Xpert MTB/RIF Cycle Threshold as a Marker of Tuberculosis (TB) Disease Severity: Implications for TB Treatment Stratification

Grint D.J.; Dhillon J.; Butcher P.D.; Adams J.; Munshi T.; Witney A.A.; Gould K.; Laing K.; Cousins C.; Wasserman S.; Fielding K.; Harrison T.; Jindani A.; Harrison T.; Butcher P.; Robb C.; Patel N.; Shah N.; Abdelmalik S.; Burton S.; Kirwan D.; Witney A.; Fielding K.; Grint D.; Barer M.; Decker J.; Mukamolova G.; Waddell S.; Boyd A.F.R.; Agizew T.; Tshikuka J.G.; Tlhakanelo J.T.; Mathoma A.; Mathebula U.; Basotli J.; Mawoko N.D.; Mowaneg G.; Dintwa E.; Masole M.; Masono M.; Atwine D.; Byamukama A.; Taremwa I.M.; Orikiriza P.; Deborah Nanjebe K.T.; Nyehangane D.; Kananura K.; Kyohairwe R.; Akatuhebwa S.L.; Lydia D.K.; Arimpa A.; Mbabazi Y.S.; Kamulegeya D.; Natukunda E.; Asiimwe B.; Mucunguzi E.; Arinaitwe R.; Birungi D.; Nimusima C.; Ashaba J.; Bonnet M.; Camara L.M.; Bah O.Y.; Bah B.; Nzabintwali F.; Djeima D.A.; Mme M.N.M.; Maimouna S.; Bah M.A.; Conde M.; Bah K.S.; Bah F.; Karamoko S.; Barry A.; Balde M.K.; Harouna A.B.; Mamadou B.; Barry S.; Barry A.S.; Chávez E.T.; Huaroto L.; Pérez V.M.C.; Páucar J.G.S.; Huaroto C.E.T.; Pineda P.R.R.M.; Condorhuamán W.S.G.; Vergaray G.E.; Flores V.C.; Vergaray J.T.; Lorenzo L.V.; Valverde M.E.V.; López M.I.; Onofre W.V.; Salazar K.C.; Infantes M.B.; Vásquez Y.R.J.; Echevarría J.C.; Aguilar R.P.; Mantari G.E.A.; Quispe M.Q.; Diaz I.A.C.; Cruz J.J.Z.; Burgos M.; Shrestha B.; Shrestha N.M.; Tandukar S.; Maharjan B.; Tandukar B.; Raya B.B.; Maharjan M.; Karki S.; Shrestha M.; Hamid S.; Jamil B.; Begum D.; Ahmed I.; Hasan R.; Muhammad I.; Muzammil A.; Shahzad P.; Adil A.; Jawed H.; Sultan F.; Hassan M.; Masood I.; Nizamuddin S. · Clinical Infectious Diseases (2026) · DOI: 10.1093/cid/ciaf527

Resumen

Background Recent trials have demonstrated that shortened 4-month treatment durations are effective for the majority of people with tuberculosis (TB). However, there is a population of patients with TB who require longer treatment durations. Prospectively identifying those who require shorter versus longer treatment durations would support evaluation and implementation of optimized regimens. Methods We analyzed data from the RIFASHORT TB treatment-shortening noninferiority trial to define a TB phenotype classification. The RIFASHORT trial primary outcome was reanalyzed using the protocol-defined noninferiority criterion of 8 percentage points, stratifying by those classified as having limited or extensive disease. Results Xpert MTB/RIF semiquantitative bacterial burden in combination with TB disease involvement grading on chest X-ray achieved the strongest differentiation between relapse and nonrelapse. The extensive disease TB phenotype (high semiquantitative bacterial burden and extensive TB disease on X-ray) accounted for one-quarter of the RIFASHORT trial population and more than half of all posttreatment TB relapses (13/23). For the limited TB disease phenotype (a semiquantitative bacterial burden other than high or no extensive TB disease on X-ray), the experimental 4-month 1200-mg rifampicin-containing regimen met the protocol-defined noninferiority criterion in both modified intention-to-treat (adjusted risk difference: -1.3%; 95% CI, -6.7% to 4.0%) and per protocol analyses (1.7%; 95% CI, -3.8% to 7.1%). Conclusions The TB phenotype classification derived here successfully identified three-quarters of RIFASHORT trial participants for whom a 4-month 1200-mg rifampicin regimen was noninferior to the 6-month standard of care. A definitive phase III randomized trial of disease-stratified rifampicin-based TB treatment is justified.

Instituciones: Universidad Nacional Mayor de San Marcos