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Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV.

Sullivan ZA, Wong EB, Ndung'u T, Kasprowicz VO, Bishai WR - EBioMedicine (2015)

Bottom Line: Interestingly, T-cell activation was elevated individuals with both latent and active TB.These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic.In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression.

View Article: PubMed Central - PubMed

Affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.

ABSTRACT

In recent years, chronic immune activation and systemic inflammation have emerged as hallmarks of HIV disease progression and mortality. Several studies indicate that soluble inflammatory biomarkers (sCD14, IL-6, IL-8, CRP and hyaluronic acid), as well as surface markers of T-cell activation (CD38, HLA-DR) independently predict progression to AIDS and mortality in HIV-infected individuals. While co-infections have been shown to contribute to immune activation, the impact of latent tuberculosis infection (LTBI), which is widely endemic in the areas most affected by the global AIDS epidemic, has not been evaluated. We hypothesized that both active and latent states of Mycobacterium tuberculosis co-infection contribute to elevated immune activation as measurable by these markers. In HIV-infected individuals with active, but not latent TB, we found elevated levels of soluble markers associated with monocyte activation. Interestingly, T-cell activation was elevated individuals with both latent and active TB. These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic. In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression.

No MeSH data available.


Related in: MedlinePlus

Plasma concentrations of A) soluble CD14 (sCD14), B) C-reactive protein (CRP), C) IL-6, D) IL-8, E) interferon gamma-induced protein 10 (IP-10), and F) hyaluronic acid in HIV-infected individuals with no evidence of M. tb infection (no TB), latent TB (LTBI), and active TB (AT). Subjects represented here were members of the iThimba cohort. p-Values reported for Mann Whitney U test, with a threshold for significance of 0.0083 after Bonferroni correction. p-Values greater than 0.0083 not displayed. Data displayed as median with interquartile range.
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f0005: Plasma concentrations of A) soluble CD14 (sCD14), B) C-reactive protein (CRP), C) IL-6, D) IL-8, E) interferon gamma-induced protein 10 (IP-10), and F) hyaluronic acid in HIV-infected individuals with no evidence of M. tb infection (no TB), latent TB (LTBI), and active TB (AT). Subjects represented here were members of the iThimba cohort. p-Values reported for Mann Whitney U test, with a threshold for significance of 0.0083 after Bonferroni correction. p-Values greater than 0.0083 not displayed. Data displayed as median with interquartile range.

Mentions: Our first aim was to assess the effect of latent and active TB infection on soluble inflammatory biomarkers that have been shown to predict poor outcomes in HIV-infected individuals. We measured plasma levels of sCD14, CRP, IL-6, IL-8, IP-10, and hyaluronic acid in HIV-infected subjects with no evidence of TB infection (no TB), latent TB infection (LTBI), and active TB disease (AT, Table 1). We found no significant differences between levels of these plasma biomarkers for individuals with no TB versus those with LTBI (Fig. 1). Individuals with active TB had higher levels of sCD14 (p = 0.0076), CRP (p = 0.022), IL-6 (p = 0.0040) and IP-10 (p = 0.0185, not significant after Bonferroni correction). Similarly, individuals with active TB had higher levels of sCD14 (p = 0.0012), CRP (p < 0.0001), IP-10 (p = 0.003), IL-6 (p < 0.0001) and IL-8 (p = 0.0130, not significant after Bonferroni correction) than those with no evidence of TB. Levels of hyaluronic acid did not vary significantly between the three groups.


Latent and Active Tuberculosis Infection Increase Immune Activation in Individuals Co-Infected with HIV.

Sullivan ZA, Wong EB, Ndung'u T, Kasprowicz VO, Bishai WR - EBioMedicine (2015)

Plasma concentrations of A) soluble CD14 (sCD14), B) C-reactive protein (CRP), C) IL-6, D) IL-8, E) interferon gamma-induced protein 10 (IP-10), and F) hyaluronic acid in HIV-infected individuals with no evidence of M. tb infection (no TB), latent TB (LTBI), and active TB (AT). Subjects represented here were members of the iThimba cohort. p-Values reported for Mann Whitney U test, with a threshold for significance of 0.0083 after Bonferroni correction. p-Values greater than 0.0083 not displayed. Data displayed as median with interquartile range.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4476549&req=5

f0005: Plasma concentrations of A) soluble CD14 (sCD14), B) C-reactive protein (CRP), C) IL-6, D) IL-8, E) interferon gamma-induced protein 10 (IP-10), and F) hyaluronic acid in HIV-infected individuals with no evidence of M. tb infection (no TB), latent TB (LTBI), and active TB (AT). Subjects represented here were members of the iThimba cohort. p-Values reported for Mann Whitney U test, with a threshold for significance of 0.0083 after Bonferroni correction. p-Values greater than 0.0083 not displayed. Data displayed as median with interquartile range.
Mentions: Our first aim was to assess the effect of latent and active TB infection on soluble inflammatory biomarkers that have been shown to predict poor outcomes in HIV-infected individuals. We measured plasma levels of sCD14, CRP, IL-6, IL-8, IP-10, and hyaluronic acid in HIV-infected subjects with no evidence of TB infection (no TB), latent TB infection (LTBI), and active TB disease (AT, Table 1). We found no significant differences between levels of these plasma biomarkers for individuals with no TB versus those with LTBI (Fig. 1). Individuals with active TB had higher levels of sCD14 (p = 0.0076), CRP (p = 0.022), IL-6 (p = 0.0040) and IP-10 (p = 0.0185, not significant after Bonferroni correction). Similarly, individuals with active TB had higher levels of sCD14 (p = 0.0012), CRP (p < 0.0001), IP-10 (p = 0.003), IL-6 (p < 0.0001) and IL-8 (p = 0.0130, not significant after Bonferroni correction) than those with no evidence of TB. Levels of hyaluronic acid did not vary significantly between the three groups.

Bottom Line: Interestingly, T-cell activation was elevated individuals with both latent and active TB.These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic.In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression.

View Article: PubMed Central - PubMed

Affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa ; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.

ABSTRACT

In recent years, chronic immune activation and systemic inflammation have emerged as hallmarks of HIV disease progression and mortality. Several studies indicate that soluble inflammatory biomarkers (sCD14, IL-6, IL-8, CRP and hyaluronic acid), as well as surface markers of T-cell activation (CD38, HLA-DR) independently predict progression to AIDS and mortality in HIV-infected individuals. While co-infections have been shown to contribute to immune activation, the impact of latent tuberculosis infection (LTBI), which is widely endemic in the areas most affected by the global AIDS epidemic, has not been evaluated. We hypothesized that both active and latent states of Mycobacterium tuberculosis co-infection contribute to elevated immune activation as measurable by these markers. In HIV-infected individuals with active, but not latent TB, we found elevated levels of soluble markers associated with monocyte activation. Interestingly, T-cell activation was elevated individuals with both latent and active TB. These results suggest that in the highly TB- and HIV-endemic settings of southern Africa, latent TB-associated T-cell activation may contribute to HIV disease progression and exacerbate the HIV epidemic. In addition, our findings indicate that aggressive campaigns to treat LTBI in HIV-infected individuals in high-burden countries will not only impact TB rates, but may also slow HIV progression.

No MeSH data available.


Related in: MedlinePlus