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Adult HIV: HIV Infection

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Adult HIV was developed by doctors and nurses with wide experience in the care of adults with HIV, under the auspices of the Desmond Tutu HIV Foundation at the University of Cape Town. It covers: …

Adult HIV was developed by doctors and nurses with wide experience in the care of adults with HIV, under the auspices of the Desmond Tutu HIV Foundation at the University of Cape Town. It covers: introduction to HIV infection, management of HIV-infected adults at primary-care clinics, preparing patients for antiretroviral (ARV) treatment, ARV drugs, starting and maintaining patients on ARV treatment, opportunistic infections

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  • 1. 1 HIV infectionBefore you begin this unit, please take the Viruses are extremely small, very simplecorresponding test at the end of the book to organisms which can only exist and multiply byassess your knowledge of the subject matter. You invading and taking control of a plant or animalshould redo the test after you’ve worked through cell (the host cell). Viruses are responsiblethe unit, to evaluate what you have learned. for many diseases such as influenza and the common cold. Unlike bacteria they are not killed by antibiotics. Viruses may be divided Objectives into many different groups. HIV belongs to a group of viruses known as retroviruses. When you have completed this unit you People infected with HIV are said to be HIV should be able to: positive. • Define HIV infection and AIDS. • Explain how HIV is transmitted between people. HIV is the human immunodeficiency virus. • Appreciate why HIV infection is having a devastating effect on society. NOTE HIV was first identified in Paris in 1983. • Confirm the clinical diagnosis of HIV HIV is a new human virus which probably first infection. appeared in the 1950s when it was transmitted • Describe acute seroconversion illness. to humans from chimpanzees in central Africa. • Explain the asymptomatic and symptomatic phases of HIV infection. 1-2 What are retroviruses? • Describe the 4 clinical stages of HIV They are a group of viruses which are unique infection. in nature as they have a special enzyme • Recognise the clinical signs of HIV called reverse transcriptase. This enzyme infection. enables HIV to introduce its own genes into the nucleus of the host cell. The host cell is then instructed to produce millions of newINTRODUCTION TO copies of the virus. These are released into theHIV INFECTION bloodstream and can then infect other cells. Retroviruses usually cause long periods of silent infection before signs of disease appear.1-1 What is HIV? NOTE Retroviruses contain an RNA genetic code.HIV, the human immunodeficiency virus, is a The enzyme reverse transcriptase allows HIV tovirus which infects people for life. make double-strand DNA copies of its single- strand RNA. The DNA copy is then inserted
  • 2. 14 ADULT HIV into the DNA of the nucleus in the host cell. cells, HIV weakens the immune system which Only retroviruses have this ability to make a is then no longer able to prevent infection by DNA copy of their RNA code. Retroviruses are many viruses, bacteria, fungi and parasites. common and some cause cancers in animals. HIV infection damages the immune system. HIV is a retrovirus. NOTEAbout 10 billion copies of HIV are1-3 What disease is caused by HIV? produced each day in infected people.HIV causes a serious chronic illness calledAIDS (Acquired Immunodeficiency 1-6 Are there different types of HIV?Syndrome). Without treatment with Two types of HIV are recognised, HIV1 andantiretroviral drugs, AIDS is a fatal condition. HIV2. Most HIV infection in southern Africa is caused by HIV1, which has many subtypes (clades). The important subtype in Africa is HIV causes AIDS. subtype C. Subtype B is the most common subtype in the developed world.1-4 What is AIDS?AIDS is a clinical syndrome which presents inpeople with advanced HIV infection (severe THE SPREAD OF HIVHIV disease). It can present in many differentways. The symptoms and signs of AIDS areusually due to secondary infections with a 1-7 Is HIV infectious?number of different organisms not normally Yes. HIV infection can be spread from oneseen in HIV-negative people. People with person to another.AIDS are always HIV positive.The terms ‘symptomatic HIV’ or ‘HIV disease’ 1-8 How is HIV transmitted fromare also used for patients who are clinically ill one person to another?because of HIV. These patients may not yet be The virus may be transmitted from one personill enough to be labelled as having AIDS. to another by: 1. Unprotected sexual contact (horizontal AIDS is a severe illness which presents in people transmission). Body fluids such as vaginal who have advanced HIV infection. and cervical secretions, semen and blood contain large amounts of HIV. HIV is not1-5 How does HIV cause disease? present in urine or stool, while very little is present in saliva.HIV invades and destroys the immune system 2. Crossing from a mother to her fetus orby damaging the CD4 lymphocytes.As the newborn infant (vertical transmission).CD4 cells play a very important role in the 3. Using syringes, needles or blades which arefunctioning of the immune system, HIV soiled with HIV-infected blood. They mayinfection of CD4 cells damages the immune be shared by intravenous drug abusers orsystem, leading to immune deficiency. not correctly cleaned and then reused byTherefore, HIV destroys more and more CD4 health workers.cells, and the body’s immune system becomes 4. Accidental needle-stick injuries.weaker and weaker. 5. A blood transfusion with HIV-The normal immune system protects the body infected blood or other HIV-infectedagainst infection. Therefore, by killing CD4 blood products such as factor VIII in haemophiliacs. This is very rare in South
  • 3. HIV INFECTION 15 Africa, where all blood products are 1-11 How can the sexual spread of HIV screened for HIV. in the general public be reduced?There is no evidence that HIV can be spread Through the behavioural change of ‘ABC’:by mosquitoes, lice or bed bugs. In Africa, 1. ‘A’ – Abstinence (no sex) and delay inHIV is most commonly spread by heterosexual sexual debut (first-time sex).intercourse. 2. ‘B’ – Be faithful to one partner (reduce the number of sexual partners).1-9 What forms of sexual 3. ‘C’ – Use a condom (especially when notcontact may transmit HIV? being faithful to one partner).HIV is almost always transmitted by The reduction in number of sexual partnerspenetrative sexual intercourse (heterosexual or seems to have resulted in the declining HIVhomosexual). However, all forms of oral sexual prevalence in countries such as Uganda.contact (mouth to vagina or mouth to penis) However, all three behavioural changes arecan also result in infection, although the risk important.is less. Deep kissing rarely transmits HIV,unless mouth ulcers are present. HIV cannot NOTEThe diaphragm may alsopenetrate intact skin but may infect through reduce the risk of HIV infection.open sores, cuts and abrasions, or mucousmembranes. Infection is more common in 1-12 Can you have HIVuncircumcised men than circumcised men. infection and not be ill?The highest risk of sexual transmissionfor both men and women is during anal Yes. A person is usually infected with HIVintercourse. The thin, friable rectal mucosa is for years before becoming ill. Therefore, mosteasily damaged during anal intercourse, which people infected with HIV are clinically wellincreases the risk of infection. The presence of (asymptomatic) for many years.any other sexually transmitted infection willalso increase the risk of HIV infection. 1-13 Can an HIV-infected person who is well transmit the virus? In South Africa, HIV is usually spread by sexual Yes. HIV is frequently transmitted by people intercourse. who appear to be clinically well but are infected with HIV. This is the great danger of HIV infection as most infected people do notSexual abuse and rape may also result in HIV know that they have been infected. They areinfection. also unaware that they may transmit HIV to another person.1-10 Can you become infected withHIV during normal social contact? 1-14 How common is HIV infection?No. Family and friends of an HIV-infected Over 40 million people worldwide have HIVperson do not become infected except by infection. It is estimated that 6 million Southsexual contact. HIV is not transmitted by Africans are infected with HIV. In 2008, 29.3%close social contact such as touching, holding of all pregnant women in South Africa werehands, hugging and social kissing. HIV is also infected with HIV. The province of KwaZulu–not spread by coughing, sneezing, swimming Natal had the highest prevalence of 38.7%.pools, toilet seats, sharing cooking, drinking In some antenatal clinics, more than 50% ofand eating utensils or by changing a nappy. pregnant women were HIV positive.However, any bleeding, such as nose bleeds,may spread HIV.
  • 4. 16 ADULT HIV1-15 How often does HIV prophylactically. The risk of mother-to-childinfection cause death? transmission can be reduced to below 5% by:It is estimated that 600 people die of HIV 1. Giving the mother AZT from 14 weeks untilinfection each day in South Africa. Many delivery, AZT 3-hourly plus a single dose ofof these deaths could be prevented with the nevirapine during labour and a single dosecorrect treatment. Without antiretroviral of TDF and FTC immediately after delivery.treatment most people with HIV infection will 2. Giving daily nevirapine to the infant for sixeventually die of AIDS. weeks after birth and then continuing for as long as there is any breastfeeding.1-16 Is the HIV epidemic in South With the roll-out of the prevention of mother-Africa still expanding? to-child transmission (PMTCT) programme,Yes. Since 1990 the rate of HIV infection in the number of HIV-infected children shouldwomen attending state antenatal care clinics be greatly reduced.in South Africa has steadily climbed from lessthan 2% to almost 30% in 2008. South Africa The use of prophylactic antiretroviral drugshas one of the fastest-growing HIV epidemics reduces the risk of mother-to-child transmission.in the world, with one to two thousand peopleinfected every day. 1-19 What is the impact of HIV infection on society? South Africa has one of the fastest-growing HIV epidemics in the world. The epidemic of HIV infection is having a devastating impact on society in South Africa and other countries in sub-Saharan Africa.1-17 What is the risk of HIV crossing Since the start of the AIDS epidemic in Southfrom an infected mother to her infant? Africa, the average life expectancy has fallenThe risk of HIV crossing the placenta during from 60 to 45 years.pregnancy is 5% while the risk of HIV In Africa, most people with HIV infection are fe-infecting the infant during labour and vaginal male and most are from poor communities. Thisdelivery is 15%. Without HIV prophylaxis has a massive effect on families and increaseswith antiretroviral drugs the overall risk the risk of childhood under-nutrition and death,during pregnancy, labour and vaginal delivery even in HIV-negative children. The number ofis therefore 20%. orphans who have lost both parents to AIDS isThere is an additional risk of 15% if the mother rapidly rising. As a result of the ever-increas-practises mixed breastfeeding (breast milk ing number of deaths, ill people and homelessplus other liquids and solids) for two years. children, HIV infection is having an enormousThe total risk of mother-to-child transmission social and financial impact on all communities,(MTCT) in these breastfed infants is therefore and placing a strain on the health services.35%. The risk of breast milk transmission is5% for the first six months, 5% for the secondsix months and 5% for the second year. With SCREENING FORexclusive breastfeeding (breast milk only) forsix months, the risk is much lower. HIV INFECTION1-18 How can the risk of mother- 1-20 How is the clinical suspicionto-child infection be reduced? of HIV infection confirmed?The most effective method in women with By either detecting antibodies to the virus orHIV infection is to use antiretroviral drugs identifying part of the virus in the blood.
  • 5. HIV INFECTION 171-21 Should people be counselled The rapid test is the most common method usedbefore HIV testing? to screen people for HIV infection.People must be informed and counselledbefore blood tests are done to confirm NOTE Both ELISA and rapid tests are 99% accurateor exclude HIV infection. It should be if performed correctly and are confirmed with adocumented that the person consents to second test using a kit from another manufacturer.screening. It is considered unethical practiceto perform HIV screening tests without the 1-24 How is the ELISA test done?person’s permission. HIV screening is veryimportant as it is the ‘gateway to care’. 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.1-22 What tests are available to The laboratory should provide a result withinscreen for HIV infection? 24 hours. The result is either positive orA number of tests are available to screen negative. The disadvantage of the ELISA test ispeople for HIV infection: that it cannot be done at a clinic.1. Rapid test2. ELISA (Enzyme-Linked Immunosorbent 1-25 How is the rapid test done? Assay) test The great advantage of the rapid test is that it can3. PCR (Polymerase Chain Reaction test) test be done on a drop of blood in a clinic and blood4. P24 antigen test does not have to be sent to a laboratory. There are a number of manufacturers who provideSee skills workshop 6A for how to do a rapid test. rapid tests. They are very similar, but not exactly the same. If a rapid test is positive with one kit, NOTE HIV culture and testing for other HIV antigens it is important to repeat the test with another kit can also be done. These are expensive tests and from a different manufacturer to confirm that are only used in research or in cases where the the person really is HIV positive. diagnosis of HIV infection is difficult. The Western blot test is the most accurate test for detecting 1. If the first rapid test is negative, accept that virus antibodies, and is used in the laboratory the person is HIV negative. to make a diagnosis in difficult cases with 2. If two rapid tests on different kits are conflicting results with the ELISA or rapid test. positive, accept that the person is HIV positive.1-23 What are the rapid and 3. If the first test is positive and the second isELISA screening tests? negative, send blood to the laboratory forThese are commonly used blood tests to an ELISA test to decide whether the personscreen well people for HIV infection and also is HIV positive or negative.to confirm HIV infection in people who have In order to detect false-positive tests (the testsymptoms and signs. Both are cheap and very is positive but the patient is not infected withaccurate, and become positive if antibodies to HIV), all positive screening tests should beHIV are present. These tests do not determine repeated with another kit or with anotherwhether the actual virus is present, but rather type of test.the body’s response to the HIV infection.Therefore, they are highly reliable but indirect 1-26 What is the PCR test?tests for HIV. The rapid test is most commonlyused to screen for HIV infection. 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
  • 6. 18 ADULT HIVtest is very useful in screening infants younger the immune system. The normal CD4 count inthan 18 months for HIV infection as the rapid a healthy adult is above 500 cells/μl.and ELISA tests are unreliable to confirmHIV infection at this time, due to the possiblepresence of maternal antibodies. The CD4 count measures the degree of damage done by HIV to the immune system. NOTE The HIV DNA PCR test (qualitative) detects the presence of the virus within cells while the NOTE A low CD4 count must not be used HIV RNA PCR test (quantitative) measures the to diagnose HIV infection as there are amount of virus in the blood (viral load). The latter other causes of reduced CD4 cells. test may not be reliable to screen for HIV infection. 1-31 What is the viral load? The PCR test detects very small amounts of HIV The viral load is a measure of the amount of material in the blood. HIV in the blood. The higher the viral load, the faster the HIV is multiplying. A high viral1-27 What is the p24 antigen test? load indicates that there is a lot of HIV in the blood (and other body secretions). Viral loadP24 antigen is part of the virus. The p24 antigen is usually expressed as RNA copies/ml.test detects this HIV material in the blood. Theultrasensitive p24 antigen test is very accurate. The viral load is a measure of the amount of HIV1-28 When do these tests become in the blood.positive if a person is infected with HIV?They may become positive as early as twoweeks after infection, but most are reliable CLINICAL PRESENTATIONfrom six weeks after infection. OF HIV INFECTION1-29 What is the window period? 1-32 What are the threeThis is the period of time between infection phases of HIV infection?and the test becoming positive. During thistime the test may give a false-negative result HIV infection can be divided into three phases.(the patient is infected with HIV but the test 1. Acute seroconversion illness (which onlyis still negative). For most tests, the window occurs in 50% of people)period lasts up to six weeks. Rarely, the 2. The latent, silent, asymptomatic phasewindow period may be longer, up to three 3. The chronic disease when HIV infectionmonths. With new, highly sensitive tests the becomes symptomaticwindow period is shortening. 1-33 What is acute seroconversion illness?1-30 What is the CD4 count? In response to infection with HIV, the immuneCD4 cells are lymphocytes that play a very system produces antibodies against the virus.important role in the normal functioning of Unfortunately these antibodies fail to kill all thethe immune system. HIV attaches to CD4 HIV. At the time that HIV antibodies appear incells and kills them. As a result, the number of the blood (seroconversion) about 50% of peopleCD4 cells gradually falls as the HIV infection develop a flu-like illness which lasts a few daysprogresses, and more and more CD4 cells are or weeks. Acute seroconversion illness presentskilled. Therefore the CD4 count is the best two to six weeks after infection with HIV.measure of the degree that HIV has damaged
  • 7. HIV INFECTION 19During acute seroconversion illness the viral are present in the blood and other body fluids,load is very high and the CD4 count may be and the person is very infectious to others.temporarily depressed. The screening tests forHIV may still be negative at the time of acuteseroconversion illness, and only becomes People are very infectious during the first weekspositive a few weeks later. of HIV infection. 1-36 How are patients with acute Infection with HIV may cause acute seroconversion illness managed? seroconversion illness. The patients are managed symptomatically NOTE Patients who develop severe acute with antipyretics (e.g. paracetamol) for fever. seroconversion illness usually progress to AIDS There is no role for antiretroviral treatment in faster than those who are asymptomatic while seroconversion illness. seroconverting. They should be closely followed up. 1-37 What is the latent phase1-34 What are the common features of HIV infection?of acute seroconversion illness? HIV infection and seroconversion are followedThe common features of acute seroconversion by a latent period when the person feels well.illness are: During this phase many people are not aware1. Fever that they are HIV infected. Although there2. General tiredness are usually no, or few, clinical signs during3. Headache the latent phase of HIV infection, generalised4. Cough or sore throat lymphadenopathy is common.5. Muscle or joint pains During the latent phase the viral load is low6. Nausea, vomiting or diarrhoea and the CD4 count is normal or only mildly7. Enlarged lymph nodes (lymphadenopathy) depressed.8. A measles-like rash9. Oral or genital ulcers Most people with asymptomatic HIV infection areThe above signs and symptoms are similar not aware that they have been infected with HIV.to those found in glandular fever (infectiousmononucleosis). 1-38 How long does the latent phase last? NOTE Some people also develop neurological Usually this silent, asymptomatic period lasts complications such as meningitis, encephalitis five to ten years in adults but it may last for or neuropathy. Typically the lymphocyte and CD4 counts are low during the acute illness. as long as 15 years before the signs of AIDS appear (‘slow progressors’). Occasionally, HIV- infected people progress rapidly to AIDS (‘fast Acute seroconversion illness is often the first sign progressors’). of HIV infection. The asymptomatic latent phase usually lasts five1-35 Are people with seroconversion to ten years in adults.illness infectious to others?Yes, during the first few weeks of HIV 1-39 What is symptomatic HIV infection?infection, especially if the person developsseroconversion illness, large amounts of virus When patients who have been clinically well during the latent (asymptomatic) phase of HIV infection become ill, they are said to have
  • 8. 20 ADULT HIVsymptomatic HIV infection. The symptoms production of antibodies increases in responseand signs of symptomatic HIV infection only to the HIV infection. Antibodies, togetherpresent when the immune system is no longer with CD4 cells, attempt to control the amountable to protect the person from a wide range of of virus in the body and the levels of HIV inviral, bacterial, fungal and parasitic infections the blood decreases. Eventually (within six(opportunistic infections). months) a balance is reached between the production and destruction of HIV. This is known as the viral set point. Clinical illness only occurs late in the course of HIV infection. With the onset of symptomatic HIV infection (constitutional symptoms) the CD4 count falls and the level of virus increases and becomes1-40 When is symptomatic HIV very high with AIDS (opportunistic infections).infection called AIDS?Once patients develop severe opportunistic The level of virus in the blood is very high sooninfections or malignancies typically associatedwith HIV infection. This only occurs when the after infection and again with the developmentimmune system has been severely damaged. of AIDS.Patients who are generally well or only mildlyill with HIV infection do not yet have AIDS. NOTE A high viral set point carries a poor prognosis of rapid progression to AIDS, as it indicates failure by the immune system1-41 How do the viral load, antibody to control massive multiplication of HIV.levels and CD4 count change duringthe course of HIV infection? 1-42 What clinical signs suggestThe level of virus in the blood (viral load) rises the patient has HIV infection?very rapidly within weeks of infection due to 1. Unexplained weight lossthe extremely high rate of viral multiplication. 2. Unexplained fever or night sweatsThis temporarily depresses the CD4 count. The 3. Generalised lymphadenopathy CD4 count Viral load Death 1000 log6 Opportunistic CD4 infections (cells/mm3) Viral load 600 log4 Constitutional symptoms 200 log2 6 12 6 9 12 Time (weeks) Time (years)Figure 1-1: The changes in viral load, CD4 count and clinical features of HIV infection
  • 9. HIV INFECTION 214. A variety of skin rashes 1-45 What are the clinical signs5. Mouth infections of stage 2 HIV infection?6. Chronic diarrhoea Patients with stage 2 HIV infection have7. Repeated respiratory infections or chronic repeated minor problems. Skin rashes and cough minor mouth problems are very common.8. Signs of opportunistic infections and other Often there is some weight loss and mild HIV-related illnesses such as malignancies diarrhoea can be a problem. Patients withOften painless, generalised lymphadenopathy these early stages of HIV infection can usuallyin an otherwise healthy person is the first continue their daily activity.clinical sign of HIV infection. Patients with stage 2 HIV infection have repeated minor clinical problems.CLINICAL STAGES OFHIV INFECTION 1-46 What are the features of stage 3 HIV infection?1-43 What is the natural Common features are unexplained weightprogression of HIV infection? loss, fever, oral candidiasis and diarrhoea. Pulmonary TB and severe bacterial infectionsThe progression of early to advanced HIV indicate stage 3 infection. These patientsinfection usually follows a recognisable pattern feel generally unwell and are no longer ablewhich depends on the degree of damage to to continue with their usual daily activities.the immune system. The progression of HIV Most of these patients will improve if theirinfection has been divided into 4 clinical opportunistic infections are treated.stages by the World Health Organisation(WHO). Patients advance through stages 1 to4 as their CD4 count falls. Pulmonary TB and serious bacterial infections are common in patients with stage 3 HIV infection. The clinical signs become worse and the CD4 count falls as patients progress from stage 1 to 1-47 How would one recognise a stage 4 HIV infection. patient with stage 4 HIV infection? Marked weight loss continues and manyA table of the World Health Organisation patients are bedridden. Severe opportunistic(WHO) stages of HIV infection is given at the infections such as oesophageal candidiasis,end of this unit. extrapulmonary TB, pneumocystis pneumonia, cryptococcal meningitis and toxoplasmosis are1-44 What are the clinical signs common. Anaemia and malignancies associatedof stage 1 HIV infection? with HIV infection are also common. Patients with stage 4 disease are regarded as havingPatients with stage 1 HIV infection are well and AIDS. Response to antiretroviral treatment isasymptomatic but almost all have persistent, usually good. Without treatment many will diegeneralised lymphadenopathy, especially in the within months.neck, axilla and groin. Acute seroconversionillness is also included in stage 1. Therefore,stage 1 starts at the time of infection. Serious opportunistic infections are common when stage 4 HIV infection (AIDS) is reached. People with stage 1 HIV infection are generally well.
  • 10. 22 ADULT HIV1-48 What are the features of terminal AIDS? as multiple, vertical white stripes along the side of the tongue. Its presence indicatesAdditional opportunistic infections such immune depression.as CMV retinitis and avium TB can occur. 3. Aphthous ulcers. These are very painful,Severe wasting and dementia are common. shallow ulcers that can occur anywhere inThese patients are seriously ill, usually with the mouth.a CD4 count below 50 cells/μl. Response 4. Herpes simplex ulcers may also affect theto antiretroviral treatment is often poor as mouth and are also painful.the immune system has been very seriously 5. Gum infections around the base of thedamaged by HIV. Without treatment most teeth which may cause pain and bleeding.patients rapidly die. 6. Kaposi’s sarcoma. NOTE Oral hairy leucoplakia is due toCOMMON COMPLICATIONS infection with the Epstein-Barr virus.OF HIV INFECTION Severe oral infections which prevent the patient eating and drinking, and do not improve in a few days, may lead to further weight loss,1-49 What is an AIDS-defining illness? dehydration and under-nutrition. These patientsA serious clinical condition which is very should be referred to a special HIV clinic.uncommon in HIV-negative people and yetseen commonly in patients with advanced 1-52 What skin rashes are commonlyHIV infection. Severe opportunistic infections seen in patients with HIV infection?and malignancies in HIV-positive patients Many different skin rashes are seen in HIV-are AIDS-defining illnesses. Common AIDS- infected patients and a skin rash may be one ofdefining infections include oesophageal the earliest signs of a depressed immune system:candidiasis, and infections with pneumocystis,cryptococcus and toxoplasmosis. 1. Pruritic papular eruption (PPE or ‘itchy bump disease’)1-50 Is pulmonary tuberculosis 2. Seborrhoeic dermatitisan AIDS-defining illness? 3. Fungal infections of the skin, hair and nails 4. Molluscum contagiosumAlthough pulmonary TB is common in 5. Wartspatients with HIV infection, and indicates 6. Impetigo and folliculitisstage 3, it also occurs in HIV-negative people 7. Severe, extensive scabiesand it is therefore not an AIDS-defining 8. Psoriasisinfection. In contrast, extrapulmonary TB is 9. Shinglesrare in HIV-negative people and is thereforean AIDS-defining illness. Rashes may also be due to drugs used in antiretroviral treatment (e.g. nevirapine) or drugs used to treat opportunistic infections1-51 What infections of the mouth (e.g. co-trimoxazole). Drug reactions are moreare common with HIV infection? common in HIV-infected patients than inThe mouth and tongue are commonly affected people who are not HIV infected.when the immune system is damaged by HIVinfection. 1-53 What is characteristic of rashes1. The commonest mouth condition is oral in HIV-positive patients? candidiasis (thrush). Rashes are often severe, chronic or recurrent,2. Oral hairy leucoplakia. This is usually and respond poorly to standard treatment. asymptomatic and painless, and presents Rashes frequently are atypical and usually do
  • 11. HIV INFECTION 23not resolve spontaneously. Previous rashes may Kaposi’s sarcoma, non-Hodgkin’s lymphoma andbecome worse with the development of HIV cervical cancer are more common in patientsinfection, e.g. psoriasis, acne and eczema. Withantiretroviral treatment most rashes disappear. with AIDS.1-54 What is pruritic papular eruption (PPE)? 1-57 What is Kaposi’s sarcoma?This is very common in patients with HIV This is the most common cancer complicatinginfection and presents with a severe itch and AIDS.scattered pigmented papules, especially on Kaposi’s sarcoma usually presents with multiplethe trunk and limbs. It is difficult to treat and pink or purple patches in pale skins and brownresponds poorly to topical steroids and anti- or black patches in dark skins, or nodulesitch agents. (bumps) on the skin, especially the face, trunk and legs. The mouth may also be involved,1-55 What is wasting disease? especially the hard palate. The prognosis is poorThis is a common presentation of AIDS in advanced cases when organs such as the gut,in patients in Africa. Weight loss is severe lungs and lymph nodes are affected (visceraland associated with chronic diarrhoea. The Kaposi’s sarcoma). Non-visceral (skin) Kaposi’spatients feel weak and have fever. All patients sarcoma is usually not life-threatening, but canwith unexplained weight loss must be screened become extensive and have an unacceptablefor HIV infection. appearance. The patches and nodules often improve with antiretroviral treatment. Cancer treatment is usually only given to severe cases. All patients with unexplained weight loss must All patients with Kaposi’s sarcoma should be be screened for HIV infection. referred to a special HIV clinic. NOTE Severe wasting is due to anorexia, diarrhoea, malabsorption and infections Kaposi’s sarcoma presents with purple or brown as well as oral conditions which make skin patches or nodules. eating painful (e.g. thrush or herpes). NOTE Kaposi’s sarcoma is associated1-56 What malignancies are with the Human Herpes 8 virus whichassociated with AIDS? may be sexually transmitted.Many patients with AIDS develop some form of 1-58 What is non-Hodgkin’s lymphoma?cancer. Viral infections and a damaged immunesystem are probably the cause. Of interest is that This is the second commonest cancer in AIDSonly some cancers are more common in AIDS patients. Non-Hodgkin’s lymphoma is a grouppatients. However, the progression of other of different types of lymphoma which oftencancers common in the general population is progress rapidly. Therefore, early diagnosis andmore rapid in AIDS patients. Cancers more treatment are important. Lymphoma usuallycommon in patients with AIDS are: presents with large firm lymph nodes at one or more sites, or abdominal masses together1. Kaposi’s sarcoma with weight loss and unexplained fever. Sites2. Non-Hodgkin’s lymphoma other than lymph nodes can be involved,3. Cervical cancer especially the brain, liver, bone marrow andPatients with any of these cancers must be gut. Non-Hodgkin’s lymphoma of the braintested for HIV infection. may present with a wide range of neurological conditions including headaches, convulsions, confusion and memory loss. Any patient with
  • 12. 24 ADULT HIVa suspected lymphoma must be referred for obvious when the patient has AIDS, especiallyinvestigation. The prognosis is usually poor. in the advanced stage. Common signs of HIV encephalopathy are: Lymphoma of the brain may present in AIDS 1. Poor concentration and short-term memory patients with a wide range of neurological signs. loss, eventually leading to dementia 2. Personality changes with depression, NOTE Most lymphomas in AIDS patients apathy, withdrawal or irritability are of B cell origin and associated 3. Weakness, tremors or clumsiness with Epstein-Barr virus infection. Often there are no obvious abnormalities on examination of the central nervous1-59 What is the presentation system early in the disease. The worseningof cervical cancer? of HIV encephalopathy can be slowed withCervical cancer is common in women with antiretroviral treatment.AIDS. In the early stages there are usually no NOTE CT and MRI scans with HIV encephalopathysymptoms or signs. Therefore all HIV-positive reveal cortical atrophy. In contrast, scans inwomen must have an annual screen with a progressive multifocal leucoencephalopathyPAP smear or cervical inspection for cancer. (PML) due to Creutzfeldt-Jakob infection show areas of white matter demyelination. All HIV-positive women must be screened regularly for cervical cancer. WHO STAGING SYSTEM FOR NOTE The human papilloma virus, which HIV INFECTION IN ADULTS is associated with cervical cancer, is sexually transmitted and more AND ADOLESCENTS common in HIV-positive women. Clinical stage 11-60 What neurological conditionsare associated with AIDS? • Seroconversion illness • Asymptomatic infectionMany neurological complications are seen in • Persistent generalised lymphadenopathypatients with AIDS. Neurological problems • Normal daily activitymay also be due to drug side effects (e.g.peripheral neuropathy with isoniazid (INH)). Clinical stage 21. HIV encephalopathy • Weight loss up to 10%2. Cryptococcal meningitis • Minor oral problems (recurrent mouth3. Bacterial meningitis ulcers)4. Tuberculous meningitis or tuberculoma • Skin rashes5. Toxoplasmosis • Recurrent upper respiratory tract6. Non-Hodgkin’s lymphoma infections • Herpes zoster (shingles) NOTEThe spinal cord, peripheral nerves • Symptomatic, but daily activity normal and muscles can also be involved. Clinical stage 31-61 What is HIV encephalopathy? • Weight loss of more than 10%HIV infects the brain early in the course of • Chronic diarrhoea for more than oneHIV disease. Signs of HIV encephalopathy monthusually develop slowly and become more • Prolonged fever for more than one month
  • 13. HIV INFECTION 25• Oral candidiasis demyelinating polyneuropathy (CIDP) non-• Oral hairy leucoplakia responsive to immunomodulatory therapy• Pulmonary tuberculosis• Severe bacterial infection (e.g. meningitis)• Bedridden for less than 50% of the day in CASE STUDY 1 the past month A healthy pregnant woman is found to be HIVClinical stage 4 (AIDS) positive. She asks how she probably became infected and whether HIV infection is common• HIV wasting syndrome in pregnant women. She asks the nurse• Pneumocystis pneumonia whether she will pass HIV on to her infant.• Oesophageal candidiasis• Toxoplasmosis of the brain• Cryptococcal meningitis 1. How is HIV usually transmitted• Diarrhoea due to Cryptosporidiosis or in South Africa? Isosporiasis By penetrative heterosexual vaginal intercourse.• Cytomegalovirus (CMV) disease The risk of HIV transmission is highest with• Extrapulmonary TB anal intercourse in both men and women. The• Disseminated herpes simplex risk of HIV infection is much less with oral• HIV encephalopathy sexual contact. Kissing is probably safe.• Kaposi’s sarcoma, lymphoma or invasive cervical cancer 2. Can HIV be spread by• Confined to bed for more than 50% of the normal social contact? day No. HIV is not spread by touching, holdingAdditional clinical criteria hands, hugging, coughing, sneezing, usingindicating stage 4 disease swimming pools, toilet seats or sharing cooking, drinking and eating utensils. NOTE These patients may only be initiated on ART following consultation and recommendation from an infectious disease/ART unit specialist 3. Can a person with HIV infection or specialist in these listed pathologies. appear perfectly healthy? • Idiopathic thrombocytopenic purpura (ITP) Many people feel well without any clinical signs in spite of having asymptomatic HIV • Thrombotic thrombocytopenic purpura (TTP) infection for many years. • Autoimmune haemolytic anaemia • HIV-associated nephropathy 4. Are they infectious during this time? • HIV-associated cardiomyopathy • Severe HIV neuropathy or HIV myelopathy Yes. The danger is that many infectious people who feel well do not know that they have HIV • Refractory apthous ulceration infection. • All malignancies (unless early malignancy that is surgically resectable with low relapse risk) 5. How common is HIV infection in • MDR TB (after adherence counselling and pregnant women in South Africa? assessment has been done and patient is seen to be a suitable candidate) In 2008, almost 30% of pregnant women • HIV-associated vasculopathy attending state antenatal clinics were HIV • Diffuse infiltrative lymphocytosis syndrome positive. This has increased from less than 2% (DILS) with severe symptoms in 1990. • Acute inflammatory demyelinating polyneuropathy (AIDP)/chronic inflammatory
  • 14. 26 ADULT HIV6. What is the risk that this woman period usually lasts up to six weeks. Somewill pass HIV to her infant? people with acute seroconversion illness may still be in the window period.With a vaginal delivery and no antiretroviralprophylaxis, the risk of HIV transmissionis 20%. The additional risk of mixed 5. How does HIV cause disease?breastfeeding is 15%. The risk is less with By killing CD4 cells and, thereby, damagingexclusive breastfeeding. With antiretroviral the immune system. As a result the body isprophylaxis and exclusive bottle feeding the unable to protect itself from a wide range ofoverall risk is less than 5%. viral, bacterial, fungal and parasitic infections. 6. What effect is HIV havingCASE STUDY 2 on society in Africa? The HIV epidemic is having a devastatingA young woman presents with fever, a sore effect on society. It is estimated that six millionthroat, enlarged lymph nodes and a rash. She South Africans are HIV positive. Most arealso feels generally unwell. female. The life expectancy for South Africans has fallen from 60 to 45 years.1. Could these signs and symptomsbe due to HIV infection?The presentation is typical of the acute CASE STUDY 3seroconversion illness which occurs in 50% ofHIV infected people. This condition usually A 25-year-old man is seen at a primary-presents two to six weeks after HIV infection care clinic with herpes zoster which isand may be misdiagnosed as glandular fever. very painful. He has also lost some weight and complains of recurrent mouth ulcers.2. Should she be treated with On examination he has generalisedantiretroviral drugs? lymphadenopathy and typical pruritic papular eruption. His HIV test was positive four yearsNo. Usually symptomatic treatment (e.g. ago when he was screened at work. He is stillparacetamol for fever) is all that is needed. able to continue working.3. How can the clinical suspicion 1. How would you grade the clinicalof HIV infection be confirmed? stage of HIV infection in this patient?By finding a positive screening test (usually He should be graded as stage 2. Herpesa rapid test). The rapid test can be done zoster, recurrent aphthous mouth ulcers andin a primary-care clinic. A negative test skin rashes with mild weight loss are seen inmay be repeated after two weeks if acute stage 2 HIV infection. The rapid test confirmsseroconversion illness is suspected. All the clinical diagnosis. Patients in stage 2 canpatients must be informed and counselled and usually continue working.give consent before a rapid test is done. 2. What would the staging be if he only had4. What is the window period? lymphadenopathy and was generally well?The period between HIV infection and a Stage 1.screening test becoming positive. In thewindow period the HIV blood test may befalsely negative (the test is negative but theperson is infected with HIV). The window
  • 15. HIV INFECTION 273. What is pruritic papular eruption? 1. What is the most likely cause of the cough and night sweats?Pruritic papular eruption (PPE or ‘itchybump disease’) is common in patients with She almost certainly has pulmonarysymptomatic HIV infection. It presents with tuberculosis.scattered pigmented papules (bumps) whichare very itchy. The rash is usually seen on the 2. What condition causes multiple,trunk and limbs, it is difficult to treat and painless purple patches in aresponds poorly to topical steroids. patient with HIV infection? Kaposi’s sarcoma. These patients may have4. What other skin rashes are common multiple purple or brown skin patches orin patients with stage 2 HIV infection? nodules. The mouth, lymph nodes, lungs andSeborrhoeic dermatitis, molluscum gut may also be involved.contagiosum, warts, scabies and psoriasis.Bacterial and fungal infections are also very 3. Why is she having difficulty swallowing?common. The finding of oral thrush (oral candidiasis) and difficulty swallowing suggests that she5. What are common causes of a painful may have oesophageal candidiasis.mouth in patients with HIV infection?A painful mouth is a common complaint 4. Does she have AIDS?in patients with HIV infection. Recurrentaphthous ulcers, oral candidiasis, herpes Yes. Both Kaposi’s sarcoma and oesophagealulcers and infected gums are frequently seen. candidiasis are AIDS-defining conditions asKaposi’s sarcoma and oral hairy leucoplakia they are very rare in people with a normalare usually not painful. immune system (i.e. they are opportunistic infections). She would therefore be graded as having stage 4 HIV infection – i.e. AIDS.6. How long is the latent period?This varies between people. However, most 5. Is pulmonary TB an AIDS-defining illness?people with HIV infection remain well(asymptomatic) for about ten years (except for No. If she only had pulmonary TB as apossible acute seroconversion illness) before complication of being HIV infected she woulddeveloping clinical signs and symptoms of be graded as stage 3. Extrapulmonary TBHIV infection. would make her stage 4. 6. What malignancies areCASE STUDY 4 associated with AIDS? Malignancies associated with AIDS areA woman presents with a cough and night Kaposi’s sarcoma, non-Hodgkin’s lymphomasweats for six weeks and a number of and cervical cancer.painless, purple patches on her skin. She hasoral thrush and difficulty swallowing. Herhusband died of AIDS the year before. Ontesting she is HIV positive.