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. 2023 Jun 1;37(7):1065-1075.
doi: 10.1097/QAD.0000000000003523. Epub 2023 Mar 3.

Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy

Tecla M Temu  1   2 , Stephen J Polyak  3 , Celestine N Wanjalla  4 , Nelson Aringo Mandela  5 , Smritee Dabee  6 , Jerusha N Mogaka  1 , Sarah Masyuko  5 , Chris Longernecker  1   7 , Saate Shakil  7 , Bhavna Chohan  1 , Stephanie T Page  7 , Sylvia M Lacourse  1   7 , Bernard Gitura  5 , Kristina Crothers  7 , Julius Oyugi  2 , Heather Jaspan  6 , Carey Farquhar  1   7   8 , Jerry S Zifodya  9
Affiliations

Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy

Tecla M Temu et al. AIDS. .

Abstract

Background: Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults.

Methods: We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI-, HIV-LTBI+, HIV-LTBI-). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors.

Results: Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models ( P < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants ( P < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV-LTBI- ( P < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4 + T-cell count and ART duration.

Conclusions: Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Fig. 1
Fig. 1
Log10 plasma levels of biomarkers by HIV serostatus and LTBI status.
Fig. 2
Fig. 2
Association of LTBI and HIV with plasma biomarkers.
See this image and copyright information in PMC

References

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