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Duration of isoniazid preventive therapy in HIV-infected patients – Authors' reply

2011; Elsevier BV; Volume: 378; Issue: 9798 Linguagem: Inglês

10.1016/s0140-6736(11)61533-x

1474-547X

Taraz Samandari, Themba Moeti, Elizabeth A. Talbot, Tefera Agizew, Samba Nyirenda,

Diagnosis and treatment of tuberculosis

Our study's genesis and design were based on the hypothesis that 6 months of isoniazid preventive therapy was inadequate to prevent tuberculosis in HIV-infected people living in endemic settings. 6 months' treatment was selected as the control group because it was at the time both the WHO recommendation and Botswana's policy.1AnonPreventive therapy against tuberculosis in people living with HIV: policy statement.Wkly Epidemiol Rec. 1999; 74: 385-398PubMed Google Scholar We regard with caution Hans Rieder's position that 9 or 12 months of isoniazid should have been the control treatment. Rieder cites two papers to support this position. The first paper was from a European trial done in the pre-HIV era in individuals with a positive tuberculin skin test (TST) and fibrotic lesions on chest radiographs. Of our TST-positive cohort, 93% had normal radiographs. Although none of the participants in the European trial was free of fibrotic lesions, this paper showed that among participants with lesions of less than 2 cm2, there was no difference in tuberculosis incidence between 6-month and 12-month isoniazid recipients. This finding suggests that people with smaller (and presumably absent) radiographic lesions do not derive any benefit beyond 6 months. The second paper Rieder cites examined tuberculosis rates in Alaskans grouped by their estimated intakes of isoniazid. Although this analysis has been influential, its strength cannot be compared with results of randomised controlled trials. To date, no trial has compared 6 months versus 9 or 12 months of isoniazid preventive therapy in HIV-infected people living in tuberculosis-endemic countries. Rieder doubts that the benefit of 36 months' isoniazid preventive therapy was through the prevention of reinfection—a consideration that we had not dismissed in our paper. He comments, though, that 12 months' isoniazid preventive therapy in Alaska Natives had a two-decade-long benefit despite a high rate of reinfection. It should be recalled that the small Alaska Native population benefited from multiple tuberculosis control interventions including “case-finding, isolation and treatment” and were free of HIV.2Comstock GW Philip RN Decline of the tuberculosis epidemic in Alaska.Public Health Rep. 1961; 76: 19-24Crossref PubMed Scopus (33) Google Scholar, 3Johnson MW Results of 20 years of tuberculosis control in Alaska.Health Services Rep. 1973; 88: 247-254Crossref PubMed Scopus (8) Google Scholar Furthermore, whereas the aforementioned European study showed that the benefit of 6 months' isoniazid preventive therapy lasted at least 5 years, studies in Africa showed that in HIV-infected recipients of isoniazid preventive therapy, tuberculosis rates returned to levels as high as placebo recipients' as early as 6 months after treatment completion.4Quigley MA Mwinga A Hosp M et al.Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults.AIDS. 2001; 15: 215-222Crossref PubMed Scopus (131) Google Scholar, 5Johnson JL Okwera A Hom DL et al.Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults.AIDS. 2001; 15: 2137-2147Crossref PubMed Scopus (145) Google Scholar Although we earnestly wish for multipronged, Alaska-style tuberculosis control measures for the large populations of tuberculosis-endemic countries, 36 months' isoniazid preventive therapy is now a proven, WHO-recommended option for the most tuberculosis-vulnerable population of HIV-infected people accessing care. We agree with Naveen Dutt that isoniazid preventive therapy is best targeted for TST-positive individuals and that each country should determine the appropriateness of isoniazid preventive therapy on the basis of isoniazid-resistance rates in new tuberculosis patients. We declare that we have no conflicts of interest. Duration of isoniazid preventive therapy in HIV-infected patientsTaraz Samandari and colleagues (May 7, p 1588)1 conclude that 36 months' isoniazid preventive therapy was more effective than a 6-month course, giving a 74% relative reduction in tuberculosis incidence. This is similar to the 77% reduction in the 5-year incidence among “completer-compliers” in a large trial comparing 12 with 6 months of treatment.2 This latter approach was used in a cost-effectiveness study, providing the rationale for the American Thoracic Society (ATS) to shift emphasis to 6 months. Full-Text PDF Duration of isoniazid preventive therapy in HIV-infected patientsTaraz Samandari and colleagues1 recommend 36 months of isoniazid prophylaxis for prevention of tuberculosis in individuals with HIV. In their study, isoniazid prophylaxis was given to all HIV patients residing in areas with a prevalence of latent tuberculosis of more than 30%. Most of the countries with a high prevalence of HIV and tuberculosis are developing countries with economic constraints. Isoniazid prophylaxis has been found to have little benefit in individuals with a negative tuberculin skin test (TST),2 so unnecessary exposure of such individuals to the side-effects of isoniazid and the associated waste of resources cannot be advocated. Full-Text PDF