Systematic Empirical vs. Test-guided Anti-tuberculosis Treatment Impact in Severely Immunosuppressed HIV-infected Adults Initiating Antiretroviral Therapy With CD4 Cell Counts <100/mm3: the STATIS Randomized Controlled Trial
Systematic Empirical vs. Test-guided Anti-tuberculosis Treatment Impact in Severely Immunosuppressed HIV-infected Adults Initiating Antiretroviral Therapy With CD4 Cell Counts <100/mm3: the STATIS Randomized Controlled Trial
In countries with a high tuberculosis (TB) prevalence, TB and invasive bacterial infections are leading causes of early death in patients who initiate antiretroviral therapy (ART) with advanced immunodeficiency.
We hypothesize that a systematic 6-month empirical TB treatment initiated 2 weeks before the introduction of ART in HIV-infected adults with severe immunosuppression (CD4<100/mm3) and no overt evidence of TB will reduce the risk of death and invasive bacterial infections. This strategy will be compared to one of extensive TB testing using point-of-care tests (Xpert MTB/RIF® and urine lipoarabinomanan LAM) and chest X-ray to identify and treat only patients with at least one positive test suggestive of TB.
Settings: Cambodia, Côte d'Ivoire, Uganda, Vietnam. Design: Multicentre, two-arm, unblinded randomized controlled superiority trial.
Objective: To compare the 24-week risk of death and occurrence of invasive bacterial infection between two experimental strategies in HIV-1 infected adults who start ART with a CD4 count <100/mm3: (i) continuous extensive TB screening during follow-up each time the patient present with symptoms, versus (ii) systematic empirical TB treatment started 2 weeks before ART initiation.
Trial strategies:
At inclusion, participants will be randomized 1:1 in two strategies of TB testing and treatment: extensive TB screening, or systematic empirical TB treatment.
Extensive TB screening (arm 1): In this arm:
Systematic empirical TB treatment (arm 2): In this arm:
Both strategies will apply to the first 24 weeks in the trial (intervention period).
From week-24 to week-48, the choice of TB tests and the prescription of TB treatment will be left upon the decision of the investigator in both trial arms.
Inclusion time: 24 months. Follow-up: each patient will be followed 48 weeks. Statistical analysis: the primary analysis will be intention to treat. It will compare the 24-week probability of death or invasive bacterial infection between arms.
Sample size: 1050 participants. This will allow demonstration of a 40% reduction in the 24-week probability of death or invasive bacterial infection in arm 2, compared to arm 1 (α 5%; 1-β 80%).
Inclusion Criteria:
Exclusion Criteria: