HIVAIDS/AIDS and Opportunistic Infections

Objectives
To Do For this topic you will need to:
 * View the presentation called: AIDS illnesses.
 * Review the material on the course wiki which covers the following topics:
 * AIDS illnesses - affecting mouth and intestines, the skin; the lungs; brain or nerves;
 * Prevention of opportunistic infections.


 * Explore information about anti-HIV drugs in the Library of Resources above - look for the section on Medications.


 * View the presentation by Dr Geoff Clover on opportunistic infections and treatment (including drugs) of HIV/AIDS. There are also some notes which were made during the presentation about some of the main points. Dr Clover spoke online via the web conferencing facility, Elluminate, on Wednesday 17 June, 2009. Dr Geoff Clover is an infectious disease consultant specialising in HIV/AIDS.

AIDS illnesses


AIDS is the term for the illness affecting a person who has HIV infection and whose immune system is no longer working well enough to provide protection against severe unusual infections. An HIV infected person is said to have AIDS when he or she has suffered one or more of a long list of illnesses, for example Pneumocystis carinii pneumonia, Candida albicans oesophagitis, Toxoplasma gondii encephalitis, etc. There is more about the AIDS symptoms and illnesses on Wikipedia. After recovery from the illness the HIV infected person may feel even more healthy than before the illness was diagnosed and treated but he or she is still said to have AIDS. It is worth noting that in the United States a diagnosis of AIDS is made when people with HIV infection and a T helper lymphocyte count below 200 regardless of whether or not they have ever had any noticeable illness. Some patients resent the term AIDS and consider it an arbitrary definition which is inconsistent with their own perceptions of their health.

If people have not been tested or diagnosed in the early stages of HIV infection, the first signal of illness may be an opportunistic infection indicating AIDS. The T helper lymphocyte count at the time an HIV infected person suffers his or her first AIDS illness is usually below 200. However some patients will remain free of AIDS illnesses for months or years after the T helper lymphocyte count has fallen to extremely low levels (e.g below 10) while a few unlucky people develop AIDS illness when their count is still above 300. Most AIDS illnesses are very unusual in people who do not have an HIV infection (exceptions include Candida albicans and Herpes simplex), and only occur in people with organ transplants or cancer who are being treated with drugs that powerfully suppress the immune system.

Illnesses affecting the mouth and intestines



 * Candida albicans


 * Inflammation of the mouth due to Candida albicans occurs at some time in almost every HIV infected person. It causes a white coating (thrush) which is usually worst on the roof of the mouth and the inside of the cheeks. The mouth is sometimes sore and taste is altered. Severe cases can also affect the oesophagus (the tube which connects the mouth to the stomach) and cause pain when swallowing. Sometimes Candida albicans causes cracking of the lips at the corners of the mouth as well as thrush in the mouth. Because thrush has such a characteristic appearance it is not usually necessary to do any laboratory tests to confirm the diagnosis.


 * Infection due to Candida albicans can be treated with mouth washes, pastilles, gel or pills. All are about the same in treating mouth infection but only the pills are effective for oesophageal infection. Both mouth and oesophageal infection are usually cured within a few days of starting treatment. Because thrush recurs so frequently patients should have a supply of medicine available so that recurrences can be treated immediately.


 * Oral hairy leukoplakia (OHL) and gingivitis


 * Oral hairy leukoplakia is a thin white line on the edges of the tongue caused by heaping up of normal mucosal cells. It is not usually painful but it may affect taste. It often comes and goes without any obvious reason. Gingivitis, or inflammation of the gum margins, may cause severe mouth pain. It should be treated with mouth washes and antibiotics may be necessary.


 * Mouth ulcers


 * Large painful ulcers, often half to one centimeter across and almost as deep, can occur in the mouth and oesophagus. They are more common in patients treated with ddC (zalcitabine, Hivid). Topical steroid paste, a short course of steroid tablets or a long-term treatment with thalidomide are all helpful.


 * Diarrhoea


 * Diarrhoea is a common problem for HIV infected patients. It may occur occasionally or may be persistent. It is often associated with bloating, nausea and abdominal pain and may alternate with periods of normal bowel motions or constipation. A variety of infections may cause diarrhea but in many patients no cause can be found despite repeated tests. Some infections can be treated but often the only useful treatment is with drugs which make the bowel motion more firm. Special liquid food supplements may be helpful to reduce weight loss in patients with severe persistent diarrhea.

Illnesses affecting the skin

 * Kaposi’s sarcoma (KS) is a cancer of blood vessel cells which is caused by a newly discovered virus (Human Herpes Virus 8). It produces firm, non-tender, purple nodules in the skin, which usually do not ulcerate or bleed. Kaposi’s sarcoma may also occur in the mouth, in lymph glands and in other parts of the body. It is common for a few nodules to appear and then for no more nodules to develop for many months. This HIV-positive patient presented with an intraoral Kaposi’s sarcoma lesion with an overlying candidiasis infection. The patient also exhibited a CD4+ T-cell count <200, and a high viral load. Initially, the KS lesions are flattened and red, but as they age they become raised, and darker, tending to a purple coloration.


 * Kaposi’s sarcoma often does not require and treatment, but if the nodules are disfiguring they can easily and quickly be treated with radiotherapy. Occasionally if Kaposi’s sarcoma causes widespread disease it may be worth attempting to treat it with anticancer drugs or Interferon but the side-effects of these treatments may be worse than the disease itself.


 * Fungal skin infections are very common in patients with HIV infection and often begin years before any other HIV related illnesses. Most HIV infected patients will at some time have an area of dry, red, scaly skin which is usually about one centimeter in diameter and which gradually enlarges as similar patches appear nearby. These patches of tinea or ringworm usually do not cause any significant symptoms. The fungus responsible for the rash can usually be seen when flakes of skin from the rash are examined with a microscope. Small patches of tinea can be treated with ointment but when large areas of skin are affected it is often easier to treat the condition with pills. Treatment should be continued for a few weeks and often needs to be repeated when the rash reappears.


 * Seborrheoic dermatitis is a rash caused by the same fungus as that responsible for dandruff. It causes a greasy, red, scaly rash on the forehead, near the eye-brows and beside the nose. It is easily treated with anti-fungal creams.


 * Herpes simplex virus (HSV) causes a rash which usually affects a small area of skin about one to two centimeters in diameter. It usually heals completely after one to two weeks but often reappears in the same place weeks or months later. The most common location for the rash is near the anus, on the buttocks or thighs, or on the penis or vulva. The rash starts with an itchy red area followed by the development of tiny blisters filled with a clear fluid. The blisters burst to leave small painful ulcers which usually heal after a few days. Sometimes the ulcers may be large and may persist for weeks or even months.


 * The virus can be seen with an electron microscope in fluid and cells from the base of the blister or ulcer. It can also be grown in the laboratory. Antiviral tablets help to make the rash heal faster but ointments do not have any useful effect. Patients who have had an episode of herpes should keep some tablets available so that they can start treatment immediately if the rash recurs. Occasionally the Herpes simplex virus becomes resistant to the tablets and intravenous treatments may need to be used.


 * Varicella zoster virus (VZV) causes shingles, a rash which affects a narrow band of skin on one side of the body. The rash may affect any part of the body from the scalp to the toes. It always presents as a strip which either runs around the body from the middle of the back to the middle of the front, or else just down one arm or leg. There is often pain and increased sensitivity in the skin before the rash appears. The affected skin then becomes red with many small blisters which form scabs and ulcers and these finally heal after about 10 to 14 days.


 * The virus can be seen using an electron microscope but is difficult to grow. Treatment with antiviral tablets can reduce the duration of the rash and painkillers are also often necessary.

Illnesses affecting the lungs

 * Pneumocystis carinii pneumonia (PCP) was once a common illness and cause of death in HIV infected people. It can be prevented by regularly taking cotrimoxazole and is now less common. It causes breathlessness and a dry cough which gradually worsens over days to weeks. In about 80% of patients with PCP, Pneumocystis carinii can be seen when sputum or fluid washed out of the lungs is examined with a microscope. It is usually treated with Cotrimoxazole but this drug commonly causes allergic skin rashes and other drugs may have to be used. It frequently takes four to six days before treatment starts to make an improvement in how patients feel. Most patients with PCP can be cured but about 10 to 20% will die from the illness.


 * Patients who recover from PCP are very likely to have a recurrence of PCP within a year or two unless they take some medicine to prevent recurrences. People who have not had PCP but have a T helper lymphocyte (CD4) count below 200 are also very likely to suffer from PCP and also should regularly take preventative medicine such as Cotrimoxazole.


 * Tuberculosis is an uncommon illness in HIV infected people except for those people who live in third world countries or in the poorest parts of developed countries. However it has been a cause of great concern in some Western countries because it can be easily spread by cough droplets. Some strains of Mycobacterium tuberculosis are resistant to antibiotics and therefore difficult or impossible to treat. Tuberculosis usually affects the lungs or the lymph nodes causing fever, sweats, tiredness and weight-loss.


 * When TB involves the lungs it causes breathlessness and a cough with brown bloodstained sputum. When it affects the lymph nodes the patient develops painful swollen glands in the neck, armpits or groin. Mycobacterium tuberculosis can often be seen when sputum or a lymph node is examined with a microscope and may be grown in the laboratory. Treatment is always with a combination of drugs which need to be taken for several months.


 * Patients with tuberculosis affecting the lungs are usually cared for in a single room with special ventilation. This prevents air which has been contaminated with coughed-out bacteria from being breathed in by other patients. After about ten days treatment the number of bacteria in the sputum is usually so low that these strict isolation precautions can be stopped. People who have been in contact with a patient with tuberculosis will usually be offered tests to try to determine whether they have been infected. A chest X-ray may show signs of lung infection. Redness and swelling around an injection of killed bacteria injected into the skin of the forearm (the Mantoux test), may indicate that the person’s immune system is actively fighting Mycobacterium tuberculosis somewhere in the body. If either the chest X-ray or the Mantoux test indicate recent infection, the person will probably be advised to take some pills for several months to try to prevent tuberculosis from developing.


 * Pneumonia and bronchitis is an increased risk for patients with HIV infection and they are caused by ordinary sorts of bacteria which often affect elderly people and smokers. These illnesses cause cough, breathlessness, fever, brown sputum and sometimes chest pain and need to be treated with an antibiotic for one or two weeks.

Illnesses affecting the brain or nerves

 * Toxoplasmosis is caused by Toxoplasma gondii, a parasite excreted by cats. Approximately one third of all adults are infected in childhood and carry the infection for the rest of their lives. In HIV infected patients with a low T helper lymphocyte count, the infection may reactivate to produce abscesses in the brain. The position of these abscesses in the brain determines how the patient is affected, for example with weakness of one side of the body, or difficulty with speech or balance. The abscesses commonly also cause headaches, fever, nausea and vomiting.


 * A head CT scan or MRI scan can show the abscesses in the brain and treatment with antibiotics usually produces complete recovery within two weeks. Maintenance treatment with a reduced does of the same or similar antibiotic is necessary for the rest of the person’s life to prevent new abscesses developing. The antibiotics most commonly used to prevent Pneumocystis carinii pneumonia are also extremely effective at preventing toxoplasmosis, and therefore a patient who is taking PCP prophylaxis should not get toxoplasmosis.


 * Brain lymphoma may produce the same symptoms as toxoplasmosis and it can sometimes be difficult to distinguish between these two illnesses. The CT scan or MRI scan may be helpful in determining which disease is affecting the brain. Testing some of the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, for the presence of Epstein Barr virus can help to diagnose brain lymphoma. Radiotherapy can provide some short-term benefit but brain lymphoma is usually fatal within a few months.


 * Cryptococcal meningitis is caused by a fungus called Cryptococcus neoformans. Patients develop fever, headache, nausea and slowed thinking over days to weeks. Sometimes looking at bright light is painful and it may hurt the neck or back when the head is tilted forwards. The disease is readily diagnosed by finding the fungus in the CSF or in the blood. Treatment with antifungal drugs, which may need to be given intravenously at first, will usually cure the disease within a few weeks. Maintenance treatment with capsules needs to be continued lifelong to prevent recurrences.


 * Cytomegalovirus (CMS) retinitis is a disease which may affect the back of one or both eyes and causes patches of blurred or lost vision which may gradually enlarge to produce complete blindness unless treated. The disease can usually be diagnosed by looking at the back of the eye, and detecting cytomegalovirus in the blood helps to confirm the diagnosis. Cytomegalovirus retinitis can be usually brought under control with intravenous or oral treatment, but eyesight often remains impaired to some degree. Treatment must be continued permanently to prevent the disease reactivating.


 * The image depicts a funduscopic examination of a 16-year-old girl with HIV infection and cytomegalovirus retinitis. There are extensive areas of hemorrhage, with white retinal exudates. Children with cytomegalovirus retinitis usually present with painless visual impairment (courtesy of Dr David Coats, Houston, Texas).


 * HIV encephalopathy, sometimes called AIDS dementia, causes a generalized or irreversible deterioration in brain functioning. Patients gradually lose concentration, memory and motivation. Sometimes episodes of manic, enthusiastic, and often inappropriate, behavior may occur during the gradual intellectual decline. It is thought that HIV encephalopathy is due to HIV itself or to the immune response to the virus, and that long-term treatment with anti-HIV drugs may help to prevent it. While complex psychological testing can find subtle evidence of mild HIV encephalopathy in many HIV infected persons, the disease only causes obvious problems for a small minority of patients.


 * Peripheral neuropathy, which is due to HIV damaging the longest nerves in the body, causes pain and unusual sensitivity in the feet and sometimes in the hands. Both sides of the body are equally affected, with the changes in feeling starting in the tips of the toes and the soles of the feet. Strength and coordination are not affected. Sometimes the painful sensations are sufficiently disturbing to need treatment with painkillers.


 * Mycobacterium avium complex (MAC) is a bacterium similar to the one which causes tuberculosis. Mycobacterium avium is widespread in water and soil and may infect the body after being breathed into the lungs or swallowed with water or food. In HIV infected people with very low T helper lymphocyte counts, it then multiplies in the liver, spleen, lymph nodes and bone marrow, and extremely large numbers of bacteria are released into the blood. Patients suffer very high fevers, drenching sweats and severe shivering episodes, and lose their appetite and energy. Usually there are not any symptoms to suggest that one part of the body is more affected than other parts.


 * Disease due to Mycobacterium avium can be confirmed by growing the organism from a sample of the patient’s blood, but as it is a slow growing bacterium the test usually takes two to three weeks. The symptoms commonly resolve within two weeks of starting treatment with a combination of antibacterial drugs but treatment needs to be continued permanently to prevent recurrences.

Prevention of opportunistic infections
Patients with HIV infection may be encouraged to take medicines. Anti-retroviral drugs are given to prevent HIV infecting more cells and thus delay or reverse the weakening of the immune system. Many of the anti retro-viral medications are expensive and have severe side-effects. Many antibiotics and other similar drugs are used to treat opportunistic infections and help patients recover from AIDS illnesses. Preventive (or prophylactic) drugs, including antibiotics, are used to prevent or delay the onset of opportunistic infections.

Pneumocystis carinii pneumonia (PCP) is so common in people with a T helper lymphocyte count below 200 and is such a severe illness that all HIV infected patients with a T helper lymphocyte count below 200 should consistently use some prophylaxis. Cotrimoxazole (Septrin, Bactrim), dapsone or pentamidine all reduce the chance of an HIV infected person developing PCP. Cotrimoxazole is the most effective drug but some patients get a severe rash and cannot continue taking the drug. Cytomegalovirus retinitis is relatively common in people with a T helper lymphocyte count below 50. Mycobacterium avium complex (MAC) is a relatively common cause of disease in people with a T helper lymphocyte count below 50. Prophylatics can reduce the chance of MAC disease. Patients who have been infected with Mycobacterium tuberculosis have a very high chance of developing tuberculosis even when their T helper lymphocyte count is still quit high. An injection of dead tuberculosis protein into the skin on the forearm (the Mantoux test) can determine which patients have been infected with Mycobacterium tuberculosis and therefore are at risk of developing disease. A previous BCG vaccination, intended to prevent tuberculosis, can make the Mantoux test result difficult to interpret. Prophylaxis with isoniazid for six months will reduce the chance of developing tuberculosis. Most experts recommend that HIV infected patients with a high chance of having been infected with Mycobacterium tuberculosis should have the Mantoux test and if this is positive, be treated with isoniazid.

Patients who have suffered an episode of Herpes simplex ulcers are very likely to have recurrent episodes in the future. Some experts recommend regularly daily prophylaxis with acyclovir or another similar drug. Others suggest taking treatment at the first symptoms of a recurrence.

Almost all HIV infected patients will have a episode of Candida albicans pharyngitis at some time. While regular prophylaxis with an antifungal drug can prevent recurrences many experts recommend treatment of recurrences rather than continuous prophylaxis.

The advice given to an HIV infected person about which drugs to take to prevent opportunistic infections may differ from one doctor to another depending on how common the opportunistic infection is, how effective and safe the prophylaxis is, and the expense of the prophylactic medicine.