TB-HAART trial

Abstract

We read with interest Sayoki Mfinanga and colleagues' recent TB-HAART randomised trial in sub-Saharan Africa.1Mfinanga SG Kirenga BJ Chanda DM et al.Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial.Lancet Infect Dis. 2014; 14: 563-571Summary Full Text Full Text PDF PubMed Scopus (76) Google Scholar Initiation of antiretroviral therapy (ART) within 2 weeks of the start of pulmonary tuberculosis treatment for patients with CD4 cell counts more than 220 cells per μL did not confer any advantage over delayed ART initiation on a composite outcome of tuberculosis treatment failure, recurrence, and death. The authors concluded that comanagement of HIV infection and tuberculosis in sub-Saharan Africa remains challenging because of toxic effects, drug interactions, risk of antiretroviral drug resistance, pill burden, immune reconstitution inflammatory syndrome, and cost. Thus, they argued that WHO guidelines should be updated to recommend the delay of ART initiation until completion of tuberculosis treatment for patients with HIV and CD4 cell counts more than 220 cells per μL. Although the authors noted concern about potential toxic effects of early ART initiation, their study showed no harm in terms of mortality, grade 3 and 4 adverse events, and immune reconstitution inflammatory syndrome. However, several studies have shown that even a short deferral of ART comes at the expense of recovery of CD4-positive T cells. Deferment of ART until the completion of tuberculosis treatment could also lead to loss to follow-up and subsequent morbidity and mortality.2Kranzer K Govindasamy D Ford N Johnston V Lawn SD Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub-Saharan Africa: a systematic review.J Int AIDS Soc. 2012; 15: 17383Crossref PubMed Scopus (233) Google Scholar Initiation of ART during tuberculosis treatment enables linkage between HIV and tuberculosis treatment programmes and could improve adherence. ART integration into tuberculosis treatment settings could help to improve ART uptake among patients with tuberculosis who also have HIV.3Suthar AB Rutherford GW Horvath T Doherty MC Negussie EK Improving antiretroviral therapy scale-up and effectiveness through service integration and decentralization.AIDS. 2014; 28: S175-S185Crossref PubMed Scopus (55) Google Scholar Additionally, the ART regimen used in TB-HAART was a combination of zidovudine, lamivudine, and efavirenz. WHO guidelines recommend the use of tenofovir-based regimens, which are generally better tolerated than zidovudine.4WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. World Health Organization, Geneva2013http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdfGoogle Scholar The WHO guidelines published in 2013 recommend initiation of ART for all people living with HIV with CD4 counts 500 cells per μL. The guidelines have further promoted increased uptake of ART among HIV-positive patients with tuberculosis by removing the CD4 cell count requirement. Revision of the WHO guidelines could undo these gains by adding an additional barrier to ART initiation. We applaud Mfinanga and colleagues for doing a strong study that responds to a gap in the scientific literature. However, we believe that the benefits of early ART are convincing, from the patient-level, to the broader programmatic perspective. We argue that evidence is insufficient to change WHO guidelines. Although more operational research is being done, the worldwide health community should focus on strengthening of health systems by integration of tuberculosis and HIV clinical services. We declare no competing interests. The findings and conclusions in this Correspondence are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trialART can be delayed until after completion of 6 months of tuberculosis treatment for HIV-positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be updated accordingly. Full-Text PDF TB-HAART trial – Authors' replyWe appreciate the comments and insights on our recent Article1 from Philip Lederer and colleagues. They argue for not changing WHO guidelines on optimum timing of antiretroviral therapy (ART) in individuals infected with HIV who also have active tuberculosis. However, we do not agree with their suggestion that gains made in the promotion of ART among people living with HIV will be set back by revision of the WHO guidelines to defer ART in a select group of patients with preserved CD4 T-cell counts. 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