Medical monitoring: Clinical monitoring and laboratory tests

Transcription

1 medical monitoring: clincial monitoring and laboratory tests: 1 medical monitoring: clinical monitoring and laboratory tests Medical monitoring: Clinical monitoring and laboratory tests Aims This section provides information on clinical and laboratory monitoring of patients with HIV. It includes the latest World Health Organisation recommendations on monitoring antiretroviral therapy in resource-limited settings. It discusses baseline clinical assessments and clinical monitoring for effectiveness and toxicities of antiretroviral therapy. It also discusses laboratory tests that are used as indicators of the progress of HIV disease and of antiretroviral treatment: CD4, viral load, and other blood tests. This section also covers a range of other blood tests and monitoring procedures that are can be used to assess general health when resources permit, although these may not be available in some limited resources settings. Related modules: CD4 cell counts Viral load testing Monitoring side effects of treatment Tests available at central hospitals Intended audience Doctors new to HIV care Medical/clinical officers (select relevant slides on clinical diagnosis and side effect monitoring) Nurses (select relevant slides on clinical diagnosis and side effect monitoring)

2 medical monitoring: clincial monitoring and laboratory tests: 2 Topics covered Medical monitoring Clinical monitoring Laboratory monitoring WHO guidelines on monitoring antiretroviral therapy in resource-limited settings. Diagnosis of HIV infection Initial assessment of an HIV-positive patient Diagnosing STIs, TB and other co-infections

3 medical monitoring: clincial monitoring and laboratory tests: 3 Slide 1 Purpose of monitoring Check on the physical, psychological and emotional condition of the patient Detect other treatable conditions Identify when a patient needs to start antiretroviral or other treatment Indicate the long term outlook for a patient Show whether a patient is at risk for unwanted effects (toxicity) of treatment clinical monitoring and laboratory tests: 1 Purpose of monitoring HIV causes gradual changes in the human body. If HIV is not treated, these changes can lead to worsening health and eventually to AIDS. Keeping track of such changes in the body is known as medical monitoring, which depends on clinical assessments and laboratory tests. Medical monitoring should begin as soon as a person has a positive HIV antibody test. The purpose of monitoring is to: Check on the physical, psychological and emotional condition of the patient Detect other treatable conditions Identify when a patient needs to start antiretroviral or other treatment Indicate the long term outlook for a patient Show whether a patient is at risk for unwanted effects (toxicity) of treatment Monitoring must start with a clinical assessment comprising: detailed medical history including length of time since the diagnosis of HIV infection, other infections such as TB or STIs, chronic conditions such as diabetes or lung problems, hospitalisation or surgery, current medications and current symptoms social and economic status including family, sources of support, sexual partners, access to health care, transport and finance for medical expenses, living conditions and availability of food and nutrition detailed physical examination including specific areas for HIV and other related infections, weight, neurological status baseline laboratory tests or investigations

4 medical monitoring: clincial monitoring and laboratory tests: 4 The first clinical assessment establishes a baseline so that subsequent changes in a patient s condition can be more readily recognized. When the patient has begun antiretroviral treatment, follow-up assessments can show whether that person is responding to therapy or developing side effects. Valuable diagnostic and monitoring information can be gained without performing laboratory tests. For example, observation of signs of some opportunistic infections may indicate that the patient needs to start antiretroviral therapy. However, some patients do not need antiretroviral treatment immediately. Careful clinical monitoring can assess a patient s risk of progression and help in planning the patient s long-term care.

5 medical monitoring: clincial monitoring and laboratory tests: 5 Slide 2 Laboratory monitoring before treatment Basic Antibody tests, red blood cell and white blood cell counts and pregnancy tests. These tests can be done in any medical laboratory. Better equipped lab CD4 cell count to monitor health of immune system Viral load test to monitor amount of virus in blood clinical monitoring and laboratory tests: 2 Laboratory monitoring before treatment A wide variety of laboratory tests are used in medical monitoring. Some are used to confirm an HIV diagnosis, or to detect co-infections such as tuberculosis. Various blood tests directly measure viral activity or monitor HIV-related changes in the function of the immune system. Other tests are used to estimate the risk of toxicity due to antiretroviral treatment and can be used to guide the choice of treatment. The setting and the availability of technical and financial resources will determine which tests can be used. The minimum tests required for laboratory monitoring before or during antiretroviral therapy are: HIV antibody tests, red blood cell and white blood cell counts and pregnancy tests. These tests can be done in any medical laboratory. If resources are better, a CD4 blood test should be done, which shows how much damage HIV has caused to the immune system, or if the immune system is starting to recover as a result of treatment. The count is low when the immune system is damaged and should gradually increase when the system is recovering. In well-resourced hospital laboratories, a viral load test can be used to show how active the virus is in a person's body, and to predict how quickly disease is likely to appear. It increases when the virus is active and should decrease as a result of treatment. These tests are very useful tools for predicting the future course of HIV and the risk of developing AIDS. However, they are at present too expensive to use in most resource-limited settings, especially those with high HIV prevalence. CD4 and viral load tests may be used in a limited way, for example if clinical assessments and basic blood tests do not provide adequate information for treatment decisions. Ongoing research is progressing towards cheaper and more widely available CD4 and viral load tests, or low cost alternatives that can be used in their place. Lack of access to laboratory tests should not be a barrier to providing antiretroviral therapy to patients with AIDS. The following section summarises the World Health Organization (WHO) recommendations for monitoring antiretroviral therapy in resource-limited settings.

6 medical monitoring: clincial monitoring and laboratory tests: 6 Slide 3 Monitoring in resource-limited settings WHO prioritise currently available tests into four categories: Absolute minimum tests necessary before beginning ARV therapy: HIV antibody test. Haemoglobin or haematocrit level to screen for anaemia. Basic tests used to monitor ARV therapy (preferable but not essential): White blood cell count. Total lymphocyte count. ALT/AST level for liver function. Serum creatinine for kidney function. Serum glucose. Pregnancy test for women. Desirable tests: Bilirubin, amylase, serum lipids and CD4 count. Optional tests: Viral load testing clinical monitoring and laboratory tests: 3 Monitoring in resource-limited settings WHO recommends that the basic clinical assessment should include documentation of medical history, identification of current and past HIV related illnesses, identification of co-existing medical conditions that may influence choice of therapy (such as TB or pregnancy), as well as current symptoms and physical signs (such as weight and temperature). Where laboratory monitoring is limited, close clinical monitoring is crucial for the provision of safe and effective ART. Laboratory tests provide additional information that is useful when considering ART or monitoring its progress. In order to facilitate the scale up of antiretroviral (ARV) therapy in resource-limited settings, WHO prioritises laboratory tests into 4 categories: Absolute minimum tests, which are essential for introduction of ARV therapy; these include an HIV antibody test to confirm HIV infection and a blood test measuring haemoglobin or haematocrit levels to screen for anaemia, which may be due to nutritional deficiencies or treatable parasitic diseases and is a risk factor for side effects of antiretroviral therapy, especially zidovudine, which often causes anaemia when taken by people with HIV. Basic tests are used to provide effective monitoring of most ARV regimens and are needed to identify potential toxic reactions and then to trigger changes in drug regimens. Basic laboratory tests were not considered by WHO to be absolutely essential to start an ART programme, but they need to be made available as soon as resources allow. They include: White blood cell count and differential to permit assessment of neutropenic side-effects of ARV therapy and a total lymphocyte count; when combined with the WHO staging system these tests provide useful information about prognosis; Serum alanine or aspartate aminotransferase level, to assess the possibility of hepatitis co-infection and to monitor for toxicity to the liver; Serum creatinine and/or blood urea nitrogen (to assess baseline kidney function);

7 medical monitoring: clincial monitoring and laboratory tests: 7 Serum glucose (blood sugar levels) Pregnancy tests for women. Anaemia prior to starting ARV treatment places patients at risk of worsening anaemia if AZT is included in the drug combination. Full blood counts for red cells and white cells can also detect general bone-marrow suppression. Liver function tests are important, since a number of ARVs can cause liver damage. Hepatitis, if present, also increases the risk of side effects - especially from protease inhibitors, which are eliminated from the body through the liver. Peripheral neuropathy is a risk associated with treatment using isoniazid (preventive treatment for tuberculosis) and with the antiretrovirals d4t (stavudine), ddi (didanosine) and ddc (zalcitabine). Peripheral neuropathy should be assessed before a person starts treatment and at regular intervals while a person is on treatment with drugs linked to it. Tests for pregnancy are needed, for women to be given options for their own treatment and also to prevent transmission of HIV to a child. If a woman is pregnant, nevirapine or other drugs may be preferred to efavirenz, since efavirenz has been found in animal studies to cause birth defects.

8 medical monitoring: clincial monitoring and laboratory tests: 8 Slide 4 Symptoms that indicate need for HIV test Unexplained weight loss or loss of appetite Fever; especially at night Chronic watery diarrhoea; Swollen lymph nodes (generalised lymphadenopathy); Persistent skin disorders including skin rashes, itching, herpes simplex ulcers, herpes zoster (shingles), seborrhoeic dermatitis, warts; anal itching or discomfort. Neurological problems including dementia in patients less than 50 years old, or sudden onsets of unexplained psychosis, peripheral neuropathy, and Bell s palsy; Persistent cough, breathing problems or pneumonia; Severe or recurrent bacteraemias especially pneumococci and salmonellae Tuberculosis OR Development of any AIDS-defining illness clinical monitoring and laboratory tests: 4 Symptoms that indicate need for HIV test HIV infection is often not diagnosed until a patient seeks medical attention for symptoms or opportunistic infections related to HIV infection. Thus, it is particularly important to recognise the clinical signs of HIV infection. An HIV test should be considered if a patient has any of the opportunistic infections related to HIV infection or has one or more of the following conditions: unexplained weight loss or loss of appetite fever; especially at night chronic watery diarrhoea; swollen lymph nodes (generalised lymphadenopathy); persistent skin disorders including skin rashes, itching, herpes simplex ulcers, herpes zoster (shingles), seborrhoeic dermatitis, warts; anal itching or discomfort. neurological problems including dementia in patients less than 50 years old, or sudden onsets of unexplained psychosis, peripheral neuropathy, and Bell s palsy; persistent cough, breathing problems or pneumonia; severe or recurrent bacteraemias especially pneumococci and salmonellae. or development of any AIDS-defining illness

9 medical monitoring: clincial monitoring and laboratory tests: 9 Patients with HIV are often co-infected with tuberculosis, but not always. In high prevalence settings up to 60% or more of HIV-positive people also have TB. TB patients should always be strongly encouraged to have an HIV antibody test. HIV patients should always be tested for tuberculosis, but if they have extra-pulmonary or disseminated tuberculosis a sputum or tuberculin test for TB may show a false negative. Further tests and X-rays may be necessary to show whether curative or preventive treatment for TB is required. Curative TB treatment is usually given for six months, before starting antiretroviral treatment.

10 medical monitoring: clincial monitoring and laboratory tests: 10 Slide 5 AIDS-defining illnesses Candida in the oesophagus, trachea, bronchi or lungs. Invasive cervical cancer. Coccidiodomycosis. Cryptococcus outside the lungs. Cryptosporidiosis with diarrhoea lasting for more than one month. CMV disease outside the liver, spleen or lymph nodes. CMV retinitis. Herpes simplex virus involving the lungs or oesophagus. HIV-related encephalopathy. Chronic intestinal isosporiasis lasting longer than one month. Kaposi s sarcoma. Burkitt s, immunoblastic or primary brain lymphoma. Widespread MAI, M kansasii or other species. Pneumocystis carinii pneumonia (PCP). Recurrent bacterial pneumonia. Progressive multifocal leukoencephalopathy. Recurrent salmonella septicemia. Toxoplasmosis of the brain. HIV wasting syndrome. clinical monitoring and laboratory tests: 5 AIDS-defining illnesses Candida in the oesophagus, trachea, bronchi or lungs. Invasive cervical cancer. Coccidiodomycosis. Cryptococcus outside the lungs (eg cryptococcal meningitis). Cryptosporidiosis with diarrhoea lasting for more than one month. CMV disease outside the liver, spleen or lymph nodes (eg CMV disease in the oesophagus or the gastrointestinal tract). CMV retinitis. Herpes simplex virus involving the lungs or oesophagus. HIV-related encephalopathy. Chronic intestinal isosporiasis lasting longer than one month. Kaposi s sarcoma. Burkitt s, immunoblastic or primary brain lymphoma. Widespread Mycobacterium avium intracellulare (MAI), M kansasii or other species. Pneumocystis carinii pneumonia (PCP). Recurrent bacterial pneumonia. Progressive multifocal leukoencephalopathy. Recurrent salmonella septicemia. Toxoplasmosis of the brain. HIV wasting syndrome.

11 medical monitoring: clincial monitoring and laboratory tests: 11 Slide 6 Conditions commonly suggestive of HIV disease

12 medical monitoring: clincial monitoring and laboratory tests: 12 Slide 7 WHO staging system clinical stage one Asympotmatic infection stage one Acute retroviral infection Persistent generalised lymphadenopathy Performance Stage 1: Asymptomatic, normal activity clinical monitoring and laboratory tests: 7 WHO staging system clinical stage one Patients in stage One are either recently infected, or will have no symptoms. Symptoms of the acute retroviral syndrome, also known as HIV seroconversion illness, include: fever and rash together fever aches and pains oral ulceration fatigue nausea Persistent generalised lymphadenopathy refers to swollen lymph glands. During the earlier stages of the disease, most of the HIV in a person s body is concentrated in the lymph glands in the neck, under the arms and possibly in the groin. These glands may become vsibly swollen, and will often feel swollen when checked in the normal way.

13 medical monitoring: clincial monitoring and laboratory tests: 13 Slide 8 WHO staging system clinical stage two Herpes zoster within previous 5 years Unintentional weight loss <10% body weight stage two Minor mucocutaneous manifestations (for example, dermatitis, prurigo, fungal nail infections, angular cheilitis) Recurrent upper respiratory tract infections Performance Stage 2: Symptoms, but nearly fully ambulatory. clinical monitoring and laboratory tests: 8 WHO staging system clinical stage two The risk of developing Herpes zoster (shingles) increases as HIV causes more damage to the immune system. An attack of shingles may suggest HIV disease, particularly if the individual has experienced other minor health problems such as skin disorders, fungal nail bed infections or angular cheilitis (cracking at the corner of the mouth). Recurrent upper respiratory tract infections (coughs, colds, sore throats, earaches, sinus problems) also indicate lowered immunity. Moderate weight loss (less than 10% of total body weight) may also be suggestive of HIV infection. People affected by these symptoms are unlikely to be prevented from going about their daily lives for very long by any health problem (they are fully ambulatory ).

14 medical monitoring: clincial monitoring and laboratory tests: 14 Slide 9 WHO staging system clinical stage three Chronic diarrhoea >1 month Severe bacterial infections Oral candidiasis stage three Prolonged fever >1 month (constant or intermittent) Vulvovaginal candidiasis Unintentional weight loss >10% body weight Oral hairy leukoplakia Pulmonary tuberculosis within the previous year Performance Stage 3: In bed more than normal but <50% of normal daytime during the previous month. clinical monitoring and laboratory tests: 9 WHO staging system clinical stage three At this stage, people with HIV infection have substantial immune system damage might be expected to develop some or all of these symptoms: Oral thrush Vaginal thrush Chronic diarrhoea that has lasted at least one month Serious bacterial infections of the lungs, infections of wounds that will not go away without antibiotic treatment TB White furry patches on the side of the tongue (oral hairy leucoplakia) A feverish state for much of the time in the past month Weight loss of at least 10% of the body weight At this stage, people with HIV infection are likely to be spending much more time in bed than usual, but will be able to go about their normal lives for at least half the days in the previous month.

15 medical monitoring: clincial monitoring and laboratory tests: 15 Slide 10 WHO staging system clinical stage four Kaposi s Sarcoma Progressive multifocal leukoencephalopathy Pneumocystis carinii pneumonia Cytomegalovirus disease of an organ other than liver, spleen or lymph node HIV encephalopathy HIV wasting syndrome Cryptococcosis, extrapulmonary Non-typhoid Salmonella septicemia Cryptosporidiosis with diarrhea >1 month Toxoplasmosis of the brain Atypical mycobacteriosis, disseminated stage four Herpes simplex virus infection, mucocutaneous Extrapulmonary tuberculosis Candidiasis of the oesophagus, trachea, bronchi, or lung Performance Stage 4: in bed >50% of normal daytime during previous month. Isosporiasis with diarrhea >1 month Any disseminated endemic mycois (for example, histoplasmosis) clinical monitoring and laboratory tests: 10 WHO staging system clinical stage four At this stage people with HIV will have developed serious illnesses which are life-threatening. See slide for details of these infections. Details of how to recognise and treat these infections can be found in a related module Treatment of opportunistic infections. They are likely to have spent more than half of the days in the previous month in bed and are increasingly unable to go about their normal lives.

16 medical monitoring: clincial monitoring and laboratory tests: 16 Slide 11 Exercise: the HIV disease course Draw diagonal line from bottom left to top right and label bottom left HIV infection and top right end of life Write in where you think symptoms will occur clinical monitoring and laboratory tests: 11 Exercise: the HIV disease course Objective: To identify the chronology of symptoms during the course of HIV disease Time: 15 minutes in one group Equipment: Blackboard or white board Task: The trainer draws a diagonal line from the left hand bottom corner of the board to the top right hand corner. The bottom of the line is titled `Becoming infected` and the top of the line `End of life`. The trainer asks the group to name symptoms that are seen in people with HIV, and to decide where the symptoms should be placed on the line. Divide the symptoms into stage 1, stage 2, stage 3 and stage 4. See example diagram below for a guide on where to place symptoms if there is any disagreement among group members Feedback Ask the group to explore any disagreements about where symptoms should be placed. Review the WHO clinical staging with the group again if necessary. Why is it important to know where symptoms appear along this line? Because it will help in identifying people who should be prioritised for treatment Because it will help in counselling patients about the value of HIV testing Where on the line do guidelines say that treatment is recommended? Why do you think this is so? Because all the symptoms beyond this point on the line are life-threatening and/or cannot be treated easily with available medicines

17 medical monitoring: clincial monitoring and laboratory tests: 17 Slide 12 Exercise: recognising symptoms of HIV disease Draw a picture of the human body and show which symptoms of HIV disease you might see in different parts of the body clinical monitoring and laboratory tests: 12 Exercise: recognising symptoms of HIV disease Objectives To familiarise participants with the range of symptoms that indicate advanced HIV disease, and to address any misunderstandings about possible symptoms To highlight which symptoms of HIV disease could be mistaken for other diseases To allow participants to share their observations about the range of symptoms seen in their clinical practice Time 15 minutes for small group work and 20 minutes for whole group discussion Equipment Large sheets of paper, whiteboard or blackboard for participants to draw on Task Draw people and show which symptoms you should look for in each part of the body to tell if a person has HIV disease OR Assign a different part of the body to each group and ask the groups to identify the symptoms that might appear in that part of the body

18 medical monitoring: clincial monitoring and laboratory tests: 18 Feedback Each group should choose a speaker to present their `symptom map` Key points Where differential diagnosis is difficult in untested patients, an HIV test is strongly recommended Encourage participants to talk about their difficulties in identifying HIV symptoms, and ask the group to discuss how they would solve the problem Refer to the diagram

19 medical monitoring: clincial monitoring and laboratory tests: 19 Slide 13 HIV antibody testing Two tests of different types should be carried out, one rapid test and one ELISA to confirm the rapid test OR 2 ELISA test OR 1 ELISA plus low CD4 count OR 1 ELISA plus AIDS defining illness Advantage of rapid test: people can be given results quickly too many people do not return Disadvantage: must be confirmed, slightly higher false positive rate clinical monitoring and laboratory tests: 13 HIV antibody testing The most basic requirement for starting HIV treatment is a confirmed HIV diagnosis. Diagnosis is usually confirmed by using antibody tests for HIV-1 and HIV-2 (most tests currently provide both of these). Two tests are needed, one to screen and one to confirm diagnosis. These may be an ELISA laboratory test (enzyme-linked immunosorbent assay), or a rapid HIV antibody test in a simple kit that can be used without laboratory facilities. Rapid tests are easy to perform on site and results are available within less than an hour. ELISA test results are not available so quickly and a patient may have to wait several hours or days to find out the result. Experience in many settings has been that patients often fail to return for ELISA laboratory test results. Rapid tests are therefore preferable in many settings even though they are more expensive, per test, than laboratory-based tests. They ensure that patients know their diagnosis and can receive advice on prevention, and access to treatment and support. However, rapid tests may yield a slightly higher false positive rate. Confirmatory tests should be done whenever possible in case of errors or false positive results from the first test. Although Western Blot tests are used for this purpose in well-resourced settings, they are too expensive to use where infection rates are high and resources are limited. An acceptable diagnosis of HIV can be based on two positive ELISA tests, one positive rapid test plus one positive ELISA test, one positive ELISA and a low CD4 count or one positive ELISA and any AIDS-defining condition. If only one test is possible, clear signs of immune deficiency (such as opportunistic infections) can confirm the diagnosis.

20 medical monitoring: clincial monitoring and laboratory tests: 20 Slide 14 HIV diagnosis in children Mother s HIV antibodies may persist in child until 18 months of age Viral load test, if available, will identify infection in newborns Alternative: p24 antigen test, looking for viral protein, can confirm, but negative test does not rule out HIV infection If unavailable: use mother s HIV status plus clinical symptoms and immune status clinical monitoring and laboratory tests: 14 HIV diagnosis in children If the mother is infected, a newborn baby will receive HIV antibodies from her, whether or not the baby itself is infected. Antibody testing is therefore unreliable in newborn infants. The mother s antibodies can persist for 12 to 18 months, after which an antibody test can be used for the baby. Tests such as PCR (Polymerase Chain Reaction) can detect the presence of HIV viral genetic material in a newborn baby, but it is costly and difficult to provide on a large scale. In the absence of definitive diagnosis, it is still possible to base treatment decisions on the mother s antibody status, combined with information on the CD4/CD8 ratio in the baby s blood and clinical examination of the baby. A cheaper and more practical alternative to PCR is a p24 antigen test. This test can be done in a small laboratory space, using equipment which is easily maintained without specialist technicians. p24 is the main HIV core protein, made by infected cells in larger quantities than other HIV proteins and therefore the easiest to detect. However HIV antibodies can mask the p24 protein and make it harder to detect. Detecting the presence of p24 in the baby s blood confirms HIV infection, but a negative result does not exclude it. It is possible to separate the p24 from any antibodies but tests for this are not yet proven to be appropriate for the subtypes of HIV that are clinically important in most parts of Africa and some other high-prevalence countries.

21 medical monitoring: clincial monitoring and laboratory tests: 21 Slide 15 Monitoring before treatment: protecting against side effects ESSENTIAL TESTS Haemoglobin (using visual scale if necessary) if AZT is included in available regimens Clinical exam for peripheral neuropathy NON-ESSENTIAL BUT DESIRABLE Liver enzymes Neutropenia (low neutrophil count) WHY NEEDED Zidovudine can make anaemia worse Stavudine can make peripheral neuropathy worse The combination of stavudine and didanosine can make peripheral neuropathy worse WHY NEEDED Nevirapine can cause liver enzyme increases; risk highest in those with high baseline levels Zidovudine can make neutropenia worse Pregnancy test if efavirenz is prescribed to women Efavirenz can harm the unborn child clinical monitoring and laboratory tests: 15 Monitoring before treatment: protecting against side effects ESSENTIAL TESTS WHY NEEDED Haemoglobin (using visual scale if necessary) if AZT is included in available regimens Zidovudine can make anaemia worse Clinical exam for peripheral neuropathy Stavudine can make peripheral neuropathy worse The combination of stavudine and didanosine can make peripheral neuropathy worse NON-ESSENTIAL BUT DESIRABLE WHY NEEDED Liver enzymes Nevirapine can cause liver enzyme increases; risk highest in those with high baseline levels Neutropenia (low neutrophil count) Zidovudine can make neutropenia worse Pregnancy test if efavirenz is prescribed to women Efavirenz can harm the unborn child

22 medical monitoring: clincial monitoring and laboratory tests: 22 Desirable tests: which are not absolutely essential but can provide significant information that would be helpful in monitoring of ART in resource-limited settings. These tests include CD4 cell counts, which are the best indicator of immunologic response to treatment and need to be much more widely available and tests for bilirubin, amylase, and serum lipids, which are used to assess the risk or development of some potential side effects of ART Optional tests: WHO currently considers viral load testing as optional in resource limited settings because of cost constraints; where resources permit, regular viral load monitoring is a direct measure of the effectiveness of ART in reducing levels of virus in a patient s blood. NOTE: The above text is excerpted from the WHO s Executive Summary, which can be accessed as an executive summary or in its entirety online at

23 medical monitoring: clincial monitoring and laboratory tests: 23 Slide 16 Exercise: why are we monitoring patients and what monitoring can we do? Why is it necessary to carry out monitoring tests? What tests do we need to do in order to ensure that as many people as possible are treated safely and effectively? clinical monitoring and laboratory tests: 16 Exercise: why are we monitoring patients and what monitoring can we do? Note: this exercise may not be appropriate where local monitoring only involves clinical assessment and where laboratory facilities are not available. Objectives To help the group to understand why monitoring is necessary, and what is recommended. To help the group understand the WHO clinical staging and how this relates to the need for treatment Equipment Paper for groups to write on Trainer actions: Check details of local monitoring protocols before the training session. Divide participants into smaller groups and ask them to spend minutes discussing the questions below. Then spend minutes feeding back to the larger group, and assemble a list of tests and reasons for doing them. Why is it necessary to carry out monitoring tests? What tests do we need to do in order to ensure that as many people as possible are treated safely and effectively?

24 medical monitoring: clincial monitoring and laboratory tests: 24 Feedback Why do we carry out monitoring tests? To check if patients need treatment To check if they have underlying conditions that might cause a bad response to treatment To check if the drugs we are giving will be suitable for the patient Why are these tests being used? Because of the drugs being used locally (eg AZT, stavudine nevirapine, efavirenz) Because it is possible to do these tests locally

25 medical monitoring: clincial monitoring and laboratory tests: 25 Slide 17 First clinical assessment of HIV-positive patient (1) Physical examination Weight Skin Lymph nodes Mouth (for signs of thrush, other lesions) Chest Pregnancy test Cough, fever? CD4 cell count if available Conduct these checks at each visit, and check reason for any missed appointments clinical monitoring and laboratory tests: 17 First clinical assessment of HIV-positive patient As mentioned above, as soon as a person is diagnosed HIV positive, he or she should receive a basic clinical assessment. The patient s medical history should be carefully documented with special attention to HIV-related symptoms with prognostic significance, past sexually transmitted infections, drug allergies and other medical problems. The assessment should include a thorough physical examination with close attention to weight, temperature, skin, respiratory tract, and lymph nodes. At subsequent clinical visits, continued monitoring of symptoms (such as coughs or sweats) and physical changes (such as body weight, skin, or lymph node size, for example) can indicate changes in immune status. It is also very important to be sure that there is no undetected serious illness, in addition to HIV, which could be treated or which might influence the choice of treatments that should be offered later. Physical examination Weight follow the weight over time to observe if the patient is losing weight. The first measurement is the baseline; if there is no clear evidence of wasting at the first visit, loss of more than 10% of body weight over subsequent visits is a clear indication of the progression of HIV disease (unless explained by severe food shortage) (WHO stage 3). Skin and nails rashes, boils and infections of the hair follicles (Folicultis) are signs of immune system damage due to HIV. Fungal infections of the nails, leading to discoloured toe nails, are also a sign of immune damage (WHO stage 2). More severe bacterial skin infections may be a sign that the patient has reached WHO stage 3. Lymph nodes swollen lymph nodes may be felt in the neck, under the arms and in the groin. Swollen lymph nodes may develop soon after infection (but note that in advanced disease severely swollen lymph nodes may also indicate TB or non-hodgkins lymphoma.

26 medical monitoring: clincial monitoring and laboratory tests: 26 Mouth (for signs of thrush, other lesions) oral thrush (usually visible on tongue or roof of mouth, accompanied by pain eating or swallowing) is a WHO stage 3 sign of immune damage. White ridges or patches on the side of the tongue without pain are likely to be oral hairy leucoplakia, a WHO stage 2 sign of immune damage. Oral warts are another early sign of immune damage. Severe cold sores/herpes lesions are also a sign of immune damage if they accompany other possible stage 3 symptoms they add to the probability that the patient has serious immune damage. Chest frequent and severe bacterial infections are a sign of WHO stage 3 immune damage. Evidence of TB on a chest X-ray qualifies as a WHO stage 3 diagnosing illness. Pregnancy test if pregnant, a woman with HIV should be referred for antenatal care that will include short course ARV treatment that will reduce the risk of transmission from mother to child. Cough, fever? this may indicate TB check other symptoms and refer for chest X-ray where suspected. CD4 cell count if available. Conduct all these checks at each visit, and check the reason for any missed appointments

27 medical monitoring: clincial monitoring and laboratory tests: 27 Slide 18 Screening for sexually transmitted infections Syndromic management start with signs and symptoms Syphilis Herpes PAP smear for cervical cancer if available STIs are often mixed, requiring syndromic management clinical monitoring and laboratory tests: 18 Screening for sexually transmitted infections At the initial clinical visit, doctors should screen for possible co-infections with common sexually transmitted infections (STIs). There is high incidence of acute STIs in many countries and the risk of HIV transmission is increased by both ulcerative and non-ulcerative STIs. Patients often have mixed infections and they can be difficult to diagnose by clinical examination alone. In resource-limited settings, laboratory tests may not be possible due to cost and time constraints, and patients often do not return to get their laboratory results. WHO therefore recommends the approach referred to as Syndromic Management of STIs, details of which are given in Guidelines for the Management of Sexually Transmitted Infections, which can be obtained from WHO or viewed at Syndromic management starts with observation of clinical symptoms and signs (syndromes) such as urethral discharge or genital ulcers and uses a flowchart (algorithm) to guide decisions about management and treatment. This approach has made adequate treatment of large numbers of infected people possible and cost-effective. Where laboratory facilities are available, diagnosis and monitoring can be supplemented with tests. Syphilis is a very common co-infection in people with HIV and all patients with suspected or confirmed syphilis should be strongly encouraged to have an HIV test. Syphilis can be screened for with a laboratory serological test, but a positive result might indicate a previous infection rather than a current one. Women who are HIV positive should, when laboratory and clinical facilities allow, have regular cervical (Pap) smears to check for potential cancer due to human papillomavirus (HPV)

28 medical monitoring: clincial monitoring and laboratory tests: 28 Slide 19 Screening for TB (1) Tuberculosis Sputum samples for active TB if cough or fever for more than 2-3 weeks If two out of three samples positive for TB, treat If one out of three: take more samples If all negative: treat as other chest infection and re-test if cough does not improve Chest x-ray if negative smears in presence of cough or fever clinical monitoring and laboratory tests: 19 Screening for TB Tuberculosis screening is vital to identify people who can benefit from curative or preventive treatment for TB. It is also necessary to make sure that people are receive the right type of treatment. A patient with active TB needs a full multi-drug course of active treatment, but a person with symptomatic HIV will need a course of preventive (prophylactic) treatment with one drug. If active TB is treated with only one drug, this can generate drug-resistant TB bacteria and is likely to be ineffective. If TB treatment is needed, this will influence the choice of ARV medications. WHO recommends that people receiving treatment for active TB should receive abacavir or efavirenz-based drug combinations in preference to nevirapine if ARVs must be taken alongside TB drugs. However, it is preferable to treat TB with four drugs for two months before starting ARVs unless the patient has a CD4 count below 50. Patients should be screened for active pulmonary TB if they have persistent cough (for more than 2-3 weeks) or fever, and weight loss. Three sputum specimens are collected at different times of the day. They are checked in a laboratory using a microscope and Ziehl-Neelsen or auramine stains and decisions made as follows:

29 medical monitoring: clincial monitoring and laboratory tests: 29 Slide 20 Screening for TB (2) PPD test for latent TB if no symptoms in any HIV+ patient PPD may be non-reactive in advanced HIV patients 6 month course of isoniazid may be advisable for ALL HIV+ patients clinical monitoring and laboratory tests: 20 Screening for TB If two of the specimens are positive for acid-fast bacilli (AFB), treatment can be started. If only one is positive, another set of three must be tested. If all specimens are negative, the patient may be prescribed a course of antibiotics in case of a different chest infection, and then three sputum samples are checked again. If symptoms persist but tests are still negative, the patient is referred for chest X-rays which can be helpful, but sometimes these might look normal even when there is active TB. Culturing tuberculosis can confirm diagnosis, but this takes up to 6 weeks and requires special facilities that might not be available. Extra-pulmonary TB affects other organs in the body and is less common than pulmonary TB, although it occurs more often in people with HIV. Microscopy of fluid or tissue taken from suspected TB lesions in other parts of the body can help in diagnosis of extra-pulmonary TB, along with clinical examination, especially for cervical lymphadenopathy, miliary (generalised) TB, meningitis, and effusions causing pleurisy, pericarditis and peritonitis. Many HIV-infected TB patients have both pulmonary and extra-pulmonary TB. The WHO recommends that experienced clinicians should treat suspected TB, even if it is repeatedly smearnegative, when there are X-ray abnormalities consistent with TB and the patient s symptoms have failed to respond to a course of broad spectrum antibiotics.

30 medical monitoring: clincial monitoring and laboratory tests: 30 People with HIV should be tested for latent TB, as well as being screened for active TB. A PPD skin test is used to test for previous infection. If the result is positive, a course of isoniazid preventive treatment (IPT) is recommended for six months to prevent progression to active TB. This is especially important for patients who are starting ART, because TB might become active during the early stage of immune system recovery (immune reconstitution). However, patients with damaged immune systems might not respond to a PPD test and PPD may not in any case be routinely available in some settings. WHO therefore recommends that IPT should be considered for anyone with HIV, such as health care workers, household contacts of TB patients, prisoners, miners, who is at risk of acquiring or transmitting TB, especially in high prevalence areas.

31 medical monitoring: clincial monitoring and laboratory tests: 31 Slide 21 First clinical assessment of HIV-positive patient (2) What is the home environment? Are there social structures or family members to support them emotionally and in practical ways? Who can the patient tell about their HIV diagnosis? Support from at least one family member is likely to improve a person s ability to take medication correctly. Is the patient employed? What is the patient s financial situation and will he or she be able to afford the costs associated with diagnosis and treatment (including transport, time away from work, child care etc.)? Does the patient face any particular problems because of gender, social position, sexual behaviour, injecting drug use, stigma or discrimination? clinical monitoring and laboratory tests: 21 First clinical assessment of HIV-positive patient Information should also be recorded about the patient s lifestyle and social background because these might affect his or her ability to access or make use of treatment. For example: What is the home environment? Are there social structures or family members to support them emotionally and in practical ways? Who can the patient tell about their HIV diagnosis? Support from at least one family member is likely to improve a person s ability to take medication correctly. Is the patient employed? What is the patient s financial situation and will he or she be able to afford the costs associated with diagnosis and treatment (including transport, time away from work, child care etc.)? Does the patient face any particular problems because of gender, social position, sexual behaviour, injecting drug use, stigma or discrimination?

32 medical monitoring: clincial monitoring and laboratory tests: 32 Slide 22 Exercise: First clinical assessment of HIV-positive patient (3) Who should be involved in the first assessment of the patient? Why? Draw a map of all the factors that could affect the patient s ability to take treatment correctly clinical monitoring and laboratory tests: 22 Exercise: first clincial assessment of HIV-positive patient Objectives To help health care workers consider the full range of factors influencing a person s ability to take medication, and the community support available to promote good adherence to treatment. To encourage health care workers to consider how the assessment of patients can be managed and improved within available resources To encourage an understanding of the link between monitoring (a clinical activity) and preparing patients for treatment (a form of care involving a wider circle of people) Time 30 minutes in small groups and 30 minutes feedback/discussion as a whole group Trainer actions Write the questions below on a board or display in the training room throughout the exercise period. Divide the group into smaller groups (ideally no more than 8 in one group to allow everyone the chance to contribute). Point out that the list of factors will be used in a linked exercise, in which the group will consider solutions to help people take treatment. Equipment Paper for each group to write a list of key points

33 medical monitoring: clincial monitoring and laboratory tests: 33 Task Who should be involved in the first assessment of the patient? Why? Draw a map of all the factors that could affect the patient s ability to take treatment correctly Feedback Ask each group to choose a speaker who will explain the group s map, and who they think should be involved in the assessment of the patient. Draw up a list of points of agreement between each group s presentation, and explore any differences which arise. Try to establish a group consensus on the most important factors affecting the patient s ability to take treatment. Points to consider This exercise assumes that the majority of people diagnosed with HIV during the early stages of a treatment programme will be eligible for treatment, or will soon need treatment. Will all patients need treatment immediately? How will the need for treatment or the need to wait for treatment be explained to patients? Does the patient have TB? If so, this will influence the choice of ARV medication that can be prescribed (assuming there are alternatives). The patient will also require TB treatment. For some patients, it may be necessary or advisable to carry out TB treatment first and then start ARVs later. Does the doctor have time to find out all the information about a patient? Will the patient tell the doctor everything that might affect their ability to take medication? Why not? Who can the patient tell about their HIV diagnosis? How can they be helped to disclose to a supportive family member? What is the home environment? Are there social structures or family members to support them emotionally and in practical ways? Is the patient employed? What is the patient s financial situation and will he or she be able to afford any costs associated with diagnosis and treatment (including transport, time away from work, child care etc.)? How will their job affect their ability to take medication at the right times? Does the patient face any particular problems because of gender, social position, sexual behaviour, injecting drug use, stigma or discrimination?