The delivery of new tuberculosis vaccines to people living with HIV – when to vaccinate?

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality in people living with HIV (PLHIV). New TB vaccines may help reduce this burden. There is limited data on the response to new TB vaccines in PLHIV and how this may vary with levels of immunosuppression and anti-retroviral therapy (ART). The potential interaction between vaccine efficacy and ART raises questions about the optimum timing of vaccination against TB in PLHIV. Methods: Using a simple cumulative risk model, we compared the impact of different TB vaccination strategies for PLHIV. We compared the impact of vaccinating at linkage to HIV care, to the impact of vaccinating at ART initiation. We explored how the optimum timing of vaccination depends on characteristics of the vaccine and the ART program at an individual and population level. Results: For an individual, the optimum timing of vaccination against TB is at ART initiation unless the time to ART initiation is more than 6 months or if the reduction in vaccine efficacy when given prior to ART is small. At a population level, the proportion of PLHIV who initiate ART is a key determinate of the optimum strategy. If ART uptake is low, it would be better to vaccinate at linkage to HIV care, even if vaccine efficacy in ART naïve individuals is less than 50% of efficacy in individuals on ART. Conclusions: Our results suggest that the optimum timing of new TB vaccination for PLHIV will depend on the relative efficacy of vaccination in ART-naïve individuals vs individuals on ART, and the uptake and timing of ART initiation. If vaccine efficacy is lower among ART-naïve individuals, improvements in HIV programs may help maximize the impact of new TB vaccines.