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HIV-associated infections (or opportunistic infections) are infections which are common in patients with HIV infection. They ‘take the opportunity’ of infecting and causing illness in patients with a weakened immune system.
HIV-associated infections are common in patients with a weakened immune system.
The following infections are uncommon in HIV-negative people, but common in HIV-positive people:
The following infections are rare in HIV-negative people and are AIDS-defining. This means that people who have these infections usually have HIV infection.
No, as many of the milder HIV-associated infections such as pulmonary TB or shingles may also be found in HIV-negative patients and patients with stage 1 to 3 HIV infections (i.e. not AIDS). These infections, however, should always alert one to the fact that the patient may have HIV infection. HIV-associated infections are therefore an important indicator for HIV counselling and screening.
Clinical conditions that are so rare in people with a healthy immune system that they usually indicate that the person has AIDS (stage 4 HIV infection). AIDS-defining illnesses include:
Both infections and malignancies can be AIDS-defining illnesses.
The lower the CD4 count, the higher the risk of getting an HIV-associated infection.
The best way of preventing most severe HIV-associated infections and TB is to start antiretroviral treatment in HIV patients when their CD4 count reaches 500 cells/µl. The risk of HIV-associated infections can also be reduced by:
Oral candidiasis (also called thrush or moniliasis) occurs mostly in HIV patients with a CD4 count below 200 cells/µl. It is a Stage 3 disease and may indicate advanced immunodeficiency. The patient complains of a painful mouth and white patches are seen on the tongue, palate and inside the cheeks. White patches may also be seen in the pharynx (oropharyngeal candidiasis). HIV-infected women often have severe or repeated vulvovaginal candidiasis.
Oral candidiasis in adults is often an early sign that the patient has HIV infection.
Candidiasis of the mouth and pharynx can be treated with topical nystatin drops 1 ml every six hours. A patient may also suck amphotericin B lozenges and patients who do not respond may be treated with fluconazole 100 mg daily for seven days. Recurrences are common in patients who are not on ART.
Most HIV patients are at an increased risk of serious or repeated bacterial infections such as:
A wide range of bacteria may cause meningitis or pneumonia such as Pneumococcus, Haemophilus and Staphylococcus. These infections should be treated as for patients who are not HIV positive.
Prophylaxis with co-trimoxazole reduces the risk of many bacterial infections.
Common bacterial infections are often serious or recurrent in HIV patients.
A number of organisms that do not cause problems in healthy people may cause chronic diarrhoea in HIV-infected patients. Examples are non-typhoid Salmonella, Cryptosporidium and Isospora. Patients with severe or chronic diarrhoea should be referred to hospital if dehydrated.
Shingles (Herpes zoster) is a very painful vesicular rash which usually only affects one part of the body. It is commonly seen in older people and is uncommon in young healthy adults. It is caused by reactivation of the chickenpox virus (Varicella zoster) which has been silent in nerve cells since a childhood infection. Shingles is infectious and can cause chickenpox in children. Pain typically occurs for a few days before the rash appears.
Shingles is common in young adults with HIV infection as their damaged immune system no longer keeps the virus under control. Patients with shingles should be treated early with high doses of oral acyclovir (800 mg 4-hourly for five days). The eye may become involved, which can cause blindness. Patients with face or eye involvement should be urgently referred to hospital for treatment.
Shingles in a young adult suggests HIV infection.
A painful, recurrent rash with many small vesicles in the genital or anal area is usually due to a Herpes simplex infection. This sexually transmitted disease is often severe and recurrent in patients with HIV infection due to their damaged immune systems. The mouth and lips may also be involved. Patients with severe infection should be treated with oral acyclovir (400 mg 8-hourly for five days).
Recurrent, severe herpes is common in HIV patients.
In contrast, oral hairy leucoplakia is not painful and does not require any treatment.
Oesophageal candidiasis is very common in patients with a CD4 count below 100 cells/µl. Patients present with pain and difficulty on swallowing. Patients with oesophageal candidiasis usually have oral candidiasis as well, which helps make the diagnosis. Oesophageal candidiasis may result in dehydration due to poor fluid intake.
Oesophageal candidiasis presents with painful swallowing and almost always indicates advanced HIV infection.
Oesophageal candidiasis is treated with oral fluconazole (200 mg daily for 14 days). Local treatment with topical drugs is not adequate. Patients with oesophageal candidiasis must be referred to hospital if they need intravenous rehydration. It is useful to give patients a glass of water to drink so that you can assess how easily they are able to swallow.
Pneumocystis pneumonia is a severe lung infection caused by a fungus called Pneumocystis. HIV patients, especially children, are particularly likely to develop pneumocystis pneumonia if their CD4 count is below 100 cells/µl.
The patient presents with:
Early in the infection the chest X-ray may appear normal. Later the appearance is that of ‘ground glass’, often involving both lungs.
Oral co-trimoxazole, four tablets every six hours in patients of 60 kg or more and three tablets every six hours in patients under 60 kg, is the treatment of choice. Severe cases also require steroids. Patients with severe pneumonia need to be hospitalised, and will need oxygen.
Yes. Prophylactic oral co-trimoxazole, two tablets daily should be given to HIV-infected patients with a CD4 count below 200 cells/µl or stage 2, 3 or 4 disease. Prophylaxis can be stopped when the CD4 count is above 200 cells/µl after starting treatment.
Prophylactic co-trimoxazole can lower the risk of the following HIV-associated infections:
Yes. Especially in patients who are receiving antiretroviral treatment. The commonest side effect is a rash. This can be severe and even life threatening. The rash can occur for the first time even if the patient has been on co-trimoxazole treatment for many months or years.
This is a serious infection of the meninges caused by a fungus called Cryptococcus neoformans. Cryptococcal meningitis is rare in healthy people and is not infectious to others. It is usually seen in patients with advanced HIV infection and a CD4 count below 100 cell/µl.
Cryptococcus is an important cause of meningitis in patients with advanced HIV infection.
It presents with the clinical signs of meningitis, i.e. fever, headache, nausea and vomiting, neck stiffness, confusion and drowsiness.
The diagnosis is confirmed by examining the cerebrospinal fluid (CSF) obtained by lumbar puncture. The diagnostic tests on the CSF are:
All patients with a clinical suspicion of meningitis must be urgently referred to hospital. Amphotericin B is given intravenously for two weeks followed by high oral doses of fluconazole for a further eight weeks.
Yes. Patients with CD4 counts below 100 cells/µl should have blood taken for a cryptococcal latex agglutination test (CLAT) and if positive and asymptomatic, should receive primary prophylaxis with fluconazole. The dose for primary prophylaxis is 800mg fluconazole by mouth daily for 2 weeks, then 400mg daily by mouth for 8 weeks, then 200mg per day until the CD4 count is above 200cells/µl for at least 6 months.
Patients who have been treated and have recovered from cryptococcal meningitis should be placed on secondary fluconazole prophylaxis to reduce the risk of a repeat infection. The dose of daily oral fluconazole for secondary prophylaxis is 200 mg daily. Prophylaxis can be stopped when the CD4 count rises above 200 cells/µl.
Toxoplasma gondii is a single-cell organism (parasite) that can cause serious illness with brain infection (encephalitis) in patients with advanced HIV infection and a CD4 count below 100 cells/µl. Toxoplasmosis is not infectious to others. Patients with cerebral toxoplasmosis present with fits, abnormal behaviour and/or drowsiness. The diagnosis is confirmed on CT scan. Patients with suspected cerebral toxoplasmosis must be urgently referred to hospital for investigation and treatment with a prolonged course of co-trimoxazole.
Cerebral toxoplasmosis is a serious complication of AIDS.
This virus commonly causes mild illness in healthy children and adults. Most people are infected as children. In HIV-infected patients with a very low CD4 count, CMV may cause retinitis (infection of the eye), encephalitis (brain infection), hepatitis, pneumonitis and bowel infection. This may be a primary infection or recurrence of a childhood infection.
CMV retinitis presents with sudden impaired vision and is the commonest cause of blindness in HIV patients with low CD4 counts. Suspected cases must be urgently referred to hospital for diagnosis and treatment with ganciclovir. Visual impairment caused by CMV may be permanent.
CMV retinitis may cause blindness in HIV patients.
Tuberculosis co-infection occurs when the patient has tuberculosis and HIV infection at the same time.
Tuberculosis (TB) is a chronic infectious disease which is caused by TB bacteria. Tuberculosis disease usually affects the lungs (pulmonary tuberculosis), but may involve other organs (extrapulmonary tuberculosis).
TB bacteria are usually spread when a person with untreated pulmonary tuberculosis talks, coughs, spits, laughs, shouts, sings or sneezes. This sends a spray of very small droplets into the air. These small drops contain live TB bacteria (TB bacilli) from the person’s lungs. They float in the air for up to one hour and can be breathed in by other people. This may result in TB infection of the lung. Patients with many TB bacteria in their sputum (‘open TB’) are very infectious to others.
TB bacteria are spread by people with untreated pulmonary tuberculosis.
No. Most people infected with TB bacteria do not develop tuberculosis because their healthy immune system is able to control the infection and stop the TB bacteria from multiplying and spreading. However, the TB bacteria are often not all killed but only kept under control. The normal immune response in people without HIV infection prevents the TB infection from progressing to tuberculosis (TB disease).
Fortunately most HIV-negative people infected with TB bacteria do not develop tuberculosis.
This will depend on the ability of the person’s immune system to control the spread of the TB bacteria. If the immune system is strong the TB infection will be well controlled and not spread to other parts of the lung or to other organs (primary infection only, without progressing to tuberculosis). However, if the immune system is weak, the TB infection may rapidly spread within the lung or to other organs (tuberculosis or TB disease). Some patients are able to control the primary infection for months or many years (latent phase) but the infection may then spread to cause tuberculosis if the immune system becomes weakened (reactivation).
Infection with TB bacteria is very common, and it is estimated that almost 50% of all South Africans are infected, especially during childhood. However, only about 10% of healthy, HIV-negative people with TB infection develop tuberculosis disease during their lifetime. Therefore, TB infection is far more common than tuberculosis in the general population.
TB infection is very common in South Africa.
Yes. Tuberculosis is very common in people with HIV infection, and is often the first indication of illness in a person who is HIV positive. All patients with HIV infection are at an increased risk of developing tuberculosis because of their suppressed immune system. In HIV-positive people, new primary TB infection progresses to tuberculosis in 30% of cases, while an additional 10% per year will develop tuberculosis disease due to reactivation of an old latent TB infection. This contrasts with HIV-negative people who only have a small risk of developing tuberculosis in their lifetime. HIV has therefore changed the natural history of tuberculosis, making it the most common HIV-associated infection in South Africa.
Tuberculosis is very common in HIV-positive people and is the most common HIV-associated infection in South Africa.
In South Africa over 50% of adults with tuberculosis are also HIV positive. It is therefore essential to screen for HIV in all patients presenting with tuberculosis.
All patients with tuberculosis must be screened for HIV infection.
HIV-positive patients have damaged immune systems which are not able to control the TB infection. Tuberculosis in HIV-positive people may be due to either:
HIV infection probably does not increase the risk of TB infection but greatly increases the risk of old or new TB infections progressing rapidly to tuberculosis.
The course of tuberculosis is often very rapid in patients with HIV infection. Both new and old TB infections spread quickly. Therefore, patients with both HIV infection and tuberculosis may need hospitalisation.
The course of tuberculosis is very rapid in patients with HIV infection.
Tuberculosis is the most common cause of death in adults with HIV infection in South Africa.
Tuberculosis is the commonest cause of death in adults with HIV infection in South Africa.
Patients with untreated HIV infection become worse much more rapidly if they also have TB co-infection, which further damages the immune system.
Therefore, HIV infection speeds up the progress of tuberculosis while tuberculosis speeds up the progress of HIV infection. This is the great danger of HIV/TB co-infection.
The progress of HIV infection is made worse with TB co-infection.
Tuberculosis may affect most organs of the body, such as the lymph nodes, bowel, meninges, brain, kidneys and spine, especially in people with HIV infection. This is called extrapulmonary tuberculosis. The commonest form of extrapulmonary tuberculosis in HIV-positive people is enlarged lymph nodes (tuberculous lymphadenopathy). Tuberculous meningitis and disseminated tuberculosis are also common in HIV-infected patients. Disseminated tuberculosis presents with two or more organs involved.
The risk of extrapulmonary tuberculosis increases when the CD4 count is low. Therefore, extrapulmonary tuberculosis is more common in people with advanced HIV disease.
Patients with pulmonary TB may present with any of the following:
A careful history is the best way to screen for tuberculosis. Any two of the above symptoms or signs strongly suggests tuberculosis. Always suspect tuberculosis in any HIV-positive person who has a cough lasting more than two weeks. Advanced HIV infection can also result in fever, night sweats, weight loss, tiredness and weakness.
Pulmonary tuberculosis usually presents with chronic cough, fever, severe night sweats and weight loss.
Two sputum samples should be sent for testing for acid-fast bacilli (i.e. TB bacteria). If available, a GeneXpert test should be done. GeneXpert is a rapid and sensitive method of detecting TB bacilli in sputum. It can also determine if the TB bacilli are resistant to rifampicin. If the GeneXpert or smear result is positive, the patient should be started on TB treatment.
Smear-positive patients have pulmonary tuberculosis and are infectious.
Sometimes the clinical diagnosis of tuberculosis is difficult to confirm.
Any patient with pulmonary tuberculosis may be infectious to the general public. As the number of HIV patients with tuberculosis increases, the risk of tuberculosis in HIV-negative people will also increase as they are being exposed to more TB bacteria. As a result of the HIV epidemic, tuberculosis has become a common disease in South Africa. It is therefore in the public’s best interest to prevent and manage tuberculosis well.
The HIV epidemic is increasing the risk of tuberculosis to the general public.
Directly observed treatment (DOT) is a course of TB treatment where taking the medication is observed each day by a supporter. The supporter is a responsible friend or family member or a healthcare worker who makes sure that each dose of TB treatment is correctly taken.
HIV-infected patients at high risk of tuberculosis can be protected by isoniazid (INH) at a dose of 300 mg daily. Prophylaxis prevents the reactivation of an old TB infection as well as the spread of new TB infections.
It is suggested that TB prophylaxis should be given to HIV-positive patients who have a positive Mantoux skin test result of 5 mm or more. A positive Mantoux skin test indicates that the person has previously had TB infection. INH prophylaxis should be given for at least 36 months. It is very important to exclude active tuberculosis before starting INH prophylaxis as monotherapy with INH may lead to TB drug resistance.
TB prophylaxis is important in HIV-infected people at high risk of tuberculosis.
Yes. However, the TB treatment should be started before beginning antiretroviral treatment because:
Therefore treatment of HIV and tuberculosis at the same time has many problems. However, if antiretroviral treatment is delayed too long, the patient may become seriously ill or die.
Tuberculosis treatment should be started before starting antiretroviral treatment.
An intensive phase of treatment for two months is followed by a continuation phase of four months. Therefore, treatment for tuberculosis usually lasts six months.
Usually rifampicin, isoniazid (INH), pyrazinamide and ethambutol are given in a combination tablet for the intensive phase of treatment. Daily dosage with combination tablets is given according to body weight:
For the continuation phase, a combination tablet of rifampicin and INH only is used:
Tuberculosis in patients with HIV infection usually responds well to treatment.
The commonly used combination tablet for the intensive phase contains rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg and ethambutol 275 mg, while the combination tablet for the continuation phase contains rifampicin 150 mg and isoniazid 75 mg. Double-strength tablets are available for patients weighing 55 kg or more
Tuberculosis is treated with a multiple drug regimen using combination tablets.
As with antiretroviral treatment, it is extremely important that TB treatment is given correctly every day for the full course. Poor adherence is the main reason for treatment failure and an important cause of drug-resistant tuberculosis.
The risk of tuberculosis is greatly reduced in the short term in patients on antiretroviral treatment (in the first three years) as their CD4 counts are increasing. However, as patients on antiretroviral treatment now live longer, the lifetime risk of TB is still high. As a result, the incidence of tuberculosis in the community may not fall with the roll-out of antiretroviral treatment.
Yes. Tuberculosis should be excluded by taking a careful history before starting antiretroviral treatment. Any HIV patient with a chronic cough should be fully investigated for tuberculosis.
The antiretroviral treatment must be continued and TB treatment started. There is no need to delay starting the TB treatment.
In patients who are already on antiretroviral treatment when tuberculosis is diagnosed, some of the drugs being used in antiretroviral treatment may have to be changed:
As there are complex interactions between the drugs used to treat TB and the drugs used for antiretroviral treatment, the management of these patients may need to be reviewed by a doctor experienced in managing patients with TB/HIV co-infection.
Drugs used in TB therapy and antiretroviral treatment may interact with each other.
Nausea, rash, hepatitis and peripheral neuropathy may be caused by both the drugs used to treat tuberculosis and those to treat HIV. As a result these side effects (adverse effects) are commoner and may be more serious if the two drug regimens are used together. This may result in a change in the choice of antiretroviral drugs.
Drug side effects are more frequent and may be more severe if anti-tuberculous and antiretroviral treatments are given together.
Adherence may be poor when so many tablets need to be taken together. There may also be confusion between the many different types of tablets. Patients should be told they will have to take a large number of tablets and be counselled about these possible problems. A clearly written plan for both TB and antiretroviral treatment is helpful.
Tuberculosis resistant to many of the TB drugs is a growing problem in both HIV-positive and negative people. A combination of HIV infection and drug-resistant tuberculosis is often fatal. Therefore, good adherence is essential in the treatment of both tuberculosis and HIV to prevent drug resistance.
Multi-drug-resistant (MDR) TB is resistant to both INH and rifampicin. This is becoming a worry in South Africa.
There are important differences in the way that treatment is managed:
Previously HIV patients with tuberculosis co-infection were referred to a local TB clinic for treatment of their tuberculosis. This is unsatisfactory and HIV and TB infections should preferably be managed at a single clinic.
Patients with TB/HIV co-infection should be managed at a single clinic.
There are many advantages to the combined management of tuberculosis and HIV infection.
If all these steps are taken treatment adherence should be excellent and most patients should complete their full course of treatment. This will improve survival and reduce the risk of drug resistance.
A 20-year-old man presents with a very painful mouth for the past few days. On examination he has white patches on his tongue and palate. When questioned, he admits to difficulty swallowing.
Oral candidiasis. He probably also has oesophageal candidiasis as he has difficulty swallowing.
HIV infection with suppression of his immune function. Oral candidiasis is uncommon in healthy adults with a normal immune system.
Topical nystatin drops 1 ml every six hours. He could also suck amphotericin B lozenges or nystatin vaginal pessaries. Prescribe oral fluconazole or refer if the candidiasis is not cleared after five days of treatment.
Oral fluconazole. Make sure the patient is not dehydrated. If so, intravenous fluid may be needed. Dehydrated patients should be referred to hospital.
Aphthous ulcers, herpes ulcers and gingivitis.
Yes. An HIV-associated infection occurs far more commonly in HIV-positive people than people who are HIV negative. These infections are more common because HIV damages the immune system by reducing the CD4 count. Oral candidiasis indicates stage 3 disease.
A young woman complains of weight loss and chronic diarrhoea. For the past few days she has had severe pain on one side of her chest. She has noticed a rash with small vesicles (blisters) in the same area as the pain.
Herpes Zoster (Shingles). This typically presents as localised pain followed by a vesicular rash.
No, but both rashes are due to the Varicella zoster virus. For many years the virus remains in nerve cells following chickenpox as a child. When the immune system is weakened, the virus is reactivated, causing shingles. Shingles is infectious and can cause chickenpox in others.
It suggests that the person has HIV infection. Shingles is uncommon in healthy HIV-negative young people and is usually seen in an older person.
Early treatment with oral acyclovir. If the pain or rash involves the face or eye, the patient must be referred urgently to hospital.
This is almost certainly caused by an infection associated with HIV. A number of organisms cause chronic diarrhoea in HIV patients, such as non-typhoid Salmonella, Cryptosporidium and Isospora. She should be treated symptomatically and a stool sample should be sent for microscopy and culture. If the diarrhoea does not resolve despite treatment and ART, she should be referred to hospital for further diagnosis and treatment.
Prophylaxis with co-trimoxazole will help prevent diarrhoea due to bacterial infections as well as infections with Isospora.
A known HIV patient develops a dry cough and fever. After a few days he feels worse and becomes short of breath.
Pneumonia. Cough, fever and shortness of breath suggest a lung infection.
Bacterial pneumonia, pneumocystis pneumonia or tuberculosis. The most likely cause is pneumocystis pneumonia.
A chest X-ray will be helpful in most cases. Exclude tuberculosis and bacterial pneumonia. Where laboratory support and saline nebulization are available, request an examination for Pneumocystis in a sputum specimen.
Oral co-trimoxazole, four tablets every six hours in patients weighing 60 kg or more and three tablets every six hours in patients under 60 kg. Patients who are severely ill or cyanosed need oxygen and admission to hospital. Severe cases may need steroids.
These are conditions which are very rare in people who do not have AIDS (stage 4 HIV infection). Pneumocystis is an AIDS-defining illness, therefore anyone presenting with pneumocystis pneumonia almost certainly has AIDS. Certain malignancies such as Kaposi’s sarcoma and non-lymphoid lymphoma are also AIDS-defining illnesses.
Oesophageal candidiasis, cryptococcal meningitis, cerebral toxoplasmosis and CMV retinitis all indicate stage 4 HIV infection.
An HIV-positive patient presents with a chronic cough, night sweats and fever. A chest X-ray suggests pulmonary tuberculosis.
Very common. It is the commonest HIV-associated infection in adults in South Africa.
Yes, it is the commonest cause of death in adults with HIV in South Africa.
Controlling tuberculosis in the general population and the routine use of BCG immunisation in infants. TB prophylaxis (primary prevention) with isoniazid in HIV patients with a positive Mantoux skin test is effective in reducing the incidence of tuberculosis in these high-risk patients.
With a course of multi-drug therapy. Usually rifampicin, isoniazid, pyrazinamide and ethambutol are used together. HIV-positive patients with tuberculosis usually respond well to TB treatment.
If possible, TB treatment should be started first before starting antiretroviral treatment. Therefore all patients should be screened for tuberculosis before antiretroviral treatment is started. If the patient is already on antiretroviral treatment when the diagnosis of tuberculosis is made, the anti-tuberculosis treatment should be added to the antiretroviral treatment without delay.
Drugs used to treat tuberculosis and HIV often interact with each other. The risk of side effects is increased and adherence is often poor due to the large number of tablets that have to be taken each day.