Abstract
AbstractPersons living with HIV are known to be at increased risk of developing tuberculosis (TB) disease upon infection withMycobacterium tuberculosis(Mtb). However, it has remained unclear how HIV co-infection affects subsequentMtbtransmission from these patients. Here, we customized a Bayesian phylodynamic framework to estimate the effects of HIV co-infection on theMtbtransmission dynamics from sequence data. We applied our model to fourMtbgenomic datasets collected in sub-Saharan African countries with a generalized HIV epidemic. Our results confirm that HIV co-infection is a strong risk factor for developing active TB. Additionally, we demonstrate that HIV co-infection is associated with a reduced effective reproductive number for TB. Stratifying the population by CD4+ T-cell count yielded similar results, suggesting that, in this context, CD4+ T-cell count is not a better predictor ofMtbtransmissibility than HIV infection status. Together, our genome-based analyses complement observational household studies, and firmly establish the negative association between HIV co-infection andMtbtransmissibility.Author summaryMany sub-Saharan African countries have seen a considerable rise in TB incidence since the introduction of HIV, suggesting a strong interaction between HIV and TB epidemics. HIV infection is recognized as an important risk factor for developing TB, but the contribution of HIV-infected TB patients to furtherMtbtransmission is poorly understood. In this study, we analyzed four sets ofMtbgenomic sequences collected in different countries, including sequences from HIV-negative and HIV-positive TB patients. We applied a phylodynamic model to these sequences, aimed at inferring transmission dynamics within and between different host populations. While our findings support that HIV is a strong risk factor for TB, we show that HIV-positive TB patients generate a significantly lower number of secondary TB cases than HIV-negative patients. This suggests that HIV-positive patients often act as sinks inMtbtransmission chains, while HIV-negative patients are a major source of transmission.
Publisher
Cold Spring Harbor Laboratory