Despite increasing access to antiretroviral therapy (ART), many HIV+ adults still present for care with severe immunosuppression. In such late presenters, mortality following ART initiation is high, curable diseases like tuberculosis (TB) or invasive bacterial diseases (IBD) being major causes of mortality. Here, we report the results of the STATIS open-label randomized controlled trial (ANRS 12290, NCT02057796) that compared the efficacy and safety of 2 strategies aiming at decreasing mortality and IBD in late presenters.
The trial was conducted in Côte d’Ivoire, Uganda, Cambodia and Vietnam. ART-naïve HIV-1 infected adults with CD4<100 cells/µl ready to start ART were randomly assigned to either ART + extensive TB screening (arm 1) or ART + systematic empirical TB treatment (4HRZE/2HR) (arm 2). In arm 1, extensive TB screening included Xpert MTB/RIF on sputum, urine lipoarabinomannan (LAM) and chest X-ray at baseline and at any time during follow-up in case of TB symptoms. ART was initiated immediately in patients who did not start TB treatment at baseline (arm 1 patients with negative TB screening) and 2 weeks after starting TB treatment in others (arm 1 patients with positive TB screening and arm 2 patients). The primary outcome was the occurrence of death or IBD at week 24 (W24). Total follow-up lasted 48 weeks. We used Cox models to compare the probability of outcomes between arms, adjusting for randomization stratification variables (country and CD4 level).
Between Sep. 2014 and May 2017, 1047 participants were included (arm 1: 525; arm 2: 522; 56% from Africa; 44% from South-East Asia). The last one reached W24 in Nov. 2017. Baseline characteristics were: 58% male, mean (SD) age 36 (9) years, body mass index 20.1 (3.5) kg/m2, hemoglobin 11.6 (2.3) g/dl, CD4 36 (27) cells/µl, plasma HIV RNA 5.4 (0.6) log10 copies/ml, with no difference between arms. At W24, 39 patients (3.8%) were lost to follow-up (arm 1: 21; arm 2: 18), while there were 69 deaths (arm 1: 36; arm 2: 33) and 29 IBD (arm 1: 14; arm 2: 15) (Figure). The W24 hazard ratio of events between arm 2 vs. arm 1 was 0.93 (95%CI 0.61-1.42) for death or IBD, 0.92 (0.57-1.48) for death alone, 1.14 (0.54-2.40) for IBD alone and 2.70 (1.80-4.04) for grade 3-4 drug-related toxicity.
Systematic TB treatment is not superior to extensive TB screening using Xpert MTB/RIF and urine LAM and targeted TB treatment to decrease the risk of mortality or IBD in ART-naïve adults ready to start ART with CD4<100/µl.