March 31, 2020 – Last week, Treatment Action Group was pleased to receive the World Health Organization’s (WHO) update to its guidance on TB preventive therapy (TPT). Both the updated guidelines and operational handbook on TPT are available here.
Key Updates in the Updated Guidelines Include:
I. The addition of 1HP (one month of daily rifapentine and isoniazid) and 4R (four months of daily rifampicin) to the list of TPT regimens recommended by the WHO.
The full list of WHO-recommended TPT options now includes:
- 1HP: one month of rifapentine plus isoniazid given daily
- 3HP: three months of rifapentine plus isoniazid given weekly
- 3HR: three months of rifampicin plus isoniazid given daily
- 4R: four months of rifampicin alone given daily
- 6–36H: six to 36 months of isoniazid alone given daily (IPT)
The TPT regimens listed above are not in any rank order, and the WHO has not indicated a preference for one regimen over another. Choice of regimen should be informed by multiple factors, including age, potential toxicities, interactions with other medications, and individual values and preferences. All of these recommended regimens can be used in people living with HIV (PLHIV), and all can be self-administered (i.e., there is no DOT requirement).
II. The continued recommendation that pregnant women living with HIV have the choice to take IPT during pregnancy.
A randomized controlled trial (RCT) of IPT in pregnant and postpartum women living with HIV reported a higher risk of adverse pregnancy outcomes when women initiated IPT during pregnancy compared to postpartum. The WHO determined that these findings were insufficient to change WHO policy when evaluated against the totality of evidence (most of it from observational studies that did not confirm the findings of the RCT). In addition, the guideline development group “considered that systematic deferral of IPT to the postpartum [period] would deprive women from its protective effect at a point when they are more vulnerable to TB.” As a result, pregnancy does not disqualify women living with HIV from receiving IPT.
The updated guidance suggests that rifampicin is generally considered safe during pregnancy, so rifampicin-based TPT is an alternative to IPT for pregnant women. However, there are limited data available to inform the safety of rifapentine-based TPT during pregnancy, though a recent pharmacokinetic study concluded that no rifapentine dose adjustments are necessary for 3HP during pregnancy or the postpartum period. To fully inform women deciding whether to take rifapentine during pregnancy, an RCT powered to determine optimal timing and safety of 3HP and 1HP during pregnancy is necessary and should be initiated with urgency.
III. Confirmation that PLHIV on dolutegravir-based ART can receive the rifapentine-based 3HP regimen without any dolutegravir dose adjustments or safety concerns
Of note, the study that determined PLHIV on dolutegravir can safely take 3HP only enrolled people already on ART. A follow-on study is underway to evaluate whether these findings hold for people newly initiating ART and 3HP simultaneously.
IV. Perhaps most importantly, the revised WHO TPT recommendations are more universal than previous ones.
The recommendations are no longer segmented by TB incidence thresholds. In past guidance, some recommendations applied to low-TB-incidence countries but not to high-incidence countries. Such ‘double standards’ were motivated by concerns about differences among countries in levels of TB transmission, programmatic capacity, and the availability and affordability of newer regimens. In these updated guidelines, such factors are discussed under “implementation considerations.” We believe this is a more equitable approach than applying recommendations differentially based on TB incidence.
TAG has always strongly believed that access to the highest attainable standard of TB prevention is a human right. For more information on how activists can support equitable access to TPT, please see TAG’s An Activist’s Guide to Rifapentine, which is soon to be updated.
Advocates and members of civil society may reach out to TAG with questions on advocacy for TPT at any time, and we encourage you to do so.