Discussion
TB, AIDS, TB-IRIS, viral suppression, initiation and retention
AIDS, SECONDARY, OIS
The results of this randomized trial show that in patients with TB symptoms at initial HIV diagnosis, a short delay in treatment initiation does not appear to compromise outcomes, compared with same-day treatment. The findings of this study do not confirm our hypothesis that same-day TB assessment and same-day treatment with TB medication or ART would improve retention with viral suppression in this patient population. We did not detect a statistically significant difference between groups in any primary or secondary outcome, except that the standard group was more likely to achieve 48-week viral suppression at the cut-off of <50 copies/mL. An important caveat is that treatment was provided rapidly in the standard group, with median time to ART initiation of only 7 days in those not diagnosed with TB, which meets WHO criteria for rapid ART initiation [In prior randomized trials which found superior rates of retention and viral suppression with same-day ART, including a study conducted at our site in Haiti, the majority of standard group participants delayed ART initiation for weeks to months after HIV diagnosis [In contrast to our approach, in which all participants received at least 1 Xpert Ultra result prior to ART initiation, participants in the intervention group in the Simplified Algorithm for Treatment Eligibility (SLATE) II study with nonserious TB symptoms and a negative urine point-of-care lipoarabinomannan antigen of mycobacteria (LAM) test were eligible for same-day ART, with next-day tracing to contact those with positive Xpert MTB/RIF results [Eighteen percent of participants in our study cohort were diagnosed with TB at baseline. Though a small number started ART prior to TB diagnosis, and about 20% presented with CD4 counts <100 cells/mmThe implications of our study findings are that a short delay in treatment initiation does not appear to be associated with inferior outcomes. Within the model of differentiated service delivery, patients do not all have the same needs. Same-day ART is ideal for many patients, and may be preferred at sites that can perform same-day Xpert MTB/RIF testing, which may eliminate the need for a return visit for test results. In contrast, in large sites such as ours, with centralized laboratories, the provision of same-day Xpert MTB/RIF results may be logistically complicated. An alternative approach would be initiating ART while Xpert results are pending, but we agree with the systematic review which concluded that there is insufficient evidence to recommend this strategy in settings with high burdens of TB [It is critical to emphasize that the GHESKIO approach includes more than just ART initiation, as other successful programs have also described [Nearly two-thirds of the total study cohort achieved the primary outcome of retention in care with 48-week viral suppression. Retention rates were high, but viral suppression rates were suboptimal in both groups, though similar to global estimates from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium [Our study was conducted among nonpregnant, ART-naïve participants in a large urban clinic, which may limit the generalizability of our findings. Moreover, the quality of care which is provided at GHESKIO is high, as evidenced by the rapid time to ART initiation in both groups in this study. It is also noteworthy that we utilized a more aggressive diagnostic approach for TB than is generally provided in usual care, which may have contributed to our lack of TB-IRIS. In addition, all participants received medication for prophylaxis of OIs or symptomatic relief on the day of HIV diagnosis, which may have contributed to our high retention rate in the standard group. However, we note the prescription of non-ART medications on the day of HIV diagnosis is common practice in many settings. We also used an ART Readiness Assessment for eligibility in the study. It is possible that patients who failed this assessment would have preferentially benefited from the same-day treatment intervention, but we note that <5% of patients failed this assessment.In conclusion, our results indicate that same-day treatment does not appear to be associated with superior outcomes, compared with standard care, for patients who present with TB symptoms at HIV diagnosis. Our findings indicate that either strategy—same-day TB testing with initiation of same-day treatment or a short delay in ART initiation for TB assessment—is associated with high rates of ART initiation and retention in care.