CD4⁺ cell count stratification to guide tuberculosis preventive therapy for people living with HIV

Objectives:In 2018, Brazilian guidelines changed to recommend tuberculosis (TB) preventive therapy for all people with HIV and a CD4⁺ cell count 350 cells/μl or less, but only for those with a positive tuberculin skin test (TST) if CD4⁺ cell count is than 350 cells/μl. We determined the potential effectiveness of CD4⁺-based guidelines for TB testing and preventive therapy.Design:Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT).Methods:We analyzed data from 4114 newly registered patients with HIV in 29 clinics followed until TB diagnosis, death, or administrative censoring. We compared incidence rates of TB and TB/death between CD4⁺, TST, IPT, and antiretroviral therapy categories.Results:Initial CD4⁺ cell count was 350 cells/μl or less in 2138 (52%) and more than 350 cells/μl in 1976 (48%) patients. TST was performed for 2922 (71%), of whom 657 (16%) were TST-positive [278 (13%) CD4⁺≤350 vs. 379 (19%) CD4⁺>350]. A total of 619 (15%) received IPT and 2806 (68%) received antiretroviral therapy. For patients with CD4⁺ cell count 350 cells/μl or less who did not receive IPT, the incidence rate of TB was 1.79/100 person-years (pys) and TB/death was 3.89/100pys. For patients with CD4⁺ cell count more than 350 who did not receive IPT, the incidence rates of TB and TB/death were 0.57/100 and 1.49/100pys for TST-negatives, and 1.05/100 and 1.64/100pys for TST-unknowns.Conclusion:TB incidence was high among all patients who did not receive IPT, including those with CD4⁺ cell count more than 350 cells/μl and negative or unknown TST results. TB preventive therapy should be provided to all people living with HIV in medium burden settings, regardless of CD4⁺ cell count and TST status.