Elzi, Luigia

Furrer, Hansjakob

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1394 • CID 2007:44 (15 May) • CORRESPONDENCEern Reserve University Research Collaboration.N Engl J Med 1997; 337:801–8.3. Rose DN. Short-course prophylaxis against tu-berculosis in HIV-infected persons: a decisionand cost-effectiveness analysis. Ann Intern Med1998; 129:779–86.4. Chapman AL, Munkanta M, Wilkinson KA, etal. Rapid detection of active and latent tuber-culosis infection in HIV-positive individuals byenumeration of Mycobacterium tuberculosis-specific T cells. AIDS 2002; 16:2285–93.Reprints or correspondence: Dr. Frank A. Post, Academic Dept.of HIV/GU Medicine, Weston Education Centre, CutcombeRd., London SE5 9RJ, United Kingdom (frank.post@kcl.ac.uk).Clinical Infectious Diseases 2007; 44:1393-4 2007 by the Infectious Diseases Society of America. Allrights reserved. 1058-4838/2007/4410-0027$15.00DOI: 10.1086/518774Reply to Hamlyn et al.To the Editor—Hamlyn et al. [1] drawattention to the limited impact on theoverall number of prevented cases of tu-berculosis (TB) if a strategy of screeningand treatment of latent TB in HIV-in-fected patients would be routinely adoptedin a setting of low TB prevalence. Assum-ing a reduction in the number of TB casesof 56% by implementation and followingof a screening and preventive treatmentstrategy in HIV-infected patients, only 3TB cases per year would have been pre-vented in their hospital, where only 5% ofall TB cases occur among patients withpreviously diagnosed HIV infection.Their statement that, in our study, 142patients had TB before HIV diagnosis isnot entirely correct. These patients had TBbefore they gave consent to be observedin our cohort, but HIV infection may havebeen diagnosed earlier. The number of pa-tients who had TB before or at the timeof diagnosis of HIV infection was 65 [2].But Hamlyn et al. [1] are correct in point-ing out that TB diagnosis or clinical signsof TB are circumstances that lead to thesuspicion and diagnosis of HIV infectionin a considerable proportion of patientswho, therefore, are not eligible for tuber-culin skin tests (TSTs) and preventivetherapy. Only earlier detection of HIV in-fection could enable us to prevent TB ina proportion of this population.The concern of Hamlyn et al. [1] aboutthe efficiency of a strategy of TB preven-tion is in concordance with the editorialcommentary by Rieder [3] that accom-panied our article. A large part of thequestionable efficiency results from thedifficulties in implementing the TB-pre-vention strategy, as shown in our cohort,in which certain centers performed TSTsfor !40% of patients and in which only37% of patients with positive TST resultsreceived preventive therapy.Every treatment facility has to decidewhether implementing a TB-preventionstrategy makes sense in their setting. Ourdata suggest that preventive chemopro-phylaxis is efficacious and effective.Among the individuals with positive TSTresults, 15 have to be treated to prevent 1case of TB, and the corresponding numberto treat for patients who originate fromcountries where TB is highly endemic isestimated to be 8. Therefore, we decidedto enhance the means of detection andtreatment of latent TB in our cohort, be-cause we believe that this strategy is fea-sible in our setting.There are several reasons to justify suchan approach, even if the absolute numberof prevented cases seems to be modest.First, identification and treatment of in-dividuals at high risk of developing TB arecrucial public health issues and corner-stones of TB-control policies. Therefore,considering the absolute number of pre-vented diseases in a cohort study of HIV-individuals does not take into account thepotential number of prevented cases thatwould have been infected by those pa-tients. Second, at an individual level, treat-ment of active TB carries a higher risk ofnonadherence, adverse effects, and druginteractions with antiretrovirals than doespreventive treatment [4, 5]. In addition,the risk of immune reconstitution syn-drome in HIV-infected individuals afterreceipt of TB and antiretroviral treatmentmay lead to considerable morbidity andfavors TB-prevention strategies [6–8].Finally, we do not believe that IFN-grelease assays will accurately identify allHIV-infected patients with latent TB be-cause of the reduced sensitivity among im-munodeficient patients [9]. However, wecan expect a higher specificity, leading toa reduced number of patients in need ofpreventive therapy—especially amongpersons who have been vaccinated withbacille Calmette-Gue´rin [10].Therefore, we think that screening HIV-infected patients for latent TB with TSTsor, possibly, IFN-g release assays and treat-ing those patients with suspected latent TBis an advisable strategy to reduce TB-re-lated morbidity, even in the setting of alow TB prevalence.AcknowledgmentsPotential conflicts of interest. L.E. and H.F.:no conflicts.Luigia Elzi1 and Hansjakob Furrer21University Hospital Basel, and 2University HospitalBern, SwitzerlandReferences1. Hamlyn E, Childs K, Post FA. Reducing tu-berculosis incidence in HIV-infected patientsby tuberculin skin testing, preventive treat-ment, and antiretroviral therapy [letter]. ClinInfect Dis 2007; 44:1393–4 (in this issue).2. Elzi L, Schlegel M, Weber R, et al. Reducingtuberculosis incidence by tuberculin skin test-ing, preventive treatment, and antiretroviraltherapy in an area of low tuberculosis trans-mission. Clin Infect Dis 2007; 44:94–102.3. Rieder HL. Preventing latent tuberculosisamong HIV-infected patients: efficacious andeffective, yet inefficient? Clin Infect Dis2007; 44:103–4.4. Saukkonen JJ, Cohn DL, Jasmer RM, et al. Anofficial ATS statement: hepatotoxicity of an-tituberculosis therapy. Am J Respir Crit CareMed 2006; 174:935–52.5. Dworkin MS, Adams MR, Cohn DL, et al.Factors that complicate the treatment of tu-berculosis in HIV-infected patients. J AcquirImmune Defic Syndr 2005; 39:464–70.6. Lawn SD, Bekker LG, Miller RF. Immune re-constitution disease associated with mycobac-terial infections in HIV-infected individualsreceiving antiretrovirals. Lancet Infect Dis2005; 5:361–73.7. Hirsch HH, Kaufmann G, Sendi P, BattegayM. Immune reconstitution in HIV-infectedpatients. Clin Infect Dis 2004; 38:1159–66.8. Furrer H, Malinverni R. Systemic inflamma-tory reaction after starting highly active an-tiretroviral therapy in AIDS patients treatedfor extrapulmonary tuberculosis. Am J Med1999; 106:371–2.9. Pai M, Lewinsohn DM. Interferon-gamma as-says for tuberculosis: is anergy the Achilles’CORRESPONDENCE • CID 2007:44 (15 May) • 1395heel? Am J Respir Crit Care Med 2005; 172:519–21.10. Pai M, Riley LW, Colford JM Jr. Interferon-gamma assays in the immunodiagnosis of tu-berculosis: a systematic review. Lancet InfectDis 2004; 4:761–76.Reprints or correspondence: Dr. Hansjakob Furrer, Klinik undPoliklinik fu¨r Infektiologie, University Hospital Bern, CH-3010Bern, Switzerland (hansjakob.furrer@insel.ch).Clinical Infectious Diseases 2007; 44:1394–5 2007 by the Infectious Diseases Society of America. Allrights reserved. 1058-4838/2007/4410-0028$15.00DOI: 10.1086/518774

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