HIV co-infection is associated with reducedMycobacterium tuberculosistransmissibility in sub-Saharan Africa

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.