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NK cell phenotypic profile during active TB in people living with HIV-evolution during TB treatment and implications for bacterial clearance and disease severity.

ABSTRACT: Natural killer (NK) cells, key effector cells of the innate immune system, play an important role in the clearance and control of Mycobacterium tuberculosis and HIV infections. Here, we utilized peripheral blood specimens from the Improving Retreatment Success CAPRISA 011 study to characterize NK cell phenotypes during active TB in individuals with or without HIV co-infection. We further assessed the effects of TB treatment on NK cell phenotype, and characterized the effects of NK cell phenotypes during active TB on mycobacterial clearance and TB disease severity measured by the presence of lung cavitation. TB/HIV co-infection led to the expansion of functionally impaired CD56^neg NK cell subset. TB treatment completion resulted in restoration of total NK cells, NK cell subset redistribution and downregulation of several NK cell activating and inhibitory receptors. Higher percentage of peripheral CD56^bright cells was associated with longer time to culture conversion, while higher expression of NKp46 on CD56^dim NK cells was associated with lower odds of lung cavitation in the overall cohort and the TB/HIV co-infected participants. Together these results provide a detailed description of peripheral NK cells in TB and TB/HIV co-infection and yield insights into their role in TB disease pathology.

SUBMITTER: Maseko TG

PROVIDER: S-EPMC10359304 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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NK cell phenotypic profile during active TB in people living with HIV-evolution during TB treatment and implications for bacterial clearance and disease severity.

Maseko Thando Glory TG Rambaran Santhuri S Ngubane Slindile S Lewis Lara L Ngcapu Sinaye S Hassan-Moosa Razia R Archary Derseree D Perumal Rubeshan R Padayatchi Nesri N Naidoo Kogieleum K Sivro Aida A

Scientific reports 20230720 1

Natural killer (NK) cells, key effector cells of the innate immune system, play an important role in the clearance and control of Mycobacterium tuberculosis and HIV infections. Here, we utilized peripheral blood specimens from the Improving Retreatment Success CAPRISA 011 study to characterize NK cell phenotypes during active TB in individuals with or without HIV co-infection. We further assessed the effects of TB treatment on NK cell phenotype, and characterized the effects of NK cell phenotype ...[more]

PMID: 37474556

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Project description:IntroductionTB is the most frequent opportunistic infection and cause of death among People living with HIV/AIDS. Human immunodeficiency virus-positive individuals are routinely screened for tuberculosis as a means of monitoring efforts to mitigate the consequences of the disease on HIV-positive patients. TB status assessment identifies HIV-positive clients who show no evidence of active TB by symptom screening and would benefit from treatment with isoniazid for prevention of TB disease among HIV positives.MethodsA facility-based cross-sectional study design was conducted in public health facilities of West Shewa Zone from January to February 2019. Of the 28 Public health facilities providing HIV/AIDS care and support (HCT and ART services) 13 of them were selected by simple random sampling techniques. Finally, 815 study participants were recruited by systematics sampling techniques & proportional sample size allocation was applied depending on the HIV patient load in each health facility. After reviewing relevant literature, a structured questionnaire adapted from standardized WHO guidelines, prepared for monitoring & evaluation of TB/HIV activities was used to collect data via interviewer.ResultsOf the total, 769 (94.4%) PLHIV were screened for tuberculosis, among which 212 (27.6%) were found to be positive for active tuberculosis. Among 557 (72.4%) individuals eligible for IPT, only 300 (53.9%) were provided IPT; 257 (46.1%) eligible PLHIV were not provided IPT. Resident (adjusted odds ratio [AOR] 5.6), those who didn't attend school (AOR 4.0), primary school (grade 1-8) (AOR 3.2), and secondary school (grade 9-12) (AOR 4.2) were significantly associated with the likelihood of tuberculosis infection.ConclusionThe present study findings demonstrated that tuberculosis screening for PLHIV at West Shewa Zone public health facilities was improved in comparison with reports from many African countries and other parts of Ethiopia. The IPT implementation rate fell short of both national and WHO guidelines, notwithstanding this improvement. In the study area, diagnostic methods for tuberculosis and existing preventive measures should be improved overall.

Project description:IntroductionAmong high tuberculosis (TB) and HIV burden countries in Asia, tuberculosis preventive therapy (TPT) in people living with HIV (PLWH) has been underutilized despite its proven benefits independent of antiretroviral therapy (ART). Therefore, we determined the incidence of active TB and mortality among 9179 adult PLWH who attended and received ART from 15 tertiary care hospitals across Thailand.MethodsA retrospective study was conducted in 2018 using follow-up data from 1999 to 2018. The primary endpoint was incident TB disease after ART initiation. Factors associated with TB incidence were analysed using competing risk regression. The Kaplan-Meier method was used to estimate mortality after ART initiation.ResultsDuring a median of 5.1 years of ART (IQR 2.2-9.5 years), 442 (4.8%) PLWH developed TB (TB/HIV), giving an overall incidence of 750 (95% CI 683-823) per 100,000 persons-year of follow up (PYFU). In multivariate analysis, lower CD4 at ART initiation (≤100 cells/mm3 , adjusted sub-distribution hazard ratio [aSHR]: 2.08, 95% CI, 1.47-2.92; 101-200 cells/mm3 , aSHR: 2.21, 95% CI, 1.54-3.16; 201-350 cells/mm3 , aSHR: 1.59, 95% CI, 1.11-2.28 vs. >350 cells/mm3 ), male sex (aSHR: 1.40, 95% CI, 1.11-1.78), lower body weight (<50 kg, aSHR: 1.52, 95% CI, 1.17-1.95) and prior TB event (aSHR: 3.50, 95% CI, 2.72-4.52) were associated with TB incidence. PLWH with HIV RNA ≥50 copies/ml had 5-9 times higher risk of active TB disease higher than those with HIV RNA <50 copies/ml at the same CD4 level. The risk for developing TB was remarkably high during the initial period of ART (175,511 per 100,000 PYFU at<3 months) and was comparable to the general population after 10 years of ART (151 per 100,000 PYFU). TB/HIV had higher mortality (10% vs. 5%) and poorer HIV treatment outcomes: HIV RNA <50 copies/ml (63.8% vs. 82.8%), CD4 cells count (317 vs. 508 cells/mm3 ) at the most recent visit.ConclusionsIn this high TB burden country, TB incidence was remarkably high during the first few years after ART initiation and thereafter decreased significantly. Rapid ART initiation and appropriate TPT can be potential key interventions to tackle the TB epidemic and reduce mortality among PLWH in TB/HIV high burden settings.

Dataset Information

NK cell phenotypic profile during active TB in people living with HIV-evolution during TB treatment and implications for bacterial clearance and disease severity.

Publications

NK cell phenotypic profile during active TB in people living with HIV-evolution during TB treatment and implications for bacterial clearance and disease severity.

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