1 HIV infection
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- Introduction to HIV infection
- The spread of HIV
- Screening for HIV infection
- Clinical presentation of HIV infection if treatment has not been started
- Clinical stages of HIV infection
- Common complications of HIV infection
- WHO staging system for HIV infection in adults and adolescents (for reference)
- Case studies
When you have completed this chapter you should be able to:
- Define HIV infection and AIDS.
- Explain how HIV is transmitted between people.
- Appreciate why HIV infection is having a devastating effect on society.
- Confirm the clinical diagnosis of HIV infection.
- Describe acute seroconversion illness.
- Explain the asymptomatic and symptomatic phases of HIV infection.
- Describe the 4 clinical stages of HIV infection.
- Recognise the clinical signs of HIV infection.
Introduction to HIV infection
1-1 What is HIV?
HIV, the human immunodeficiency virus, is a virus which infects people for life.
Viruses are extremely small, very simple organisms which can only exist and multiply by invading and taking control of a plant or animal cell (the host cell). Viruses are responsible for many diseases such as influenza and the common cold. Unlike bacteria they are not killed by antibiotics. Viruses may be divided into many different groups. HIV belongs to a group of viruses known as retroviruses.
People infected with HIV are said to be HIV positive.
HIV is the human immunodeficiency virus.
- HIV was first identified in 1983 by a research group headed by Luc Montagnier working in the Pasteur Institute in Paris. HIV is a relatively new human virus which probably first appeared in the 1950s.
1-2 What are retroviruses?
They are a group of viruses which are unique in nature as they have a special enzyme called reverse transcriptase. This enzyme enables HIV to introduce its own genes into the nucleus of the host cell. The host cell is then instructed to produce millions of new copies of the virus. These are released into the bloodstream and can then infect other cells. Retroviruses usually cause long periods of silent infection before signs and symptoms of disease appear.
- Retroviruses contain an RNA genetic code. The enzyme reverse transcriptase allows HIV to make double-strand DNA copies of its single-strand RNA. The DNA copy is then inserted into the DNA of the nucleus in the host cell. Only retroviruses have this ability to make a DNA copy of their RNA code. Retroviruses are common and some cause cancers in animals.
HIV is a retrovirus.
1-3 What disease is caused by HIV?
HIV causes AIDS (Acquired Immunodeficiency Syndrome). Without treatment with antiretroviral drugs (ARVs), AIDS is a fatal condition.
HIV causes AIDS.
1-4 What is AIDS?
AIDS is a clinical syndrome (a group of signs and symptoms that occur together) which presents in people with advanced HIV infection (severe HIV disease). It can present in many different ways. The signs and symptoms of AIDS are usually due to secondary infections with a number of different organisms not commonly seen in HIV-negative people. People with AIDS are always HIV positive.
The terms ‘symptomatic HIV’ or ‘HIV disease’ are also used for patients who are clinically ill because of HIV infection. These patients may not yet be ill enough to be labelled as having AIDS.
A secondary infection is an infection that complicates an initial or primary infection. Bacterial or fungal infections (secondary infections) are common in patients with HIV infection (the primary infection).
1-5 How does HIV cause disease?
HIV invades and destroys the immune system by damaging the CD4 lymphocytes. As the CD4 cells play a very important role in the functioning of the immune system, HIV infection of CD4 cells damages the immune system, leading to failure of the immune system (immune deficiency). Therefore, HIV destroys more and more CD4 cells, and the body’s immune system becomes weaker and weaker.
The normal immune system protects the body against infection. Therefore, by killing CD4 cells, HIV weakens the immune system which is then no longer able to prevent infection by many viruses, bacteria, fungi and parasites.
HIV infection damages the immune system.
- About 10 billion copies of HIV are produced each day in infected people.
1-6 Are there different types of HIV?
Two types of HIV are recognised, HIV1 and HIV2. Most HIV infection in southern Africa is caused by HIV1, which has many subtypes (clades). The important subtype in Africa is subtype C. Subtype B is the most common subtype in the developed world.
The spread of HIV
1-7 Is HIV infectious?
Yes. HIV infection can be spread (transmitted) from one person to another.
1-8 How is HIV transmitted from one person to another?
The virus may be transmitted from one person to another by:
- Unprotected sexual contact (horizontal transmission). Body fluids such as vaginal and cervical secretions, semen and blood contain large amounts of HIV. HIV is not present in urine or stool, while very little is present in saliva.
- Crossing from a mother to her child during pregnancy, childbirth or during breastfeeding (vertical transmission).
- Using syringes, needles or blades which are soiled with HIV-infected blood. They may be shared by intravenous drug users or not correctly cleaned and then reused by health workers.
- Accidental needle-stick injuries.
- A blood transfusion with HIV-infected blood or other HIV-infected blood products such as factor VIII in haemophiliacs. This is very rare in South Africa, where all blood products are screened for HIV.
There is no evidence that HIV can be spread by mosquitoes, lice or bed bugs. In Africa, HIV is most commonly spread by heterosexual intercourse.
1-9 What forms of sexual contact may transmit HIV?
HIV is almost always transmitted by penetrative sexual intercourse (heterosexual or homosexual). However, all forms of oral sexual contact (mouth to vagina or mouth to penis) can also result in infection, although the risk is less. Deep kissing rarely transmits HIV, unless mouth sores (ulcers) are present. HIV cannot penetrate intact skin but may infect through open skin sores, cuts and abrasions, or mucous membranes. The highest risk of sexual transmission for both men and women is during anal intercourse. The thin, friable rectal mucosa is easily damaged during anal intercourse, which increases the risk of infection. The presence of any other sexually transmitted infection will also increase the risk of HIV transmission. Physical sexual abuse and rape may also result in HIV infection.
In South Africa, HIV is usually spread by sexual intercourse.
1-10 Can you become infected with HIV during normal social contact?
No. Family and friends of an HIV-infected person do not become infected except by sexual contact or through open sores, cuts and abrasions when they come into contact with the infected person’s blood. HIV is not transmitted by close social contact such as touching, holding hands, hugging and social kissing. HIV is also not spread by coughing, sneezing, swimming pools, toilet seats, sharing cooking, drinking and eating utensils or by changing a nappy. However, any bleeding, such as nose bleeds, may spread HIV.
1-11 How can the sexual spread of HIV in the general public be reduced?
There are many factors in the ‘HIV Prevention Toolbox’ to help reduce the spread of HIV. These include:
- ‘A’ – Abstinence (no sex) and delay in sexual debut (first-time sex). Abstinence is the most effective way to stop the sexual spread of HIV but the reality is that most people do not practice abstinence.
- ‘B’ – Be faithful to 1 partner (reduce the number of sexual partners). The reduction in number of sexual partners, especially if both partners are faithful to each other (mutual monogamy), has resulted in declining HIV prevalence in some countries.
- ‘C’ – Use a condom (especially when not being faithful to 1 partner). Condoms, used consistently, are very effective at reducing the sexual transmission of HIV.
- ‘D’ – Drugs (HIV medicines called antiretrovirals). Pre- exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) with ARVs. PrEP is taken before possible exposure to HIV, e.g. before sex, while PEP is taken after exposure to HIV e.g. after rape. Both PrEP and PEP are very effective in preventing HIV transmission.
- ‘Treatment for prevention’ – If an HIV positive person is taking their ARVs daily the amount of virus in their blood decreases. As a result they are no longer able to transmit HIV to another person.
- Male circumcision (removal of the penis foreskin) – This reduces the chances of the male getting HIV but does not reduce the risk of transmitting HIV to his partner.
- Voluntary HIV testing – When a person knows their HIV status they may be more cautious in their sexual behaviour and thereby reduce the spread HIV.
There are many ways of preventing the sexual spread of HIV.
1-12 Can you have HIV infection and not be ill?
Yes. An adult person is usually infected with HIV for years before becoming ill. Therefore, most people infected with HIV are clinically well (asymptomatic) for many years.
1-13 Can an HIV-infected person who is well transmit the virus?
Yes. HIV is frequently transmitted by people who appear to be clinically well but are infected with HIV. This is the great danger of HIV infection as many infected people do not know that they have HIV. They are also unaware that they may transmit HIV to another person.
1-14 How common is HIV infection?
According to the World Health Organization, nearly 37.9 million people worldwide were living with HIV at the end of 2018. In the same year an estimated 7.7 million South Africans were living with HIV while about 30% of all pregnant women in South Africa were infected with HIV. KwaZulu–Natal province had the highest antenatal prevalence of 41%. In some antenatal clinics, more than 50% of pregnant women were HIV positive. This has increased from less than 2% in 1990.
1-15 How often does HIV infection cause death?
It is estimated that 25% of deaths in South Africa in 2018 were AIDS related. This huge decrease from 48% in 2006 is due to the roll-out of ARVs. Still, many of these deaths could be prevented with the correct treatment. Without antiretroviral treatment (ART) most people with HIV infection will eventually die of AIDS.
1-16 Is the HIV epidemic in South Africa still expanding?
No. There has been a reduction in the number of deaths due to AIDS as well as a reduction in the number of new HIV infections. Since 2010, there has been a 50% decrease, from 140 000 deaths to 71 000 deaths annually. In addition, the number of new HIV infections fell from 390 000 to 240 000 annually in the same period. However the number of people living with HIV has increased as many are not dying but remain healthy on treatment with ARVs.
1-17 What is the risk of HIV crossing from an infected mother to her infant?
Without HIV prophylaxis with ARVs the risk of HIV crossing the placenta during pregnancy is 5%, while the risk of HIV infecting the infant during labour and vaginal delivery is 15%. The overall risk during pregnancy, labour and vaginal delivery without ARVs is therefore 20%.
Without HIV prophylaxis there is an additional risk of 15% if the mother practises mixed breastfeeding (breast milk plus other liquids and solids) for 2 years. The total risk of mother-to-child transmission (MTCT) in these breastfed infants is therefore 35%. The risk of breast milk transmission is 5% for the first 6 months, 5% for the second 6 months and 5% for the second year. With exclusive breastfeeding (breast milk only) for 6 months, the risk is much lower.
Without the use of antiretroviral drugs the overall risk of HIV transmission in breastfeeding mothers is 35%.
1-18 How can the risk of mother-to-child infection be reduced?
The most effective method is to use ARVs. With the prevention-of-mother-to-child-transmission (PMTCT) programmes, mother-to-child transmission of HIV in South Africa has been reduced to less than 2%.
- Giving all HIV-positive pregnant women lifelong antiretroviral therapy, starting from their first antenatal visit.
- Promoting exclusive breast feeding for the first 6 months. Avoid mixing breastfeeding with any other feeds. Feeding with formula, or even giving additional water, results in greater HIV transmission. Exclusively breastfed babies do not need additional water as they get all their water requirements from the milk. Complementary feeding can start at 6 months, with breastfeeding continuing until 12 months.
- Giving daily nevirapine to all HIV exposed infants for 6 weeks after birth regardless of feeding choice. After 6 weeks, stopping or continuing nevirapine will depend on feeding choice (formula vs exclusive breast feeding) as well as the mother’s duration of antiretroviral treatment and viral load.
Since 2016, South Africa has implemented the universal test and treat strategy. All HIV-positive people should be offered antiretroviral treatment. With the roll-out of the PMTCT programme, the number of HIV-infected children should be greatly reduced.
The use of prophylactic antiretroviral drugs dramatically reduces the risk of mother-to-child transmission.
1-19 What is the impact of HIV infection on society?
The epidemic of HIV infection has had a devastating impact on society in South Africa and other countries in sub-Saharan Africa. At the peak of the AIDS epidemic in South Africa, the average life expectancy fell to around 45 years but has increased to around 64 years following the roll out of ART.
In Africa, most people with HIV infection are female and most are from poor communities. This has a massive effect on families and increases the risk of childhood under-nutrition and death, even in HIV-negative children. As a result of the number of deaths, ill people and homeless children, HIV infection has had an enormous social and financial impact on all communities, and has placed a strain on the health services.
Every effort must be made to prevent women becoming infected with HIV. This is the most effective way of preventing HIV infection in children.
Screening for HIV infection
1-20 How is the clinical suspicion of HIV infection confirmed?
By detecting either antibodies to the virus or identifying part of the virus in the blood.
1-21 Should people be counselled before HIV testing?
People must be informed and counselled before blood tests to confirm or exclude HIV infection are done. It should be documented that the person consents to screening. It is considered unethical practice to perform HIV screening tests without the person’s permission. HIV screening is very important as it is the ‘gateway to care’.
1-22 What tests are available to screen for HIV infection?
A number of tests are available to screen people for HIV infection but they fall into 2 broad groups:
- Tests that look for the body’s reaction to HIV (antibodies)
- Rapid test
- ELISA (Enzyme-Linked Immunosorbent Assay) test
- Tests that look for HIV itself:
- PCR (Polymerase Chain Reaction) test
- P24 antigen test
See skills chapter 6A for how to do a rapid test.
- HIV culture and testing for other HIV antigens can also be done. These are expensive tests and are only used in research or in cases where the diagnosis of HIV infection is difficult. The Western blot test is the most accurate test for detecting virus antibodies, and is used in the laboratory to make a diagnosis in difficult cases with conflicting results with the ELISA or rapid test.
1-23 What are the rapid and ELISA screening tests?
These are commonly used blood tests to screen well people for HIV infection and also to confirm HIV infection in people who have symptoms and signs. Both are cheap and very accurate, and become positive when antibodies to HIV are present. These tests detect whether antibodies are being produced to HIV. They are highly reliable and accurate. The rapid test is most commonly used to screen for HIV infection. Kits are available to perform the rapid test at a clinic (on-site).
The rapid test is the most common method used to screen people for HIV infection.
- Both ELISA and rapid tests are 99% accurate if performed correctly and are confirmed with a second test using a kit from another manufacturer.
1-24 How is the ELISA test done?
The ELISA test is done by a laboratory on a sample of venous blood taken from the person. 1 to 2 ml of clotted blood is needed. The laboratory should provide a result within 24 hours. The result is either positive or negative. The disadvantage of the ELISA test is that it cannot be done at a clinic and requires someone to be able to take blood.
1-25 How is the rapid test done?
The great advantage of the rapid test is that it can be done on a drop of blood in a clinic and blood does not have to be sent to a laboratory. It can also be done by a trained lay person because it only requires a drop of blood that can be obtained by a finger-prick. There are a number of manufacturers who provide rapid tests. They are very similar, but not exactly the same.
- If the first rapid test is negative, accept that the person is HIV negative.
- If 2 rapid tests on different kits are positive, accept that the person is HIV positive.
- If the first test is positive and the second is negative, send blood to the laboratory for an ELISA test to decide whether the person is HIV positive or negative.
Rapid tests are very accurate but there is a very small chance of a false positive result (the test is positive but the patient is not infected with HIV). This is why positive tests are repeated. The repeat test must be done with a kit from another manufacturer, or with another type of test.
False negative results (a negative result when the person is actually infected with HIV) are extremely unlikely. So one negative test is enough to confirm a negative result.
1-26 What is the PCR test?
This test determines whether there is DNA from the HIV (genetic material from the nucleus of the virus) present in the lymphocytes in the person’s blood. The PCR test is very useful in screening infants younger than 18 months for HIV infection as the rapid and ELISA tests are unreliable to confirm HIV infection at this time, due to the possible presence of maternal antibodies.
- The HIV DNA PCR test (qualitative) detects the presence of the virus within cells while the HIV RNA PCR test (quantitative) measures the amount of virus in the blood (viral load).
The PCR test detects very small amounts of HIV material in the blood.
1-27 What is the p24 antigen test?
The p24 antigen is part of the virus and the p24 antigen test detects this HIV material in the blood. The ultrasensitive p24 antigen test is very accurate.
1-28 When do these tests become positive if a person is infected with HIV?
They may become positive as early as 2 weeks after infection, but most are reliable from 6 weeks after infection.
1-29 What is the window period?
This is the period of time between infection and when the test becomes positive. During this time the test may give a false-negative result (the patient is infected with HIV but the test is still negative). For most tests, the window period lasts up to 6 weeks. Rarely, the window period may be longer, up to 3 months. With new, highly sensitive tests the window period is shortening.
1-30 What is the CD4 count?
CD4 cells are lymphocytes that play a very important role in the normal functioning of the immune system. HIV attaches to CD4 cells and kills them. As a result, the number of CD4 cells gradually falls as the HIV infection progresses, and more and more CD4 cells are killed. Therefore the CD4 count is the best measure of the degree that HIV has damaged the immune system. The normal CD4 count in a healthy adult is above 500 cells/µl.
The CD4 count measures the degree of damage done by HIV to the immune system.
- A low CD4 count must not be used to diagnose HIV infection as there are other causes of reduced CD4 cells.
1-31 What is the viral load?
The viral load is a measure of the amount of HIV in the blood. The higher the viral load, the faster the HIV is multiplying. A high viral load indicates that there is a lot of HIV in the blood (and other body secretions). Viral load is usually expressed as RNA copies/ml.
The viral load is a measure of the amount of HIV in the blood.
Clinical presentation of HIV infection if treatment has not been started
1-32 What are the three phases of HIV infection?
The natural history of untreated HIV infection can be divided into 3 phases:
- Acute seroconversion illness (which only occurs in 50% of people)
- The latent, silent, asymptomatic phase
- The chronic disease when HIV infection becomes symptomatic.
1-33 What is acute seroconversion illness?
In response to infection with HIV, the immune system produces antibodies against the virus. Unfortunately these antibodies fail to kill all the HIV. At the time that HIV antibodies appear in the blood (seroconversion) about 50% of people develop a flu-like illness which lasts a few days or weeks. Acute seroconversion illness presents 2 to 6 weeks after infection with HIV.
During acute seroconversion illness the viral load is very high and the CD4 count may be temporarily depressed. The antibody screening tests for HIV may still be negative at the time of acute seroconversion illness, and only becomes positive a few weeks later.
Infection with HIV may cause acute seroconversion illness.
- Patients who develop severe acute seroconversion illness usually progress to AIDS faster than those who are asymptomatic while seroconverting. They should be closely followed up.
1-34 What are the common features of acute seroconversion illness?
The common features of acute seroconversion illness are:
- General tiredness
- Cough or sore throat
- Muscle or joint pains
- Nausea, vomiting or diarrhoea
- Enlarged lymph nodes (lymphadenopathy)
- A measles-like rash
- Oral or genital ulcers
The above signs and symptoms are similar to those found in glandular fever (infectious mononucleosis) and therefore are not only present in HIV acute infection.
- Some people also develop neurological complications such as meningitis, encephalitis or neuropathy. Typically the lymphocyte and CD4 counts are low during the acute illness.
Acute seroconversion illness is often the first sign of HIV infection.
1-35 Are people with seroconversion illness infectious to others?
Yes, during the first few weeks of HIV infection, especially if the person develops seroconversion illness, large amounts of virus are present in the blood and other body fluids, and the person is very infectious to others.
People are very infectious during the first weeks of HIV infection.
1-36 How are patients with acute seroconversion illness managed?
The immediate management of patients is symptomatic with antipyretics (e.g. paracetamol) for fever. Patients in the acute phase of HIV should also be urgently started on ARVs.
- Antiretroviral treatment in the acute phase has been shown to reduce the viral set point (viral load after the acute seroconversion illness) and will also reduce transmission during this highly infectious phase.
1-37 What is the latent phase of HIV infection?
HIV infection and seroconversion are followed by a latent period when the person feels well. During this phase many people are not aware that they are HIV infected. Although there are usually no, or few, clinical signs during the latent phase of HIV infection, generalised lymphadenopathy is common.
During the latent phase the viral load is usually relatively low and the CD4 count is normal or only mildly depressed.
Most people with asymptomatic HIV infection are not aware that they have been infected with HIV.
1-38 How long does the latent phase last?
Usually this silent, asymptomatic period lasts 5 to 10 years in adults but it may last for as long as 15 years before the signs of AIDS appear (‘slow progressors’). Occasionally, HIV-infected people progress rapidly to AIDS (‘fast progressors’).
The asymptomatic latent phase usually lasts 5 to 10 years in adults.
1-39 What is symptomatic HIV infection?
When patients who have been clinically well during the latent (asymptomatic) phase of HIV infection become ill, they are said to have symptomatic HIV infection. The symptoms and signs of symptomatic HIV infection only present when the immune system is no longer able to protect the person from a wide range of viral, bacterial, fungal and parasitic infections (opportunistic infections).
Clinical illness only occurs late in the course of HIV infection.
1-40 When is symptomatic HIV infection called AIDS?
Once patients develop severe opportunistic infections or malignancies typically associated with HIV infection (WHO stage 4). This only occurs when the immune system has been severely damaged. Patients who are generally well or only mildly ill with HIV infection do not yet have AIDS.
1-41 How do the viral load, antibody levels and CD4 count change during the course of HIV infection?
The level of virus in the blood (viral load) rises very rapidly within weeks of infection due to the extremely high rate of viral multiplication. This temporarily depresses the CD4 count. The production of antibodies increases in response to the HIV infection. Antibodies, together with CD4 cells, attempt to control the amount of virus in the body and the levels of HIV in the blood decreases. Eventually (within 6 months) a balance is reached between the production and destruction of HIV. This is known as the viral set point.
With the onset of symptomatic HIV infection (constitutional symptoms) the CD4 count starts to falls and the viral load increases and becomes very high with AIDS (opportunistic infections).
The level of virus in the blood is very high soon after infection and again with the development of AIDS.
- A high viral set point carries a poor prognosis of rapid progression to AIDS, as it indicates failure by the immune system to control massive multiplication of HIV.
Figure 1-1: The changes in viral load, CD4 count and clinical features of HIV infection
1-42 What clinical signs suggest the patient has HIV infection?
- Unexplained weight loss
- Unexplained fever or night sweats
- Generalised lymphadenopathy
- A variety of skin rashes
- Mouth infections such as oral candidiasis
- Chronic diarrhoea
- Repeated respiratory infections or chronic cough
- Signs of opportunistic infections and other HIV-related illnesses such as malignancies
Often painless, generalised lymphadenopathy in an otherwise healthy person is the first clinical sign of HIV infection.
Clinical stages of HIV infection
1-43 What is the natural progression of HIV infection?
The progression of early to advanced HIV infection usually follows a recognisable pattern which depends on the degree of damage to the immune system. The progression of HIV infection has been divided into 4 clinical stages by the World Health Organisation (WHO). Patients advance through stages 1 to 4 as their CD4 count falls.
The clinical signs become worse and the CD4 count falls as patients progress from stage 1 to stage 4 HIV infection.
See the WHO staging system for HIV infection in adults and adolescents at the end of this chapter.
1-44 What are the clinical signs of stage 1 HIV infection?
Patients with stage 1 HIV infection are well and asymptomatic but almost all have persistent, generalised lymphadenopathy, especially in the neck, axilla and groin. Acute seroconversion illness is also included in stage 1. Therefore, stage 1 starts at the time of infection.
People with stage 1 HIV infection are generally well.
1-45 What are the clinical signs of stage 2 HIV infection?
Patients with stage 2 HIV infection have repeated minor clinical problems. Skin rashes and minor mouth problems are very common. Often there is some weight loss (less than 10%) and mild diarrhoea can be a problem. Patients with these early stages of HIV infection can usually continue their daily activity.
Patients with stage 2 HIV infection have repeated minor clinical problems.
1-46 What are the features of stage 3 HIV infection?
Common features are unexplained weight loss (more than 10%), fever, oral candidiasis and diarrhoea. Pulmonary TB and severe bacterial infections indicate stage 3 infection. These patients feel generally unwell and are no longer able to continue with their usual daily activities. Most of these patients will improve if their opportunistic infections are treated.
Pulmonary TB and serious bacterial infections are common in patients with stage 3 HIV infection.
1-47 How would one recognise a patient with stage 4 HIV infection?
Marked weight loss continues and many patients are bedridden. Severe opportunistic infections such as oesophageal candidiasis, extrapulmonary TB, pneumocystis pneumonia, cryptococcal meningitis and toxoplasmosis are common. Anaemia and malignancies associated with HIV infection are also common. Patients with stage 4 disease are regarded as having AIDS. Response to ART is usually good. Without treatment many will die within months.
Serious opportunistic infections are common when stage 4 HIV infection (AIDS) is reached.
1-48 What are the features of terminal AIDS?
Additional opportunistic infections such as CMV retinitis and avium TB can occur. Severe wasting and dementia are common. These patients are seriously ill, usually with a CD4 count below 50 cells/µl. Response to ART may be poor as the immune system has been very seriously damaged by HIV. Without treatment most patients rapidly die.
Common complications of HIV infection
1-49 What is an AIDS-defining illness?
A serious clinical condition which is very uncommon in HIV-negative people and yet seen commonly in patients with advanced HIV infection. Severe opportunistic infections and malignancies in HIV-positive patients are AIDS-defining illnesses. Common AIDS-defining infections include oesophageal candidiasis, and severe infections, such as meningitis, with pneumocystis, cryptococcus and toxoplasmosis.
1-50 Is pulmonary tuberculosis an AIDS-defining illness?
Although pulmonary TB is common in patients with HIV infection, and indicates stage 3, it also occurs in HIV-negative people and it is therefore not an AIDS-defining infection. In contrast, extrapulmonary TB is rare in HIV-negative people and is therefore an AIDS-defining illness.
1-51 What conditions of the mouth are common with HIV infection?
The mouth and tongue are commonly affected when the immune system is damaged by HIV infection.
- The commonest mouth condition is oral candidiasis (thrush).
- Oral hairy leucoplakia. This is usually asymptomatic and painless, and presents as multiple, vertical white stripes along the side of the tongue. Its presence indicates immune depression.
- Aphthous ulcers. These are very painful, shallow ulcers that can occur anywhere in the mouth.
- Herpes simplex ulcers may also affect the mouth and are also painful.
- Gum infections around the base of the teeth (gingivitis) which may cause pain and bleeding.
- Kaposi’s sarcoma.
- Oral hairy leucoplakia is due to infection with the Epstein-Barr virus while Kaposi’s sarcoma is a malignancy caused by a herpes virus (Herpes 8).
Severe oral infections which prevent the patient eating and drinking, and do not improve in a few days, may lead to further weight loss, dehydration and under-nutrition. These patients should be referred for specialist care.
1-52 What skin rashes are commonly seen in patients with HIV infection?
Many different skin rashes are seen in HIV-infected patients and a skin rash may be one of the earliest signs of a depressed immune system:
- Pruritic papular eruption (PPE or ‘itchy bump disease’)
- Seborrhoeic dermatitis
- Fungal infections of the skin, hair and nails
- Molluscum contagiosum
- Impetigo and folliculitis
- Severe, extensive scabies
Rashes may also be due to drugs used in ART (e.g. nevirapine or efavirenz) or drugs used to treat opportunistic infections (e.g. co-trimoxazole). Drug reactions are more common in HIV-infected patients than in people who are not HIV infected.
1-53 What is characteristic of rashes in HIV-positive patients?
Rashes are often severe, chronic or recurrent, and respond poorly to standard treatment. Rashes frequently are atypical and usually do not resolve spontaneously. Previous rashes may become worse with the development of HIV infection, e.g. psoriasis, acne and eczema. With ART most rashes disappear.
1-54 What is pruritic papular eruption (PPE)?
This is very common in patients with HIV infection and presents with a severe itch and scattered pigmented papules (bumps), especially on the trunk and limbs (‘itchy bump disease’). It is difficult to treat and responds poorly to topical steroids and anti-itch agents. The rash slowly resolves with ART.
1-55 What is wasting disease?
Before the advent of ART, this was a common presentation of AIDS in patients in Africa. Weight loss is severe and associated with chronic diarrhoea. The patients feel weak and have fever. All patients with unexplained weight loss must be screened for HIV infection. Urgent ART is needed.
All patients with unexplained weight loss must be screened for HIV infection.
- Severe wasting is due to anorexia, diarrhoea, malabsorption and infections as well as oral conditions which make eating painful (e.g. thrush or herpes).
1-56 What malignancies are associated with AIDS?
Some forms of cancer occur more frequently in patients with AIDS. Viral infections and a damaged immune system are probably the cause. Of interest is that only some cancers are more common in AIDS patients. However, the progression of other cancers common in the general population is more rapid in AIDS patients. Cancers more common in patients with AIDS are:
- Kaposi’s sarcoma
- Non-Hodgkin’s lymphoma
- Cervical cancer
Patients with any of these cancers must be tested for HIV infection.
Kaposi’s sarcoma, non-Hodgkin’s lymphoma and cervical cancer are more common in patients with AIDS.
1-57 What is Kaposi’s sarcoma (KS)?
This is the most common cancer complicating AIDS.
Kaposi’s sarcoma usually presents with painless, multiple pink or purple patches in pale skin and brown or black patches in darker skin, or nodules (bumps) on the skin, especially the face, trunk and legs. The mouth may also be involved, especially the hard palate. The prognosis is poor in advanced cases when organs such as the gut, lungs and lymph nodes are affected (visceral Kaposi’s sarcoma). Non-visceral (skin) Kaposi’s sarcoma is usually not life-threatening, but can become extensive and have an unacceptable appearance. The patches and nodules often improve with ART. All patients with Kaposi’s sarcoma should be fast tracked and started on ART within 1 week of presenting to the clinic. Mild cutaneous KS may respond to ART alone while extensive KS requires chemo or radiotherapy. All patients with extensive skin lesions, oral lesions or signs of disseminated KS should be referred to a KS or specialist clinic within 2 weeks of starting ART.
Kaposi’s sarcoma presents with purple or brown skin patches or nodules.
- Kaposi’s sarcoma is associated with the Human Herpes 8 virus which may be sexually transmitted.
1-58 What is non-Hodgkin’s lymphoma?
This is the second commonest cancer in AIDS patients. Non-Hodgkin’s lymphoma is a group of different types of lymphoma which often progress rapidly. Therefore, early diagnosis and treatment are important. Lymphoma usually presents with large firm lymph nodes at 1 or more sites, or abdominal masses together with weight loss and unexplained fever. Sites other than lymph nodes can be involved, especially the brain, liver, bone marrow and gut. Non-Hodgkin’s lymphoma of the brain may present with a wide range of neurological conditions including headaches, convulsions, confusion and memory loss. Any patient with a suspected lymphoma must be referred for investigation and treatment. The prognosis is usually poor.
Lymphoma of the brain may present in AIDS patients with a wide range of neurological signs.
- Most lymphomas in AIDS patients are of B cell origin and associated with Epstein-Barr virus infection.
1-59 What is the presentation of cervical cancer?
Cervical cancer is common in women with AIDS. In the early stages there are usually no symptoms or signs. Therefore all HIV-positive women must have a PAP smear every 3 years. Cervical inspection for cancer can be done more frequently.
All HIV-positive women must be screened regularly for cervical cancer.
- The human papilloma virus, which is associated with cervical cancer, is sexually transmitted and more common in HIV-positive women.
1-60 What neurological conditions are associated with AIDS?
Many neurological complications are seen in patients with AIDS. Neurological problems may also be due to drug side effects (e.g. peripheral neuropathy with isoniazid (INH)).
- HIV encephalopathy
- Cryptococcal meningitis
- Bacterial meningitis
- Tuberculous meningitis or tuberculoma
- Non-Hodgkin’s lymphoma
- The spinal cord, peripheral nerves and muscles can also be involved.
1-61 What are HIV-associated neurocognitive disorders (HAND)?
HIV infects the brain early in the course of HIV disease. Signs of HIV-associated neurocognitive disorders (previously called HIV encephalopathy) usually develop slowly and become more obvious when the patient has AIDS, especially in the advanced stage. HAND may present at various stages of severity and is classified as:
- Asymptomatic Neurocognitive Impairment (ANI) if there is impairment in cognitive function (memory, thinking and understanding), but everyday functioning is not affected.
- Mild Neurocognitive Disorder (MND) if there is impairment in cognitive function and mild interference in everyday functioning.
- HIV-associated Dementia (HAD).
Common signs of HAND are:
- Poor concentration and short-term memory loss, eventually leading to dementia.
- Personality changes with depression, apathy, withdrawal or irritability.
- Weakness, tremors or clumsiness.
Often there are no obvious abnormalities on examination of the central nervous system early in the disease. The worsening of HAND can be slowed with ART.
- CT and MRI scans with HAND reveal cortical atrophy. In contrast, scans in progressive multifocal leukoencephalopathy (PML) due to Creutzfeldt-Jakob infection show areas of white matter demyelination.
WHO staging system for HIV infection in adults and adolescents (for reference)
Clinical stage 1
- Seroconversion illness
- Asymptomatic infection
- Persistent generalised lymphadenopathy
- Normal daily activity
Clinical stage 2
- Weight loss up to 10%
- Minor oral problems (recurrent mouth ulcers)
- Skin rashes
- Recurrent upper respiratory tract infections
- Herpes zoster (shingles)
- Symptomatic, but daily activity normal
Clinical stage 3
- Weight loss of more than 10%
- Chronic diarrhoea for more than 1 month
- Prolonged fever for more than 1 month
- Oral candidiasis
- Oral hairy leucoplakia
- Pulmonary tuberculosis
- Severe bacterial infection (e.g. meningitis, pneumonia)
- Bedridden for less than 50% of the day in the past month
- Unexplained anaemia (haemoglobin level below 8 g/dl), and or neutropenia (neutrophil count below 500/mm³) and/or thrombocytopenia (platelet count below 50 000/ mm³) for more than 1 month
Clinical stage 4 (AIDS)
- HIV wasting syndrome
- Pneumocystis pneumonia
- Oesophageal candidiasis
- Toxoplasmosis of the brain
- Cryptococcal meningitis
- Diarrhoea due to Cryptosporidiosis or Isosporiasis
- Cytomegalovirus (CMV) disease
- Extrapulmonary TB
- Chronic or disseminated herpes simplex
- HIV encephalopathy
- Recurrent pneumonia
- Kaposi’s sarcoma, lymphoma or invasive cervical cancer
- Confined to bed for more than 50% of the day
Additional clinical criteria indicating stage 4 disease
- Idiopathic thrombocytopenic purpura (ITP)
- Thrombotic thrombocytopenic purpura (TTP)
- Autoimmune haemolytic anaemia
- HIV-associated nephropathy
- HIV-associated cardiomyopathy
- Severe HIV neuropathy or HIV myelopathy
- Refractory apthous ulceration
- All malignancies (unless early malignancy that is surgically resectable with low relapse risk)
- Multiple drug resistant tuberculosis (MDR TB) HIV-associated vasculopathy
- Diffuse infiltrative lymphocytosis syndrome (DILS) with severe symptoms
- Acute inflammatory demyelinating polyneuropathy (AIDP)/chronic inflammatory demyelinating polyneuropathy (CIDP) non-responsive to immunomodulatory therapy
- These patients should be initiated on ART following consultation with an infectious disease/antiretroviral treatment unit specialist or specialist in these listed pathologies.
Case study 1
A healthy pregnant woman is found to be HIV positive. She asks how she probably became infected and whether HIV infection is common in pregnant women. She asks the nurse whether she will pass HIV on to her infant.
1. How is HIV usually transmitted in South Africa?
By penetrative heterosexual vaginal intercourse. The risk of HIV transmission is highest with anal intercourse in both men and women. The risk of HIV infection is much less with oral sexual contact. Kissing is probably safe.
2. Can HIV be spread by normal social contact?
No. HIV is not spread by touching, holding hands, hugging, coughing, sneezing, using swimming pools, toilet seats or sharing cooking, drinking and eating utensils.
3. Can a person with HIV infection appear perfectly healthy?
Yes. Many people feel well without any clinical signs in spite of having asymptomatic HIV infection for many years (the latent phase).
4. Are they infectious during this time?
Yes. The danger is that many infectious people who feel well do not know that they have HIV infection.
5. How common is HIV infection in pregnant women in South Africa?
By 2013, almost 30% of pregnant women attending state antenatal clinics were HIV positive. This has increased from less than 2% in 1990.
6. What is the risk that this woman will pass HIV to her infant?
With a vaginal delivery and no antiretroviral prophylaxis, the risk of HIV transmission is 20%. The additional risk of mixed breastfeeding is 15%. With antiretroviral prophylaxis consisting of triple therapy for the mother during pregnancy and breast feeding and nevirapine for the child during breast feeding the overall risk is less than 2%.
Case study 2
A young woman presents with fever, a sore throat, enlarged lymph nodes and a rash. She also feels generally unwell.
1. Could these signs and symptoms be due to HIV infection?
Yes. The presentation is typical of the acute seroconversion illness which occurs in over 50% of HIV infected people. This condition usually presents 2 to 6 weeks after HIV infection and may be misdiagnosed as glandular fever.
2. Should she be offered antiretroviral drugs?
Yes. Since 2016, South Africa has implemented the universal test and treat strategy. All HIV-positive people should be offered antiretroviral treatment. She should also be given symptomatic treatment (e.g. paracetamol for fever).
3. How can the clinical suspicion of HIV infection be confirmed?
By finding a positive screening test (usually a rapid test). The rapid test can be done in a primary-care clinic. A negative test may be repeated after 2 weeks if acute seroconversion illness is suspected. All patients must be informed and counselled, and must give consent before a rapid test is done. Documentation of verbal consent is adequate in most cases in people over the age of 12 years.
4. What is the window period?
The period between HIV infection and a screening test becoming positive. In the window period the HIV blood test may be falsely negative (the test is negative but the person is infected with HIV). The window period usually lasts up to 6 weeks. Some people with acute seroconversion illness may still be in the window period.
5. How does HIV cause disease?
By killing CD4 cells and, thereby, damaging the immune system. As a result the body is unable to protect itself from a wide range of viral, bacterial, fungal and parasitic infections.
6. What effect is HIV having on society in Africa?
The HIV epidemic is having a devastating effect on society. In 2018 it was estimated that about 7.7 million people in South Africa are living with HIV. Most are female.
Case study 3
A 25-year-old man is seen at a primary-care clinic with herpes zoster (shingles) which is very painful. He has also lost some weight and complains of recurrent mouth ulcers. On examination he has generalised lymphadenopathy and typical pruritic papular eruption. His HIV test was positive 4 years ago when he was screened at work. He is still able to continue working and refused ART.
1. How would you grade the clinical stage of HIV infection in this patient?
He should be graded as stage 2. Herpes zoster, recurrent aphthous mouth ulcers and skin rashes with mild weight loss are seen in stage 2 HIV infection. The rapid test confirms the clinical diagnosis. Patients in stage 2 can usually continue working.
2. What would the staging be if he only had lymphadenopathy and was generally well?
3. What is pruritic papular eruption?
Pruritic papular eruption (PPE or ‘itchy bump disease’) is common in patients with symptomatic HIV infection. It presents with scattered pigmented papules (bumps) which are very itchy. The rash is usually seen on the trunk and limbs. It is difficult to treat and responds poorly to topical steroids but usually resolves completely after a few months of ART.
4. What other skin rashes are common in patients with stage 2 HIV infection?
Seborrhoeic dermatitis, molluscum contagiosum, warts, scabies and psoriasis. Bacterial and fungal infections are also very common.
5. What are common causes of a painful mouth in patients with HIV infection?
A painful mouth is a common complaint in patients with HIV infection. Recurrent aphthous ulcers, oral candidiasis, herpes ulcers and infected gums are frequently seen. Kaposi’s sarcoma and oral hairy leucoplakia are usually not painful.
6. How long is the latent period?
This varies between people. However, many people with HIV infection but no treatment remain well (asymptomatic) for about 10 years (except for possible acute seroconversion illness) before developing clinical signs and symptoms of HIV infection.
Case study 4
A woman presents with a cough and night sweats for 6 weeks and a number of painless, purple patches on her skin. She has oral thrush and difficulty swallowing. Her husband died of AIDS the year before. On testing she is HIV positive.
1. What is the most likely cause of the cough and night sweats?
She almost certainly has pulmonary tuberculosis.
2. What condition causes multiple, painless purple patches in a patient with HIV infection?
Kaposi’s sarcoma. These patients may have multiple purple or brown skin patches or nodules. The mouth, lymph nodes, lungs and gut may also be involved.
3. Why is she having difficulty swallowing?
The finding of oral thrush (oral candidiasis) and difficulty swallowing suggests that she may have oesophageal candidiasis.
4. Does she have AIDS?
Yes. Both Kaposi’s sarcoma and oesophageal candidiasis are AIDS-defining conditions as they are very rare in people with a normal immune system (i.e. they are opportunistic infections). She would therefore be graded as having stage 4 HIV infection – i.e. AIDS.
5. Is pulmonary TB an AIDS-defining illness?
No. If she only had pulmonary TB as a complication of being HIV infected she would be graded as stage 3. Extrapulmonary TB would make her stage 4.
6. What malignancies are associated with AIDS?
Malignancies associated with AIDS are Kaposi’s sarcoma, non-Hodgkin’s lymphoma and cervical cancer.