Same-day testing with initiation of antiretroviral therapy or tuberculosis treatment versus standard care for persons presenting with tuberculosis symptoms at HIV diagnosis: A randomized unblinded trial

Abstract

Background: Same-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment would be superior to standard care in this population. Methods and Findings: We conducted an open-label randomized trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day treatment [TB medication if TB; ART if no TB]) vs. standard care. In both groups, ART was initiated two weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA <200 copies/mL, with intention to treat analysis. From November 6, 2017 to January 16, 2020, 500 participants were randomized (250/group). Baseline TB was diagnosed in 40 (16.0%) in the standard and 48 (19.2%) in the same-day group; all initiated TB treatment. In the standard group, 245 (98.0%) initiated ART at median of 9 days; 6 (2.4%) died, 229 (91.6%) were retained, and 220 (88.0%) received 48-week HIV-1 RNA testing; 168 had <200 copies/mL (among randomized: 67.2%; among tested: 76.4%). In the same-day group, 249 (99.6%) initiated ART at median of 0 days; 9 (3.6%) died, 218 (87.2%) were retained, and 211 (84.4%) received 48-week HIV-1 RNA; 152 had <200 copies/mL (among randomized: 60.8%; among tested: 72.0%). There was no difference between groups in the primary outcome (60.8% vs. 67.2%; risk difference: -0.06; 95% CI: -0.15, 0.02; p=0.14). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain. Conclusions: In patients with TB symptoms at HIV diagnosis, same-day treatment is not associated with superior retention and viral suppression. A short delay in ART initiation, which facilitates more feasible TB testing, does not compromise outcomes.

Same-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: protocol for an open-label randomized non-inferiority trial in Lesotho and Malawi

“…SaDAPT is a pragmatic randomized non-inferiority trial conducted in Malawi and Lesotho that compares the effectiveness and safety of SDI of ART ("ART first") to ART initiation only after results of TB investigations are available ("TB results first") in PWH with presumptive TB. A previous trial assessing the effectiveness of SDI in presumptive TB has provided same-day NAAT results as part of the trial procedures and then started ART only in participants found to be TB negative (42). However, this turnaround time for NAAT is not feasible in many settings.…”

Predictors of Clinical Outcomes among People with HIV and Tuberculosis Symptoms after Rapid Treatment Initiation in Haiti

“…We included all participants enrolled in the original trial in this secondary analysis. 12 Patients were eligible for inclusion in the trial if they had documented HIV-1 infection, were ≥18 years of age, ART-naïve, and reported cough, fever, and/or night sweats of any duration, and/or weight loss. Exclusion criteria included tuberculosis treatment in the past year, lack of preparedness on an ART readiness questionnaire, pregnancy or breastfeeding, active drug or alcohol use, a mental condition that would interfere with completing study requirements, plans to transfer during the study period, symptoms consistent with WHO stage 4 neurologic disease, or WHO "danger signs" of temperature >39 degrees Celsius, pulse >120 beats/minute, respiratory rate >30 breaths/minute, or inability to walk unaided.…”

“…Study procedures have been reported in detail elsewhere. 12 For the purposes of this analysis, we included baseline demographic, clinical and laboratory data, as well as outcome data 48 weeks after enrollment, all of which were extracted from the GHESKIO electronic health record. Baselines variables included in this analysis were: age, sex, income less than $1 USD per day (self-report), educational attainment, marital status, body mass index (BMI), CD4 cell count, tuberculosis diagnosis (microbiologically or clinically diagnosed), and study arm (same-day or standard).…”

“…Since the publication of these guidelines, our group has demonstrated high rates of ART initiation and retention in care among people with HIV and tuberculosis symptoms in Haiti who were randomized to either of two rapid treatment initiation strategies. 12 While the recently shifting approach in ART initiation timing reflects the clearly apparent benefits associated with a rapid start, this strategy necessitates a shorter window of time to allow for the assessment of clinical or social risk factors for poor outcomes after initiating ART. As a result, a key research priority in the rapid ART initiation era is to identify readily available baseline characteristics associated with subsequent treatment outcomes such as retention in care, viral suppression, and mortality.…”

“…To address this gap in the literature, we evaluated baseline predictors of clinical outcomes in a randomized trial of two rapid treatment initiation strategies for people with HIV and tuberculosis symptoms receiving care in urban Haiti. 12…”