Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Introduction • TB is the leading cause of death among PLHIV • Isoniazid Preventive Therapy (IPT) is used to prevent TB among PLHIV who do not have TB disease and meet eligibility criteria for IPT • IPT is one of the 3 I’s strategies to reduce the burden of TB among PLHIV Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 2 Learning Objectives • By the end of the session, participants should be able to: • • • • • Explain the rationale for IPT Determine which patients are eligible for IPT Explain and prepare patients for IPT Describe how to start and monitor IPT Manage common side effects associated with IPT Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 3 Rationale for IPT (1) • Aim of introducing IPT to PLHIV is to prevent active TB in patients who do not have it • WHO/UNAIDS recommends use of IPT for PLHIV in areas where co-infection is > 5% • An estimated 10-15% of PLHIV have active TB disease • Over 30% of AIDS-related deaths among adults are due to Tuberculosis Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 4 Rationale for IPT (2) • MOHSW Policy statement for IPT • Health facilities (H/F) with sufficient capacity will be accredited to offer IPT in strict compliance with national and international guidelines • INH will be provided to eligible patients free of charge in accredited H/F • MOHSW will: • develop a procurement and logistical management plan for sustainable provision and supply of INH at service delivery points • be the accrediting body and regularly monitor and evaluate IPT use in the country Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 5 Purpose of Using IPT • IPT is aimed at decreasing the risk of a first or recurrent episode of TB • Among PLHIV, IPT is likely to provide protection against the risk of developing TB by decreasing the risks of: • Progression of recent infection • Reactivation of latent M. Tuberculosis • IPT programs decrease rate of TB in the community and improve TB control Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 6 Role of IPT in Preventing TB Disease Early progression (5%) IPT Infection (30%) Inadequate Immunological Defenses Late progression(5%) Inadequate IPT Immunologic Defenses Adequate I.C. Adapted from Phil Hopewell Containment (95%) Adequate Exposure Session 6 Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Continued containment (90%)7 How Long Does IPT Work? • The IPT prevention effect against TB lasts for 1–2 years after the 6-9 month course and then the risk of TB gradually returns because of new exposures • After 1-2 years, re-infection may occur and secondary IPT is recommended Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 8 PLHIV Eligible for IPT Who Should Receive IPT in Tanzania? • People at high risk for TB such as: • HIV exposed and unexposed infants of mothers with pulmonary TB • All children <5 yrs in contact with smear positive TB patient • All persons who are HIV positive and in particular those who are: • • • • • Family members of a sputum smear positive TB patient Prisoners Hospitalized patients and outpatients Health care workers Individuals in congregate settings Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 10 IPT Exclusion Criteria (1) • Exclusion: • TB suspect / patient with confirmed active TB disease • Patient currently on TB treatment and those with history of completed TB treatment and/or IPT in the past 2 years* Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 11 IPT Exclusion Criteria (2) • Medical contraindications to INH* (current or prior) • Intolerance/allergy to INH • Chronic/acute liver disease • Alcohol abuse • Poor compliance / adherence • Terminal AIDS stage 4 (as per WHO palliative care definition) • Pregnant mothers Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 12 Inclusion Criteria for IPT • Those who are eligible for IPT: • Have been documented as HIV positive • Are fifteen years of age and above • Do not meet any of the exclusion criteria Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 13 Case Study 1: Assessing Eligibility for IPT • Malika is a 41 year old teacher who is referred to CTC after having been diagnosed HIV-positive at VCT. She is very woried about her health since she has two young children under 5 whose HIV status is unknown. She does not report signs and symptoms of tuberculosis • How would you assess this patient for TB? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 14 Case Study 1 (continued) Tick appropriate response Do you have the following: • Cough for ≥ 2 weeks? • Coughing up bloodstained sputum (haemoptysis)? • Fevers for ≥ 2 weeks? • Noticeable weight loss for new patients or a 3 kgs weight loss in a month (subsequent visit)? • Excessive sweating at night for ≥ 2 weeks? yes no □ √ □ √ □ √ □ √ □ √ ....... this patient is HIV-positive but she is apparently “healthy”! Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 15 Case Study 1 (continued) HIV-infected patient with ALL answers NO on the TB questionnaire No need to undertake AFB microscopy This patient is considered an asymptomatic PLHIV. Therefore: Assess for IPT eligibility Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 16 Case Study 2: Assessing Eligibility for IPT • Maisha is a 39 year old taxi driver from Kabwete and has been living with HIV for 3 years. On this visit to the Kabwete CTC he complains of fever and cough which have lasted for the past 3 weeks. Upon further questioning, he admits to having lost 3 kg in the last month. Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 17 Case Study 2 (continued) Tick appropriate response Do you have the following: • Cough for ≥ 2 weeks? • Coughing up bloodstained sputum (haemoptysis)? • Fevers for ≥ 2 weeks? • Noticeable weight loss for new patients or a 3 kgs weight loss in a month (subsequent visit)? • Excessive sweating at night for ≥ 2 weeks? yes √ □ √ no □ √ □ √ □ □ √ .....This patient has several signs/ symptoms that qualify him to be a “TB suspect” Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 18 Sputum Request Form MOHSW Tanzania • If you suspect TB in a patient, use the sputum request form to refer the patient to the lab for a sputum test Session 6 Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation 19 Case Study 3 • Fatim is a 34 year old police officer who has been attending another CTC but was recently transfered to the city. As a new patient to your clinic, you decide to assess her TB status. • How will you introduce the subject of TB screening? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 20 Case Study 3 (continued) • Upon further discussion with Fatim, you discover that she has had a fever for about 10 days. Her weight is 48 kg and she looks a little wasted. She knows that her weight was 55 kg 3 months ago. She denies having a cough but says she has chest pain. She has no memory of ever having had an opportunistic infection. Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 21 Case Study 3: What Are the Next Steps? • You discover the following additional information while you are discussing her case: • • • • Physical examination is negative Hb: 10.3 CD4: 180 (1 week ago) She is not on ART Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 22 TB Screening Questionnaire Tick appropriate response Do you have the following: Cough for ≥ 2 weeks? Coughing up bloodstained sputum (haemoptysis)? Fevers for ≥ 2 weeks? Noticeable weight loss for new patients or a 3 kgs weight loss in a month (subsequent visit)? Excessive sweating at night for ≥ 2 weeks? yes □ no √ □ □ √ □ √ □ √ √ Hmm!!! This patient has borderline symptoms Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 23 Case Study 3: Next Steps? • Does the patient have active TB? • Do you think it is relevant to investigate the patient’s and relatives’ history? • Findings: • • • • AFB microscopy test: negative (saliva seen) CXR: negative for active TB Patient does not report history of past TB The patient’s father who stays at her home is on TB treatment Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 24 Case Study 3: Conclusions • • • • • What is your conclusion? Does the patient have TB? If yes, would you start TB treatment? Otherwise, is the patient eligible for IPT? Do you suggest to conduct additional investigations? • How do you plan the follow-up? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 25 Before initiating preventive therapy, active TB must be excluded! • Due to the increased rate of smear negativity in HIV-infected individuals, a chest radiograph is necessary in addition to a negative sputum smear to exclude active TB with any certainty Session 6 Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation 26 Assessment of IPT Eligibility IPT Algorithm -1 Session 6 Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation 28 IPT Algorithm - 2 Session 6 Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Counselling 29 Preparation of the Patient for IPT Adherence Education and Counseling Flow Chart PLHIV is eligible to start IPT PLHIV is referred to Adherence Nurse Pre-IPT Adherence Counselling 1. 2. 3. 4. 5. 6. 7. 8. Assess patient’s knowledge of HIV and TB Recommend Treatment Assistant Educate patient about the relationship between HIV and TB Educate about importance of IPT Explain drug regimen, side effects and importance of adherence Identify barriers to adherence and strategies to overcome barriers Assess patient’s readiness to start IPT Document in Adherence checklist Source: SOP for HIV care and treatment – NACP MOHSW Tanzania Session 6 Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation 31 Prescribing IPT • Write down the dose and duration of INH • Dose: 300 mg daily • If patient weighs <30 kg: dose 5 mg/kg • Duration: 6 months • Pyridoxine • Dose: 25 mg daily • Duration: 6 months Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 32 What is Considered Good IPT Adherence? • An uptake of 80% or more of the total doses of IPT is enough to achieve the protective effect • At the end of 6 months, patient should have taken 180 pills (which =100%) • If patient has not taken at least 80% (144 doses), then needs to continue on IPT to complete the total within a maximum time of 9 months Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 33 Group Discussion: How Do You Assess Whether Your Patients Are Adherent? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 34 Follow Up Visits • Give dates for follow up appointments at monthly follow up (whether PLHIV on ART or in care) • At the follow up visit: • • • • Assess adherence Continue counselling/continuous education Assess for side effects Screen for development of active TB (even if patient is on IPT) • Check for signs and symptoms of TB • Use screening tool • Check drug supplies Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 35 Remember: It is Still Possible to Miss TB During IPT • In a study done in Tanzania, it was found that of the 93 patients studied, 14 (15%) had active TB of which: • 10 (71%) had clinical TB (symptoms or chest radiograph findings) • 4 (29%) had subclinical TB (positive sputum AFB stain or culture results but no symptoms or chest radiograph findings) Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 36 Assessing Adherence • • • • Patient self-report Detailed interview Pill counts Pharmacy refill data Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 37 Role Play Activity Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 38 Case Study: Adherence During IPT • 38 year old HIV-positive male at the end of the 2nd month of IPT travels to a relative’s funeral without informing the CTC staff. Before leaving, he takes the last 4 tablets of INH. One month later he comes back to the CTC reporting having missed doses for the past 4 weeks. • What action will you take? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 39 Other Challenges to IPT Implementation • For patients, the following may affect success of IPT programs: • Financial barriers affecting travel to collect drug supply leading to missed appointments • Secrecy and stigma with PLHIV who fear being seen collecting medications • Fears of being on the drug for a long time • Fear of side effects, based on experiences of peers • Inadequate access to food Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 40 Adherence Support Strategies for IPT Programmes Adherence Support • • • • • Patient education and counselling Access to uninterrupted medication supply Medication reminders Medication partners Ongoing support and reinforcement Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 42 Patient Education and Counselling • Patient education should take place prior to IPT initiation, but should also continue throughout the course of IPT use Remember, adherence may decrease over time Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 43 Ensuring Uninterrupted Supply of IPT • Ensure that patients understand where, when, and how to obtain medications • Avoid “stock outs” by accurately balancing needs and consumption • Assist patients to safeguard medicines • Provide access to care to patient’s household, limiting pressures to share medicines Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 44 IEC and Peer Educators • Educate patients and the public on TB • Use TB patients or those who have been on IPT to educate other patients • Use the support of peer educators to conduct counselling/education for PLHIV on IPT Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 45 Side Effects of INH Side Effects and Management Side Effect Mild -Tingling/ burning sensation - Joint pain - Mild skin rash -Abdominal pain Severe - Hepatitis/ jaundice - Severe skin rash with peeling skin - Disabling peripheral neuropathy - Convulsions Session 6 Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Management Continue with INH Reassure Reassess STOP INH Refer for further management 47 Concurrent Use of Herbs • There is potential for interaction between herbs and INH • Unless the components of the herbs are known, concomitant use should be discouraged Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 48 Case Studies on Side Effects Case Study 1 • 56 year old HIV-positive man started IPT 3 weeks ago - dose of 300 mg/day. He comes back to CTC complaining of itching skin lesions on upper body for 5 days • He has no other signs/symptoms • Clinical examination shows rash, no ulcers • Is this due to drug toxicity or another acute illness? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 50 Case Study 1 (Continued) • Upon taking additional history you discover that he has also taken traditional medicine to cure the rash, with no benefit. The patient is not taking any other drug and is not on ART. The patient has never reported any similar signs or symptoms before • Is this problem due to the traditional medicine? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 51 Case Study 2 • 28 year old HIV-positive Mariam was started on IPT 2 months ago at a dose of 300 mg/day. She is not taking Pyridoxine because it was out of stock at the pharmacy. She returns to CTC complaining of numbness of the toes. • What is your diagnosis? • What is the differential diagnosis? • What other questions would you ask? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 52 Case Study 2 (continued) • The patient is not diabetic, does not drink alcohol and eats well. No other drugs have been taken (the patient is not on ART; CD4=320) • Does the patient have peripheral neuropathy? Or is it something else? • Do you think it is caused by INH? • Is the time course consistent? • Should the IPT be stopped? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 53 Development of TB during IPT (1) • Although a small proportion of patients on IPT may develop active TB disease, there are public health consequences to this therefore it is important to keep reassessing for active TB at every visit • Remember to repeat TB screening questionnaire at every follow up visit! Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 54 Development of TB during IPT (2) Overall Guidance: 1) Stop IPT 2) Start anti-TB medication 3) Substitute NVP with EFV (if on NVP-containing ART regimen) Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 55 PLHIV on IPT Develops Active TB After Starting ART TB Type of TB occurrence Management of ART Within 6 months of starting ART Stop IPT. If already on EFV: continue If on NVP; substitute with EFV Start TB treatment Any After 6 months PTB or EPTB lymph of ART nodes of uncomplicated pleural TB without clinical and/or immunological evidence of disease progression EPTB other than types listed above Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Stop IPT. Continue ART regimen switching to EFV and re-assess the patient at completion of TB treatment If already on EFV: continue If on NVP; substitute with EFV Start TB treatment Stop IPT. Start TB treatment Consider as ART failure and switch to 2nd line regimen Slide 56 Use of INH and ART in PLHIV in Stages 3 and 4 (1) Logistics and advantages: • ART indicated in such patients • INH may be more useful for stage 3 or 4 patients (with no TB) • For those on ART, the regular follow-up for HIV C&T should also address adherence to INH Problems: • May be difficult to exclude TB in these patients, especially stage 3 disease • INH may add to toxicity of ARV drugs, especially Stavudine (d4T), Didanosine (ddI) • Extra pills to take and this may compromise adherence Consider drug-drug interactions BUT these Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation should not delay or interrupt IPT! Slide 57 Use of INH and ART in PLHIV in Stages 3 and 4 (2) • New symptoms in patients with advanced HIV who are on IPT and start ART may be due to: • • • • Immune reconstitution syndrome (IRIS) Active TB Other OIs Side effects of ART Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 58 Protocol for Managing IRIS • Investigate for OI and manage accordingly • Give adequate fluids, intravenously if possible • If available, offer NSAIDs for control of mildmoderate fever, inflammation, and pain • Do not stop IPT, unless IRIS is severe or TB is diagnosed • Do not stop ART, unless IRIS is severe • Add steroids if reaction is severe (according to national guidelines) • Counsel patient, caregiver and treatment assistant Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 59 Case Study 3 • 37 year old HIV-positive woman started 3TC + d4T + NVP six weeks ago. She is eligible for IPT and starts INH 300 mg/day • 10 days later she comes back to the CTC complaining of abdominal pain and tiredness. She is jaundiced and looks dehydrated. She has right upper quadrant tenderness on abdominal examination • What is the possible cause of these findings? Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 60 Nevirapine and Hepatotoxicity • In addition to rash (the most common side effect), NVP may cause hepatotoxicity which can, in rare cases, be severe Possible causes Side effect Hepatitis Anti-TB drugs ARV drugs PZA RIF INH NVP PI Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 61 Risk Factors for Developing Hepatotoxicity • Baseline elevation of AST or ALT • Chronic viral hepatitis (HBV, HCV) • Alcohol abuse Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 62 Normal Liver Enzymes Upper limit of normal (ULN) for ALT • Male 10-40 U/L • Female 7-35 U/L Upper limit of normal (ULN) for AST • Male 15-40 U/L • Female 13-35 U/L Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 63 Grading Hepatotoxicity For patients with normal pre-treatment AST and ALT • Grade 0: < 1.25 x upper limits of normal • Grade 1: 1.25-2.5 x upper limits of normal • Grade 2: 2.6-5 x upper limits of normal • Grade 3: 5.1-10 x upper limits of normal • Grade 4: > 10 x upper limits of normal AIDS Clinical Trial Group Scale Management of Hepatotoxicity depends on the grade Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 64 Case Study 3 (continued) • The following tests are then performed for this patient with the following results.... Lab Hb=11.2 ALT= 303, AST=405 Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 65 Hepatotoxicity Management • Grade 0-2: Continue ARVs and IPT, monitor closely • Grade 3-4: Discontinue ART and IPT • Stop all three antiretroviral drugs • Monitor closely (clinical and laboratory monitoring) • Wait until symptoms and laboratory abnormalities resolve • Start new ART regimen (without NVP) and restart INH Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 66 Management of Skin Rash (1) • If rash is mild: • Give antihistamine and continue with IPT • Monitor closely, do LFTs • Prednisolone 40mg/day may be given until rash clears • then taper dose gradually before complete stop Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation • If severe rash occurs: • STOP IPT immediately • START high dose steroid e.g. prednisolone 6080mg/day • if oral medication not possible, give IV dexamethasone or hydrocortisone Slide 67 Management of Skin Rash (2) • Give antihistamines • Manage other symptoms, e.g. pain, with analgesics • Admit patient to hospital for observation, or refer as needed • Consider IV fluids, especially if there is Stevens-Johnson Syndrome • Consider antibiotics e.g. cloxacillin if secondary bacterial infection is suspected • Monitor carefully and do LFTs Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 68 IPT in Pregnancy • Pregnancy is not a contraindication to IPT but should be deferred until the postpartum period • IPT can be started as soon as the first postpartum visit (6 weeks PP) • IPT is safe during lactation • Source: Snider; Francks 1988, Thompson Micromedex online Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 69 Key Points (1) • IPT is aimed at decreasing the risk of a first or recurrent episode of TB • IPT should only be prescribed when it is possible to rule out active TB • Consider other IPT exclusion criteria before initiation • Adherence is essential for IPT effectiveness • IPT side effects should be managed in order to improve adherence Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 70 Key Points (2) • Given that IPT could still cut number of active TB cases by 30 to 50%, a slight increase in resistance is still not a good excuse to prevent roll-out of IPT • However, it does suggest that more attention should be given to optimizing the screening process – to reduce the number of active TB cases that are missed – and to the management of people with breakthrough disease • When active TB occurs among those given IPT, the recommended initial treatment regimen for treatment remains RHZE Session 6: Isoniazid Preventive Therapy (IPT), Part I: Patient Eligibility and Preparation Slide 71