Successful implementation of TPT in people living with HIV requires a comprehensive approach across multiple programmatic areas. National programmes may prioritize the use of 3HP as the preferred regimen in people living with HIV. While a preferential recommendation is beneficial, national programmes must still maintain access to alternative recommended options such as 6H/9H, and enable the use of 1HP, 3RH and 4R in special circumstances: this demands context-specific flexibility in areas and populations where rifapentine is unavailable or contraindicated, in pregnant women and children, or in persons exposed to multidrug-/rifampicin-resistant TB who may require tailored options. National health authorities need to facilitate regulatory approvals, include drugs on essential medicines and procurement lists, and step up efforts to secure sustainable funding from both domestic and external sources. TPT should be embedded within routine ART services and included in the training syllabus for health workers, who need to know about appropriate regimen use, TB screening, and managing sideeffects and drug-drug interactions with ARVs. Monitoring and evaluation systems should track regimenspecific initiation, adherence and outcomes to feed into programme decisions and improve coverage. Community engagement is essential to address stigma, promote TPT as a critical lifesaving intervention and gain adherence through peer support, digital tools and incentives. Tailored approaches are needed for special populations, including regimen choices for pregnant women and children, and expanded access to child-friendly formulations. Regimen prioritization • Prioritize 3HP as the preferred TPT regimen; guide transition as needed.

• Maintain access to 6H/9H alternatives; guarantee availability of 1HP, 3RH, 4R 6Lfx for use in special circumstances. Regulatory and financing • Register rifapentine* and update national guidelines.
• Secure sustainable financing from domestic and external sources. Services integration • Embed TPT provisions into ART services and maternal and child care.
• Train health workers on TPT regimens, TB screening and management of side-effects and drug-drug interactions with ARVs. Access and supply chain • Add rifapentine to national essential medicines lists.
• Ensure procurement and consistent supply of rifapentine, including FDC.
• Facilitate national, regional and global mechanisms to assure reliable access to shorter regimens in countries (In several high TB-burden LMIC countries, rifapentine is not registered, despite its inclusion in WHO’s list of essential medicines and its approval by the US Food and Drug Administration (FDA); it still awaits registration with the European Medicine Agency (EMA)) Monitoring and evaluation • Track TPT initiation, adherence and outcomes by regimen.
• Use data to inform programme decisions and improve coverage. Community engagement • Address stigma issues and promote TPT as essential lifesaving intervention for people living with HIV along with ART.
• Support counselling and adherence support through peer, digital and incentive-based approaches. Special populations • Offer choice of regimens for pregnant women and children.
• Ensure availability of child-friendly formulations.
• Secure options for key and vulnerable populations. Pharmacokinetic studies indicate that co-administration of 3HP, dolutegravir and efavirenz is generally safe and there is no need to adjust the ARV dose; nevertheless, regular clinical monitoring during TPT should be provided (29). Limited data on the use of 3HP during pregnancy provide preliminary reassurance about its safety, with studies showing no significant increase in adverse pregnancy outcomes compared to traditional regimens (30). Some studies assessing the preferences of health care providers and patients have found a strong preference for 3HP over daily regimens such as 6H, 9H and even 1HP, due to its shorter duration, lower pill burden and less frequent dosing, all of which align better with routine HIV care workflows and reduce patient fatigue