Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV

PLoS Biol. 2020 Dec 7;18(12):e3000963. doi: 10.1371/journal.pbio.3000963. eCollection 2020 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / complications
  • AIDS-Related Opportunistic Infections / etiology
  • AIDS-Related Opportunistic Infections / microbiology
  • Adult
  • CD4-Positive T-Lymphocytes
  • Cohort Studies
  • Disease Progression
  • Female
  • HIV Infections / complications*
  • HIV Infections / metabolism
  • HIV-1 / pathogenicity
  • Humans
  • Interferon-gamma
  • Latent Tuberculosis / complications*
  • Latent Tuberculosis / diagnosis*
  • Latent Tuberculosis / metabolism
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / pathogenicity
  • Opportunistic Infections / complications
  • Risk
  • Tuberculosis / complications
  • Tuberculosis / diagnosis
  • Viral Load / immunology

Substances

  • Interferon-gamma

Grants and funding

Swiss National Science Foundation (SNF, http://p3.snf.ch) (grant numbers 33CS30_177499 and 324730B_179571), received by HFG. Yvonne-Jacob Foundation (https://stiftungen.stiftungschweiz.ch/organizations/stiftung-yvonne-jacob), received by HFG. SNF (grant numbers PZ00P3-142411 and BSSGI0_155851), received by RDK. SNF (grant number P300PB_164742), and grant for scientific development from the University Hospital Zurich, received by JN. SHCS research foundation (Number 857), received by JN. Unrestricted research grant from Gilead Sciences, to the SHCS research foundation. None of the funders had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.