1 Unit 5: IPT Isoniazid TB Preventive Therapy Botswana National Tuberculosis Programme Manual Training for Medical Officers
2 Objectives At the end of this unit, participants will be able to: Describe the role of INH Preventive Therapy (IPT) for HIV-infected persons with latent TB infectionDescribe how to appropriately screen eligible patients for IPT
3 IPT: Isoniazid Preventive Therapy Type of secondary preventionTo prevent development of active TB in HIV positive individuals in whom active TB has been excluded6-month course of INHINH= Isoniazid, IPT= Isoniazid Preventive TherapyThe purpose of IPT is to prevent TB infection from progressing to TB disease (reactivation), and it is therefore a form of secondary prevention in the BNTP’s recommended use in HIV positive individualsNote that the protective efficacy of IPT in people with ”latent” TB infection is about 90% among people who are HIV- and 60% among HIV+ individualsThe duration of prevention may be limited. Botswana is currently conducting a three-year trial to determine how long protection lasts as a proxy for life-long treatmentSee Section 3.2 in Botswana National Tuberculosis Programme Manual
4 Rationale for IPT10% lifetime risk of developing active TB if infected with M. tuberculosis alone5-10% annual risk of developing active TB if co-infected with HIVIPT is meant to prevent progression of latent TB to active diseaseINH shown to decrease incidence of TB among HIV- infected persons by about 40%The protection period ranges from <1 year to 3 years**Studies conducted in several African countriesSource: Republic of Botswana Ministry of Health. National Tuberculosis Programme Manual. 2007; Sixth Edition.Discuss reinfection because it lowers the effectiveness of IPT. This is not due to the effectiveness of the drug, rather because once the treatment ended, people were exposed to other TB cases and reinfectedSource: BNTP Manual, 2007.
5 Rationale for IPT in Botswana HIV prevalence is 17.1% in general population*TB case rate increased ~ 3-fold in 1990s**1989: 199 /100,0002002: 623 /100,000~80% of adult TB cases are HIV co-infected***Patients more likely to seek HIV testing if they would receive health benefit such as IPT and ART (1999 KABP study in Botswana)TB is the leading killer of persons with AIDS in BotswanaThese numbers are showing the need for IPTAll districts in Botswana offer IPT to HIV positive individualsWith the help of the IPT strategy, it is hoped that the burden of TB among PLWHA will be reducedRecent survey from Botswana indicates 84% co-infection with TB/HIV*Source: Botswana AIDS Impact Survey-II: Preliminary Results. The Republic of Botswana, Central Statistics Office [press release 2004 Dec 16]. Available from:** Source: BNTP Manual, 2007.***Source: HIV Medicine Association, Infectious Diseases Society of America, The Forum for Collaborative HIV Research. HIV/TB Coinfection: Basic Facts [fact sheet] Oct.Sources: *HIV Medicine Association, et al., 2007** BNTP Manual, 2007.***BIASII, 2004
6 IPT Effectiveness South African Miners, 2003 IPT usage TB incidence IPT (n=338)8.6/100 person yearsNo IPT (n=221)19.1/100 person yearsINH was given for 6 months to one of two cohorts of South African minersThe cohort that received no INH had a TB incidence of 19.1 cases per 100 person yearsThe cohort that received INH had a incidence of 8.6 person years, a 55% reductionSource: Churchyard GJ, Fielding K, et al. Efficacy of secondary isoniazid preventive therapy among HIV-infected Southern Africans: time to change policy. AIDS Sep 26; 17(14):Source: Churchyard GJ, Fielding K, et al., Aurum Health Research, 2003.Overall 55% reduction in TB incidence
7 IPT Effectiveness Related to ART TB Incidence in 11,026 HIV-infected patients in BrazilNo INHYes INHNo ART4.01/100 person years1.27/100person yearsYes ART1.90/100 person years0.80/100INH alone cut TB incidence dramatically, but there was additional benefit from ARTSource: Golub JE, Sraceni V, Cavalcante SC, et al. The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosis incidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS Jul 11; 21(11): Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, USA.Source: Golub JE, et al., Johns Hopkins University 2007.76% reduction with both INH and ART when adjusted for age, previous TB diagnosis and CD4 count at baseline
8 Assessment for IPT Medical and social history TB Screening questions Previous exposure to TBPrevious treatment for TBHIV positiveTB Screening questionsPhysical examinationClinical evaluation of TB suspectsSputum smear for microscopy and other investigations as indicatedThis is the screening algorithm which is the tool most used to determine eligibility to begin IPTNote: a screening chest radiograph is not necessaryEligibility to enroll on IPTConfirmed HIV infectionExclusion of active tuberculosis to avoid monotherapy, which could lead to the development of INH resistanceNot currently pregnantNo terminal AIDSNo history of hepatitis and no active hepatitis at enrolmentNo prior history of isoniazid intoleranceNo history of TB in the previous 3 yearsNot a habitual treatment defaulter
9 Screening Questions Cough for 2-3 weeks Weight loss Night sweats Fever MalaiseShortness of breathChest painHaemoptysisConsider EPTB:LymphadenopathyHeadacheAbdominal pain or distensionSwollen jointsBackache
10 Patients with Advanced HIV Disease TB Screening Tests inPatients with Advanced HIV DiseaseThis table shows the specificity and sensitivity of a number of screening tests for tuberculosis in patients with advanced HIV diseaseActive TB was found in 8.5% of advanced HIV patientsA simple screening instrument, the sputum culture, had a sensitivity of 90.9% and a specificity of 100%.Source: Mohammed A, Ehrlich R, Wood R, Cilliers F, Maartens G. Screening for tuberculosis in adults with advanced HIV infection prior to preventive therapy. Int J Tuberc Lung Dis. 2004; 8(6): IUATLDMohammed A, et al. Int J Tuberc Lung Dis, 2004.
11 Screening Algorithm for IPT Signs / symptoms of PTBYESNOINITIATE IPTSputum microscopy x 3 for AFBTREAT FOR TBCXR & assessmentTreat for bacterial infectionGood responsePoor responseAll negativeONE positiveTB unlikelyTB likelyThis algorithm has been adapted from the BNTP manualRefer to Handout 5.1
13 Preventing Isoniazid Resistant TB Constant & proper use of the algorithm for the dx of PTB to prevent monotherapyScreening of patients at each visitThorough investigation of those suspected of having TBOngoing counselling of patients to maintain adherenceMono-therapy refers to undiagnosed active TB patients inadvertently placed on IPT because of improper/inadequate screeningDon’t overlook the possibility of (extrapulmonary) TB in patients just because they are not coughing. Consider the results of the entire screening tool and, before starting IPT, pursue additional evaluation in any patient who is not in their baseline health.Refer to the screening algorithm on Handout 5.1 in the Participant Handbook
14 Emergence of Resistance with Single Drug Therapy of Active TB Start INH aloneLegend:Red Line: INH-Sensitive TB organismsBlue Line: INH-Resistant TB organismsIf active TB is treated with only INH, initially the majority of TB organisms will be sensitive to it (although 1 out of 10 million will be naturally resistant to INH)During single-drug treatment with INH, the organisms SENSITIVE to INH will die, but those naturally resistant will continue to multiply, and eventually will be larger in # than those sensitive to INH. This is seen between weeks 8 & 10 of therapy in the graph above – where the two lines of sensitive and resistant cross overBy week 24 there are very few INH-sensitive organisms left and many INH-resistant organismsEssentially, M. tuberculosis bacteria become resistant to INH meaning that the drug is not longer active in killing the organism
15 Reasons to Stop IPTPatient misses 2 consecutive monthly refill/monitoring appointmentsDevelops INH intolerance (serious side effect)Becomes terminally illPotentially stop if female patient becomes pregnantIf less than 3 months of IPT, discontinueIf more than 3 months of IPT, continue treatmentDevelop symptoms of active TBINH intolerance:JaundiceSevere allergySevere skin rashNote: Jaundice is a rather late sign of drug induced liver injury; ideally therapy could be interrupted in the pre-icteric phase where the risk of progression to fulminant hepatic necrosis is much lower. If resources and education permit, I would suggest advising patients to hold INH and seek evaluation if anorexia/nausea/fatigue lasts greater than 5 days. Depending on resources, either an ALT or AST could be checked (or at least a clinical evaluation be performed) before resuming treatment.
16 Patient Education Point Ensure HIV positive patients understand the benefits of IPT (55% reduction in TB disease)Reinforce information at each visitAssess adherence to therapy, as with TB treatmentPatients should be taught to recognize signs & symptoms of active TBDiscuss side-effects and support patient by problem solving ways to manage minor SEsEncourage questionsUnit 5: Infection Control and Prevention of TB
17 Key PointsIt is important to appropriately screen for signs & symptoms of TB in HIV positive individuals before initiating IPTHIV positive individuals have a 5-10% chance of developing active TB per yearIPT can prevent TB disease in HIV positive individuals