Sexual Health
A 54 year old man presents to the Emergency Department with a 2 week history of cough. He is known to be HIV positive and you are concerned about the risk of atypical pneumonia. HIV predominantly infects which type of cell?
Answer:
HIV causes immunodeficiency by preferentially infecting and destroying cells of the immune system, in particular the CD4 cells, a class of T lymphocytes which are also known as T helper cells.Human Immunodeficiency Virus
Infectious Diseases / Sexual Health
Last Updated: 12th February 2021
There are 2 main types of HIV — HIV-1 and HIV-2.
- HIV-1 is highly virulent and is found worldwide.
- HIV-2 is found mainly in West Africa but has also been reported in Portugal, France, and increasingly in India and South America
HIV causes immunodeficiency by preferentially infecting and destroying cells of the immune system, in particular the CD4 cells, a class of T lymphocytes which are also known as T helper cells.
Transmission
In a person infected with HIV, the virus is present in cell-containing bodily fluids, such as blood, semen, vaginal secretions, breast milk, amniotic fluid, pleural effusions, and cerebrospinal fluid.
Infected bodily fluid can transmit HIV:
- By sexual activity — through vaginal, anal, or oral sex (especially in the presence of oral disease such as ulceration or gingivitis).
- Vertically from mother to child — during pregnancy, childbirth, or through breastfeeding.
- By inoculation — via a contaminated needle, instrument, blood, or blood product; through direct exposure of mucous membranes or an open wound to infected bodily fluids; or by a human bite that breaks the skin.
In the UK, HIV infection is most prevalent among men who have sex with men and black-African heterosexual men and women. In the UK, the number of HIV infections acquired through injecting drug use and mother-to-child vertical transmission is low.
Risk factors
Risk factors for HIV infection include people who:
- Have a current or former partner who is infected with HIV, or is from an area with high HIV prevalence, or has a history of injecting drug use.
- Are men who have sex with men (MSM).
- Are female sexual contacts of MSM.
- Are from an area of high prevalence of HIV.
- Have had multiple sexual partners.
- Have a history of sexually transmitted infections, hepatitis B or hepatitis C infection.
- Have a history of injecting drug use.
- Have been raped.
- Have had blood transfusions, transplants, or other risk-prone procedures in countries without rigorous procedures for HIV screening.
- May have had an occupational exposure such as a needle stick injury.
Natural history
- Incubation period
- 2 - 4 weeks (all tests will be negative)
- HIV Seroconversion illness/Primary HIV infection (2 - 3 week duration)
- Symptoms of PHI develop in over 60% of people but can be mild and non-specific, including:
- Fever, sore throat, headache, malaise, lethargy, arthralgia, myalgia, and lymphadenopathy
- Features associated with immunosuppression, such as oral candidiasis or shingles
- Maculopapular rashes affecting the trunk, and orogenital or perianal ulceration
- Viral load is high in this stage and person is very infectious
- Symptoms of PHI develop in over 60% of people but can be mild and non-specific, including:
- Latent disease (asymptomatic stage)
- Duration of this varies widely between people with some progressing to AIDS (Acquired Immune Deficiency Syndrome) within 1–2 years ('rapid progressors') and others maintaining effective immune function more than 10 years later ('slow progressors')
- Disease progression
- Development of acquired immune deficiency syndrome (AIDS): defined as CD4 count < 200 cells/uL or development of AIDS-defining illnesses (opportunistic infections and malignancies)
Clinical features of long standing HIV infection
HIV should be considered if a person has had more than one of the following conditions or symptoms in the past 3 years, or has had conditions which are severe or resistant to treatment:
- Constitutional symptoms
- Fever, glandular fever-like illness, weight loss, sweats, lymphadenopathy
- Haematological conditions
- Anaemia, neutropaenia, thrombocytopaenia or other blood dyscrasias
- Genital conditions
- Severe or difficult-to-treat genital candida, severe genital herpes, severe genital warts
- Respiratory conditions
- Pneumocystis pneumonia (Pneumocystis jiroveci)
- Tuberculosis
- Bacterial lower respiratory tract infections
- Neurological and visual conditions
- Cryptococcal meningitis
- Cerebral toxoplasmosis
- Cerebral lymphoma
- Cytomegalovirus (CMV) retinitis
- Cancers
- Kaposi's sarcoma
- Non-Hodgkin's lymphoma
- Invasive cervical cancer
- Gastrointestinal conditions
- Oesophageal candidiasis
- Hepatitis B and hepatitis C infection
- Diarrhoea secondary to virulent organisms or opportunistic infections
- Oral conditions
- Oral candidiasis
- Aphthous ulcers
- Oral hairy leukoplakia
- Gingivitis
- Dental abscess
- Oral herpes simplex
- Skin conditions
- Fungal skin and nail infections, and pityriasis versicolor
- Viral infections such as herpes simplex, molluscum contagiosum, shingles, and warts
- Bacterial infections such as impetigo and folliculitis
- Seborrhoeic dermatitis and psoriasis
Diagnosis
- Arrange admission for urgent specialist assessment if there is concern about the possibility of a serious HIV-related condition.
- Pre-test counselling:
- Explain that it may be useful to offer an HIV test as part of several tests to investigate symptoms. Check their understanding of HIV and the significance of the window period.
- The window period is the time between becoming infected and antibodies appearing — HIV antibodies usually appear 4–6 weeks after infection but can take up to 12 weeks.
- Explain the importance of confidentiality and that the result will need to be recorded in medical records. Explain that a negative test result does not have to be disclosed in an insurance application, but a positive test result does if requested by an insurance company.
- Ensure that informed consent has been given for the test — written consent is not required.
- Explain the benefits of testing:
- If the test is negative, the person can be reassured and given advice on reducing the risk of HIV infection.
- If the test is positive, effective treatment can help prevent HIV-related illness and ensure that infection is not transmitted to contacts or in pregnancy.
- If the person is putting themselves at risk sexually or through injecting drug use, refer for further support or counselling to the local GUM clinic or substance misuse service.
- Explain that it may be useful to offer an HIV test as part of several tests to investigate symptoms. Check their understanding of HIV and the significance of the window period.
- Testing for HIV:
- Combined HIV antibody and p24 antigen tests
- The most commonly used assay tests for HIV-1, HIV-2, and the HIV p24 antigen simultaneously. This 'fourth generation' test detects the majority of people infected with HIV four or more weeks after exposure. If the test is positive, a second sample is required for confirmation. The test gives no indication of disease progression. A negative test result at least 4 weeks post-exposure can be reassuring but all people should be offered a further HIV test 12 weeks post-exposure to definitively exclude HIV infection.
- Point-of-care tests
- Point-of-care tests on samples from finger-prick or mouth swabs are used in some genito-urinary medicine (GUM) clinics, and results can be available within 1 hour. If the result is positive, a laboratory test should be done, as point-of-care tests are more likely to have false-positive results.
- Point-of-care tests may also be used in emergency situations such as when an unwell person presents to an Accident and Emergency department, or in community outreach testing and HIV screening pilots in primary care.
- Combined HIV antibody and p24 antigen tests
Monitoring
- Monitoring of HIV infection will be done in specialist clinics using the CD4 count and viral load.
- CD4 count
- The CD4 count reflects the degree of immunocompromise in people infected with HIV and indicates the risk of opportunistic disease.
- In a healthy person not infected with HIV, the CD4 count is usually greater than 500 cells/uL.
- CD4 counts are variable and can be reduced by common infections, so overall trends are more important than single values.
- People with CD4 counts below 200 cells/uL are most at risk of HIV-related opportunistic infections and cancers, but some may not have significant symptoms.
- CD4 counts are the main determinant of when prophylaxis for opportunistic infections and antiretroviral therapy (ART) is started.
- Viral load
- Viral load reflects rates of viral replication and is measured using a polymerase chain reaction (PCR) test.
- A rising viral load may indicate non-adherence to ART or resistance to one or more antiretroviral drugs.
- Viral load ranges from undetectable (less than 50 copies of viral genome/mL blood, to over a million copies/mL.
- The degree of viral replication is linked to the rate of CD4 decline and therefore disease progression — when viral load is suppressed through ART, CD4 counts recover and risk of HIV-related opportunistic infections and cancers declines.
Management
There is no cure for infection caused by the human immunodeficiency virus (HIV) but a number of drugs slow or halt disease progression. Antiretroviral therapy (ART) has had a huge positive impact on HIV-related morbidity and mortality, and aims to reduce viral load to undetectable levels by limiting viral replication, but is also associated with serious adverse effects. HIV mutates as it replicates so drugs are used in combinations of 3 or more to reduce drug resistance.
Treatment aims to prevent the mortality and morbidity associated with chronic HIV infection whilst minimising drug toxicity. Although it should be started before the immune system is irreversibly damaged, the need for early drug treatment should be balanced against the risk of toxicity. Commitment to treatment and strict adherence over many years are required; the regimen chosen should take into account convenience and patient tolerance. The development of drug resistance is reduced by using a combination of drugs; such combinations should have synergistic or additive activity while ensuring that their toxicity is not additive. It is recommended that viral sensitivity to antiretroviral drugs is established before starting treatment or before switching drugs if the infection is not responding. Treatment also reduces the risk of HIV transmission to sexual partners, but the risk is not eliminated completely; this risk and strategies to reduce HIV transmission should be discussed with patients and their sexual partners.
Antiretroviral drugs are classified into 5 groups depending on how they act:
- Nucleoside/tide reverse transcriptase inhibitors (NRTIs).
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
- Protease inhibitors (PIs).
- Integrase inhibitors (IIs).
- Entry inhibitors (EIs).
Adverse effects of ART include:
- Hypersensitivity
- Psychiatric — nightmares, sleep disturbance, mood or behaviour changes
- Hyperlipidaemia (common)
- Lipodystrophy (changes in the distribution of body fat) and lipoatrophy (loss of subcutaneous fat)
- Type 2 diabetes mellitus
- Fanconi’s syndrome (dysfunction of the proximal tubule), ureteric colic, renal and ureteric stones
- Lactic acidosis and hepatic toxicity
- Peripheral neuropathy
- Bone marrow suppression
- Pancreatitis
Post-exposure prophylaxis
- Occupational exposure to potentially HIV-infected bodily fluids
- See separate article on occupational needlestick injury
- Potential sexual exposure to HIV
- Exposure is a medical emergency and requires prompt treatment with a course of antiretroviral therapy (ART).
- Direct a person immediately to an HIV or genitourinary medicine (GUM) clinic or the Accident and Emergency department for consideration of post-exposure prophylaxis following sexual exposure (PEPSE) if:
- They are an uninfected sexual partner of a person known to have HIV, to prevent infection after sex without a condom or where the condom has split.
- They have had unprotected sex with a person in a high-risk group for HIV whose infection status is not known.
- PEPSE may be offered to victims of sexual assault depending on risk assessment (see separate article on sexual assault).
- PEPSE is only recommended when the person presents within 72 hours of exposure and should be given as early as possible.
- Needlestick injuries in the community
- People may present requesting post-exposure prophylaxis (PEP) following a needlestick injury from a discarded needle in the community.
- In general, PEP is not recommended for needlestick injuries in the community as it is usually not possible to determine:
- If the needle has been used and if so for what purpose.
- The HIV status of the source.
- The interval between needle use and exposure.
- If factors are present that may influence the probability of HIV transmission, seek expert advice from an HIV specialist.
- Human bites
- In general, PEP is not recommended following a human bite as although the risk of transmission following a bite is not known, it is likely to be extremely small.
- If factors are present that may influence the probability of HIV transmission, seek expert advice from an HIV specialist.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
