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

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. Trial Registration This study is registered with [ClinicalTrials.gov][1] [NCT03154320][2] ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03154320 ### Funding Statement This study was funded by a grant from the National Institute of Allergy and Infectious Diseases (R01AI131998; primary investigator: SK). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the institutional review boards at GHESKIO, Mass General Brigham, Florida International University, and Weill Cornell Medical College I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03154320&atom=%2Fmedrxiv%2Fearly%2F2022%2F12%2F30%2F2022.12.28.22283999.atom