HIV co-infection is associated with reduced Mycobacterium tuberculosis transmissibility in sub-Saharan Africa

Abstract

Persons living with HIV are known to be at increased risk of developing tuberculosis (TB) disease upon infection with Mycobacterium tuberculosis (Mtb). However, it has remained unclear how HIV co-infection affects subsequent Mtb transmission from these patients. Here, we customized a Bayesian phylodynamic framework to estimate the effects of HIV co-infection on the Mtb transmission dynamics from sequence data. We applied our model to four Mtb genomic 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 of Mtb transmissibility than HIV infection status alone. Together, our genome-based analyses complement observational household contact studies, and more firmly establish the negative association between HIV co-infection and Mtb transmissibility.

Fig 1. Posterior maximum clade credibility trees of Mtb isolates from Tanzania.

Posterior maximum clade credibility trees per lineage, summarizing the posterior tree distribution resulting from the phylodynamic analyses on the Mtb sequences from Tanzania, with tips labeled by HIV infection status. Trees of isolates from the other locations are shown in S4–S6 Figs.

Fig 2. Phylodynamic estimates of the effects of HIV co-infection on Mtb transmission.

Prior (grey) and posterior (coloured) distributions per sampling location of the estimates for a) the relative risk of developing active TB upon exposure (HIV-positive relative to HIV-negative individuals), b) the relative R_e for TB. For all posterior distributions, the 95% HPD intervals do not contain 1.

Fig 3. CD4+ T-cell count as predictor of Mtb transmissibility and TB disease progression.

Prior (grey) and posterior (coloured) distributions per sampling location of the estimates for a) the relative risk of developing active TB upon exposure (individuals with low CD4+ T-cell count relative to individuals with high CD4+ T-cell count), b) the relative R_e for TB. A threshold of 350 CD4+ T-cells/μl was used to classify patients. For all posterior distributions, the 95% HPD intervals do not contain 1.