Abstract

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.

Highlights

  • Models suggest that Mycobacterium tuberculosis (MTB) might have emerged as a human pathogen around 400,000 years ago [1]

  • We assessed the association of Latent Tuberculosis Infection (LTBI) infection or active TB with HIV set point viral load (SPVL) and the development of opportunistic infection (OI) at the population level in a prospective, nationwide clinical cohort

  • Compared to MTB uninfected patients, LTBI was associated with a significant decrease in HIV SPVL, suggesting new and exciting interactions between LTBI and HIV

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Summary

Introduction

Models suggest that Mycobacterium tuberculosis (MTB) might have emerged as a human pathogen around 400,000 years ago [1]. Over this long period, MTB and humans have evolved to reach a balance; MTB infects many people—approximately 28% of the human population have been exposed to MTB [2]—but over 90% of infected individuals do not develop disease [3]. This framework neglects a basic understanding about how LTBI itself alters human biology

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