Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis

Abstract

Background Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. Methods We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. Results A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log10 copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P = 0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. Conclusions Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.)

Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy

“…In patients with pulmonary TB early ART initiation is associated with improvements in AIDS-free survival, particularly in patients with low baseline CD4 counts 27 . In patients with HIV-associated TBM, however, our previous study suggested that immediate ART did not result in a survival benefit, but was associated with an increase in severe adverse events 28 .…”

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…All HIV‐infected children diagnosed with TB should also be started on ART; however, the optimal timing of ART initiation depends on the degree of immunocompromise. Adult RCTs showed significant reduction in mortality and progression to AIDS with earlier ART in patients with CD4 counts < 50 cells/μl (Starting ART at 3 Points in TB (SAPIT) 162, Cambodian Early versus Late Introduction of Antiretrovirals (CAMELIA) 163 and Immediate Versus Deferred Start of Anti‐ HIV Therapy in HIV ‐Infected Adults Being Treated for Tuberculosis (STRIDE) 164). A retrospective study in South African children, most of whom were severely immunocompromised with median CD4 percentage < 12%, also showed that delay of ART for longer than 2 months was associated with increased mortality and worse virological response 165.…”

Quels enjeux de recherche trente ans après l’identification du virus VIH ?

“…Les co-infections restent un problème majeur, en particulier la tuberculose et les hépatites virales, aussi bien au Nord qu'au Sud. L'étude ANRS/NIH Camelia [6], réalisée au Cambodge, avait ouvert la voie à la prise en charge optimale de la co-infection VIH et tuberculose. Dans le domaine des hépatites virales, nous sommes en pleine révolution en matière de traitement de l'hépatite C, avec l'arrivée d'une nouvelle classe de molécules, les « directacting antivirals » (DAA), qui vont permettre à court/moyen terme de se passer de l'interféron pégylé.…”