Incomplete restoration of Mycobacterium tuberculosis-specific-CD4 T cell responses despite antiretroviral therapy

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• 作者：Denise C. Hsu^a ; ^b ; ^{d.hsu@amr.org.au" class="auth_mail} ; Stephen J. Kerr^a ; ^b ; Parawee Thongpaeng^b ; Thatri Iampornsin^b ; Sarah L. Pett^a ; ^c ; ^d ; John J. Zaunders^a ; ^c ; Anchalee Avihingsanon^b ; Sasiwimol Ubolyam^b ; Jintanat Ananworanich^b ; Anthony D. Kelleher^a ; ^c ; David A. Cooper^a ; ^c
• 关键词：MTB-specific-CD4 T cells ; Immune restoration ; Tuberculosis ; HIV infection ; Antiretroviral therapy
• 刊名：Journal of Infection
• 出版年：April, 2014
• 年：2014
• 卷：68
• 期：4
• 页码：344-354
• 全文大小：1208 K

文摘

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Summary

Objectives

Despite antiretroviral therapy (ART), HIV-infected persons have increased risk of active tuberculosis (TB). PPD and combined ESAT-6 and CFP-10-specific-CD4 (EC-Sp-CD4) responses were examined over 96 weeks.

Methods

HIV-infected, ART-naive Thai adults with CD4 T cell count 鈮?50聽cells/渭L starting ART were assessed at baseline, wk4, 8, 12, 24, 48 and 96. PPD and EC-Sp-CD4 T cells were detected by CD25/CD134 co-expression after stimulation with antigens.

Results

Fifty subjects were enrolled, 39 were male, median age 32 yrs, median baseline CD4 T cell count 186聽cells/渭L and plasma HIV-viral-load 4.9log₁₀聽copies/mL. Seventeen were TB-sensitised.

At baseline, 25 had positive PPD and 15 had positive EC-Sp-CD4 response. CD4 T cell count <100聽cells/渭L was less (P聽=聽0.005) and TB-sensitisation was more likely (P聽=聽0.013) to be associated with positive baseline PPD-Sp-CD4 response.

At wk4, the number of subjects with positive PPD-Sp-CD4 response rose to 35 (P聽=聽0.021). Mean PPD-Sp-CD4 T cells increased at wk4 (P聽=聽0.017) in patients not classified as TB-sensitised.

The number of subjects with positive EC-Sp-CD4 response did not change significantly post ART. In TB-sensitised patients, mean EC-Sp-CD4 T cells declined to below baseline from wk12 (P聽=聽0.010) onwards. EC-Sp-CD4 responses were undetectable in 3 out of 17 TB-sensitised patients.

Conclusions

Restoration of responses to TB-antigens was incomplete and inconsistent under the employed experimental conditions and may account for persistent increased risk of TB despite ART.