Is it time for Brazil to prioritize TB preventive therapy for all people living with HIV?

Dear Editor:

People living with HIV (PLWH) in Brazil have a tuberculosis (TB) cure rate of 49.1%, while preventive therapy for latent tuberculosis infection (LTBI) is vastly underutilized in this high-risk population. Historically, the Brazilian TB control program's primary focus is similar to all other high burden settings, emphasizing diagnosis and treatment of active disease with little energy is expended toward contact investigations and preventive therapy.¹

Brazilian guidelines recommend isoniazid preventive therapy (IPT) for 6 months using a dose of 300 mg/day, but only for PLWH and adult and child household contacts who have a positive tuberculin skin test (TST).¹ A cluster randomized trial² showed that offering TST and IPT, as per Brazilian guidelines, significantly reduced TB risk and mortality among PLWH, however almost 40% of patients never received a TST, thus limiting impact of the intervention.² A follow-up study decisively reported that patients receiving IPT had long-term protection from TB.³ In 2006, a preventive therapy regimen of rifapentine plus isoniazid given once weekly for three months (3HP) was shown to be effective in Brazil.⁴ More recently, 3HP proved as effective as isoniazid alone in a multi-country study, including Brazil, for people living with⁵ and without HIV.⁶ Based on this evidence, the Brazilian NTP has initiated the process of incorporating the 3HP regimen.

The National TB and AIDS programs have worked independently for decades. However, the programs have improved communications in recent years and are developing collaborative actions focused on LTBI in PLWH. A more effective and efficient approach would see the AIDS program take responsibility for IPT as they have for other disease prevention,^7,8 and the development of surveillance system for notification and monitoring of cases of latent TB, the latter of which is currently in development.

Finally, Brazil is facing the global shortage of tuberculin,⁹ thus few TSTs are available country-wide, leading to alternate, but more expensive approaches to diagnosing latent TB, including interferon gamma release assays. If barriers exist toward diagnosing LTBI, then Brazil must consider moving toward universal LTBI treatment for PLWH, or targeting particular high-risk subgroups among this population who are at high risk of progression to disease. A modified strategy would initiate preventive therapy for all PLWH unless a negative test for LTBI was known, and halt treatment if and when a negative test is determined. Thus, PLWH who have no history of an LTBI test, the overwhelming majority of PLWH in Brazil, would initiate preventive therapy. Such a policy shift could lead to substantial reductions in disease incidence and will certainty improve TB control toward the 2035 WHO targets.

REFERENCES

• ¹
  Ministério da Saúde (BR). Secretaria de Vigilância em saúde. Manual de recomendações para o controle da tuberculose no Brasil; 2011.
• ²
  Durovni B, Saraceni V, Moulton LH, et al. Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomised trial. Lancet Infect Dis. 2013;13:852-8.
• ³
  Golub JE, Cohn S, Saraceni V, et al. Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected patients in a medium-burden tuberculosis setting: the TB/HIV in Rio (THRio) study. Clin Infect Dis. 2015;60:639-45.
• ⁴
  Schechter M, Zajdenverg R, Falco G, et al. Weekly rifapentine/isoniazid or dail rifampin/pyrazinamide for latent tuberculosis in household contacts. Am J Respir Crit Care Med. 2006;173:922-6 (Epub ahead of print).
• ⁵
  Sterling TR, Scott NA, Miro JM, et al., Tuberculosis Trials Consortium, the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259) The investigators of the TB Trials Consortium and the AIDS Clinical Trials Group for the PREVENT TB Trial are listed in the Supplement, item 17. AIDS. 2016;30:1607–15.
• ⁶
  Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365:2155-66.
• ⁷
  Ministério da Saúde (BR). Departamento de DST, Aids e Hepatites Virais. O Manejo da Infecção pelo HIV na Atenção Básica: Manual para profissionais médicos. Departamento de DST, Aids e Hepatites Virais; 2015.
• ⁸
  Saraceni V, Pacheco AG, Golub JE, et al. Physician adherence to guidelines for tuberculosis and HIV care in Rio de Janeiro, Brazil. Braz J Infect Dis. 2011;15:249-52.
• ⁹
  Coordenação Geral do Programa Nacional de Controle da Tuberculose, Secretaria de Vigilância em Saúde, Departamento de Vigilância das Doenças Transmissíveis, Ministério da Saúde. Ofício Circular no 25/CGPNCT/DEVIT/SVS/MS. Dificuldades na aquisição do derivado proteico purificado – PPD. http://www.cve.saude.sp.gov.br/htm/TB/eventos/TB_OfCircular25_PPD.pdf [accessed 11.05.17].
  » http://www.cve.saude.sp.gov.br/htm/TB/eventos/TB_OfCircular25_PPD.pdf

Publication Dates

• Publication in this collection
  Jan-Feb 2018

History

• Received
  29 July 2017
• Accepted
  20 Oct 2017