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. 2025 Aug 13;21(8):e1013350.
doi: 10.1371/journal.ppat.1013350. eCollection 2025 Aug.

Infection with Mycobacterium tuberculosis alters the antibody response to HIV-1

Marius Zeeb  1   2 , Katharina Kusejko  1   2 , Sonja Hartnack  3 , Chloé Pasin  1   2 , Irene A Abela  1   2 , Peter Rusert  2 , Thomas Liechti  2 , Claus Kadelka  2 , Julia Notter  4 , Anna Eichenberger  5 , Matthias Hoffmann  6 , Hans H Hirsch  7   8   9 , Alexandra Calmy  10   11 , Matthias Cavassini  12 , Niklaus D Labhardt  13   14 , Enos Bernasconi  11   15   16 , Huldrych F Günthard  1   2 , Roger D Kouyos  1   2 , Alexandra Trkola  2 , Johannes Nemeth  1 ; and the Swiss HIV Cohort Study
Affiliations

Infection with Mycobacterium tuberculosis alters the antibody response to HIV-1

Marius Zeeb et al. PLoS Pathog. .

Abstract

Background: Co-infection with Mycobacterium tuberculosis (MTB) differentially modulates untreated HIV-1 infection, with asymptomatic MTB reducing HIV-1 viremia and opportunistic infections and active tuberculosis (TB) accelerating AIDS progression. Here, we investigate antibody (Ab) responses to HIV-1 in people with HIV (PWH) without MTB, with asymptomatic MTB, and with later progression to active TB to elucidate MTB-associated effects on HIV-1 immune control.

Methods: Using the Swiss HIV Cohort Study (SHCS), we conducted a retrospective study that included 2,840 PWH with data on MTB status and HIV-1-specific plasma binding-/neutralizing-responses. We evaluated associations between MTB status and binding-/neutralizing-responses while adjusting for key disease and demographic parameters.

Results: Among the included 2,840 PWH, 263 PWH had asymptomatic MTB based on either a positive TST-/IGRA-test at the baseline (time of HIV-1 Ab measurement) or on later progression to active TB. Compared to PWH without MTB infection, PWH with asymptomatic MTB infection showed reduced HIV-1 Ab levels, both for Env binding (e.g., IgG1 BG505 trimer antigen, p = 0.024) and neutralization of a diverse panel of HIV-1 viruses (p = 0.012). Conversely, PWH (n = 32) who later progressed to active TB (>180 days after baseline) demonstrated a significant shift towards IgG3 in their HIV-1 Ab repertoire (p = 0.011), detectable in median 3.8 years (IQR 2.4 - 8.7) before active TB onset.

Conclusion: Our data indicate that asymptomatic MTB infection and active TB exert profound heterologous effects on HIV-1 specific Ab development. These findings advance our understanding of host-pathogen dynamics and may have implications for new diagnostic approaches in predicting future active TB.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: K.K. has received research grants unrelated to this work from the Swiss National Science Foundation. I.A.A. received research grants from the Swiss HIV Cohort Study, Gilead and travel expenses from Gilead for research unrelated to this work. J.No. received research grants unrelated to this work from the Swiss HIV Cohort Study and the cantonal hospital St. Gallen, paid to her institution, and travel expenses from Gilead unrelated to this work. M.C. received research grants unrelated to this work from Gilead, ViiV and MSD, paid to his institution; payment for expert testimony unrelated to his work from Gilead, ViiV and MSD, paid to his institution; and travel expenses unrelated to this work from Gilead, paid to his institution. A.E. received honoraria for presentations unrelated to this work from Bavarian Nordic, paid to her institution; and honoraria for advisory board consultations unrelated to this work from ViiV and Gilead, paid to her institution. E.B. received research grants unrelated to this work from MSD, paid to his institution; consulting fees unrelated to this work from Moderna, paid to his institution; honoraria for presentations unrelated to this work from Pfizer, paid to his institution; travel expenses unrelated to this work from ViiV, MSD, Gilead and Pfizer, paid to his institution; and honoraria for data safety monitoring board or advisory board consultations unrelated to this work from ViiV, MSD, Pfizer, Gilead, Moderna, AstraZeneca, AbbVie and Ely Lilly, paid to his institution. H.F.G. has received research grants unrelated to this work from the Swiss National Science Foundation, Swiss HIV Cohort Study, Yvonne Jacob Foundation, NIH, Gilead, ViiV and Bill and Melinda Gates foundation, paid to his institution; personal honoraria for data safety monitoring board or advisory board consultations unrelated to this work from Merck, ViiV healthcare, Gilead Sciences, Janssen, Johnson and Johnson, Novartis and GSK. R.D.K. received research grants unrelated to this work from Gilead and NIH, paid to his institution. All other authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study population selection.
People with HIV from the SHCS and Swiss 4.5k screen included and excluded depended on their MTB status. Abbreviations: IGRA (Interferon gamma release assay), MTB (Mycobacterium tuberculosis), SHCS (Swiss HIV Cohort Study), TB (Tuberculosis), TST (tuberculin skin test). Figure was created with Microsoft PowerPoint and icons from UXWing (https://uxwing.com/antibodies-icon/; https://uxwing.com/bacteria-icon/).
Fig 2
Fig 2. People with HIV-1 and asymptomatic MTB infection exhibit reduced HIV-1 plasma neutralization and antigen binding.
A: Comparison of neutralization score at baseline between PWH with- and without asymptomatic MTB infection. Each box depicts the interquartile range (IQR), each vertical line extends to the most extreme value within 1.5 IQR from the box, and each horizontal line depicts the median. B: Adjusted comparison with demographic characteristics and HIV-1 disease specific parameters. The p value and effect estimates were determined with a tobit regression. C: Association between asymptomatic MTB infection and HIV-1 antigen plasma binding response, adjusted for demographic characteristics and HIV-1 disease specific parameters. RNA unadjusted corresponds to regression models not adjusted for HIV-1 RNA viral load. The effect estimates were determined with a linear regression and the confidence intervals were adjusted based on the p values adjusted for multiple testing using the Benjamini-Hochberg procedure.
Fig 3
Fig 3. Elevated HIV-1 specific IgG3 response associated with progression to active TB.
A. Kaplan-Meier curves of time to active TB progression from baseline, stratified by tertiles of combined HIV-1 specific IgG Ab class response. The p values estimates were determined with a log rank test. Cumulative number of censoring indicates the number people with loss to follow-up B: Comparison of the HIV-1 specific IgG3 Ab response against individual antigens between PWH with an asymptomatic MTB infection with (n = 32) and without (n = 231) later progression to active TB. P values were calculated with a two tailed Student’s t test.
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