In 2012, at 22 antiretroviral therapy (ART) clinics, Botswana implemented a phased rollout of the Xpert package of interventions, with 3 components: (1) additional nurses and mentoring to support intensified tuberculosis (TB) case finding (ICF) activities, (2) intensified tracing for patients missing clinic appointments, and (3) Xpert MTB/RIF (Xpert) replacing smear microscopy. We evaluated effect of the Xpert package on early (6- and 12-month) ART mortality in the XPRES trial (ClinicalTrials.gov: NCT02538952).
At 22 ART clinics, all adult patients (>12 years old) starting ART were enrolled in three phases: (1) a retrospective standard of care (SOC) phase, (2) a prospective enhanced care (EC) phase, and (3) a prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were enrolled as a stepped-wedge trial. Adults enrolled in the EC phase received SOC plus components 1 (TB ICF) and 2 (intensified tracing) of the Xpert package. Adults enrolled in the EC+X phase received SOC plus all 3 components of the Xpert package. All-cause 6-month ART mortality was the primary outcome. An adjusted analysis, appropriate for study design, controlled for baseline differences in individual-level factors and intra-facility correlation. Trial outcome results are final.
14,963 eligible patients were enrolled; 8,980 in the SOC, 1,768 in the EC, and 4,215 in the EC+X phases. Median age of ART enrollees was 35 years, 64% were female, median weight was 58.4 kg, and median hemoglobin 11.7 g/dL. These characteristics were similar across phases. Pregnancy among females was less common in the SOC than subsequent phases (16% in SOC, 23% in EC, and 32% in EC+X). Median CD4 count at ART initiation was lower in SOC than subsequent phases (184/µL in SOC, 241/µL in EC, and 246/µL in EC+X). In adjusted analysis, compared with the SOC phase, 6-month ART mortality was significantly lower in the EC+X phase, while 12-month ART mortality was significantly lower in both the EC and EC+X phases (Table). When compared with the EC phase, 6- and 12-month mortality rates were not significantly different in the EC+X phase.
In Botswana, interventions to strengthen TB ICF and active tracing were associated with lower early ART mortality and should be considered for scale-up. No additional mortality benefit of replacing smear microscopy with Xpert was observed.