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 3.89/100 pys. 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 1.49/100 pys for TST-negatives, and 1.05/100 and 1.64/100 pys 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.

Projecting the impact of variable MDR-TB transmission efficiency on long-term epidemic trends in South Africa and Vietnam.

Whether multidrug-resistant tuberculosis (MDR-TB) is less transmissible than drug-susceptible (DS-)TB on a population level is uncertain. Even in the absence of a genetic fitness cost, the transmission potential of individuals with MDR-TB may vary by infectiousness, frequency of contact, or duration of disease. We used a compartmental model to project the progression of MDR-TB epidemics in South Africa and Vietnam under alternative assumptions about the relative transmission efficiency of MDR-TB. Specifically, we considered three scenarios: consistently lower transmission efficiency for MDR-TB than for DS-TB; equal transmission efficiency; and an initial deficit in the transmission efficiency of MDR-TB that closes over time. We calibrated these scenarios with data from drug resistance surveys and projected epidemic trends to 2040. The incidence of MDR-TB was projected to expand in most scenarios, but the degree of expansion depended greatly on the future transmission efficiency of MDR-TB. For example, by 2040, we projected absolute MDR-TB incidence to account for 5% (IQR: 4-9%) of incident TB in South Africa and 14% (IQR: 9-26%) in Vietnam assuming consistently lower MDR-TB transmission efficiency, versus 15% (IQR: 8-27%)and 41% (IQR: 23-62%), respectively, assuming shrinking transmission efficiency deficits. Given future uncertainty, specific responses to halt MDR-TB transmission should be prioritized.