivitis

Gingivitis is the inflammation of the gum tissue and may present with erythematous, swollen gum margins that are painful and bleed when brushing the teeth.

This occurs due to oral anaerobic bacteria and may be associated with necrotising gingivitis, where necrosis of the gums can occur, causing severe pain, haemorrhage, malodour, and a pseudomembrane.

Other related complications include periodontitis (inflammation of the connective tissue surrounding the teeth) and necrotising stomatitis (inflammation and necrosis of the tongue).

Other oral complications

Dental abscesses may occur, which can present with rapid severe tooth pain, an unpleasant taste in the mouth, fever, and malaise.

Aphthous ulcers may also occur.

HIV: Associated Gastrointestinal Conditions

Oesophageal candidiasis

An infection of the oesophagus by Candida albicans can cause oesophageal candidiasis which presents with:

It may be managed using fluconazole or itraconazole.

Diarrhoea

Diarrhoea is common in HIV. This may be due to HIV itself (HIV enteritis) or opportunistic infections including:

  • Cryptosporidium – the most common cause of diarrhoea in people with HIV:
    • It is a protozoan with an incubation period of around 7 days
    • A modified acid-fast (Ziehl-Neelsen) stain can identify red cysts associated with Cryptosporidium
  • Cytomegalovirus
  • Mycobacterium avium intracellulare – may have associated fever, sweating, abdominal pain, hepatomegaly and deranged liver function tests
  • Cytomegalovirus
  • Giardiasis

Hepatitis

Coinfection with hepatitis B or C is common and increases the risk of liver cirrhosis and hepatocellular carcinoma.

HIV: Other Associated Conditions

Genitourinary conditions

HIV should be considered if someone presents with severe, persistent, unusual, or recurrent genital including Candida, genital herpes, and genital warts.

Haematological conditions

HIV should be considered in a person with unexplained abnormal full blood count results such as neutropenia, anaemia, thrombocytopenia etc.

HIV and CD4 Counts

Overview

Different opportunistic infections and AIDS-defining illnesses can occur according to the CD4 count. In general:

  • CD4+ 200-500 cells/mm3: oral candidiasis, shingles, Kaposi’s sarcoma, oral hairy leukoplakia
  • CD4+ 100-200 cells/mm3: Cerebral toxoplasmosis, PML, PCP, AIDS dementia complex, Cryptosporidium infection
  • CD4+ 50-100 cells/mm3: oesophageal candidiasis, cryptococcal meningitis, primary cerebral lymphoma, aspergillosis
  • CD4+ <50 cells/mm3: CMV infection, Mycobacterium avium cellulare infection 

Diagnosis and Screening

Overview

HIV antibodies

HIV antibodies may not be present in early infection, however, they are present in most people at 4-6 weeks and over 90% at 3 months. They are screened for using an ELISA (Enzyme Linked Immuno-Sorbent Assay) test and a repeat test to confirm is done using an HIV-1/HIV-2 differentiation assay.

p24 antigen

The p24 antigen is a viral protein that can be found earlier as viral RNA rises in the blood. It is usually positive at 1-4 weeks after infection.

Combination testing

Combined p24 and HIV antibody testing are used for the diagnosis and screening of HIV:

  • If positive, another repeat confirmatory test is done

In asymptomatic people, testing should be done at 4 weeks post-exposure:

  • If negative, offer a repeat confirmatory test at 12 weeks

HIV Prophylaxis

Post-exposure prophylaxis

In general, the risk of HIV transmission depends on the type of incident (e.g. needlestick injury, sexual intercourse, bites etc.) and the viral load of the person with HIV.

The British HIV Association have produced guidelines on risk and post-exposure prophylaxis (PEP). Low-risk incidents such as bites (unless there is blood in the mouth of the biting person which breaks the skin and enters) do not require post-exposure prophylaxis.

If PEP is indicated, then combination antiretroviral therapy is started as soon as possible (ideally within 1-2 hours, but up to 72 hours) for 4 weeks. Combined testing is done at 12 weeks post-PEP.

Pre-exposure prophylaxis

Pre-exposure prophylaxis (PrEP) may be prescribed in specialist sexual health services to people who are at high risk of HIV transmission including:

  • HIV-negative men who have condomless sex with other men.
  • HIV-negative heterosexual men and women having condomless sex with partners who are HIV positive
  • HIV-negative trans women who are identified as being at elevated risk of HIV acquisition through condomless sex

Management

Overview

The management of HIV involves the use of a combination of antiretroviral drugs. They are now started as soon as someone is diagnosed with HIV rather than waiting for a CD4+ count of <200 cells/mm3.

Prognosis

  • People living with HIV who adhere and respond to treatment live near-normal lives
  • Early diagnosis and antiretroviral treatment are crucial for reducing mortality. Without treatment, the CD4+ cell count drops, eventually leading to AIDS-defining illnesses and death.

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