Dataset Information

Plasma Cytokine Predictors of Tuberculosis Recurrence in Antiretroviral-Treated Human Immunodeficiency Virus-infected Individuals from Durban, South Africa.

ABSTRACT:

Background

Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure.

Methods

Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB. At baseline, ART was initiated, and TB successfully cured. Participants were screened for TB recurrence quarterly for up to 4 years. TB recurrent cases (n = 63) were matched to controls (n = 123) on sex, study arm assignment in the original trial, and month of enrollment with a subset of cases sampled longitudinally at several time-points.

Results

Three cytokines were associated with increased rates of TB recurrence in univariate models: interleukin 6 (IL6) (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.34-5.28, P = .005), IP10 (OR 4.62, 95% CI 1.69-12.65, P = .003), monokine induced by IFN-? (MIG) (OR 3.11, 95% CI 1.10-8.82, P = .034). Conversely, interferon ? (IFN?) was associated with decreased TB risk (OR 0.34, 95% CI 0.13-0.87, P = .025). Following multivariate analyses adjusting for covariates IL6, interleukin 1? (IL1?), and interleukin 1R? (IL1R?) were associated with increased risk and IFN? with decreased TB risk. Longitudinal analysis showed that levels of many TB-associated markers, including IL6, IP10, sCD14, and interferon ? (IFN?) are reduced following TB treatment.

Conclusion

These data show that TB recurrence, in HIV-infected individuals on ART is predicted by biomarkers of systemic inflammation, many of which are implicated in more rapid HIV disease progression.

Clinical trials registration

NCT 01539005.

SUBMITTER: Sivro A

PROVIDER: S-EPMC5848260 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Plasma Cytokine Predictors of Tuberculosis Recurrence in Antiretroviral-Treated Human Immunodeficiency Virus-infected Individuals from Durban, South Africa.

Sivro Aida A McKinnon Lyle R LR Yende-Zuma Nonhlanhla N Gengiah Santhana S Samsunder Natasha N Abdool Karim Salim S SS Naidoo Kogieleum K

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20170901 5

<h4>Background</h4>Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure.<h4>Methods</h4>Study participants were drawn from a prospective cohort study initiated at the conclusion ...[more]

PMID: 29017282

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Project description:BackgroundSouth Africa has the largest population of human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART) realising the benefits of increased life expectancy. However, this population may be susceptible to cardiovascular disease (CVD) development, due to the chronic consequences of a lifestyle-related combination of risk factors, HIV infection and ART. We predicted a 10-year cardiovascular mortality risk in an HIV-infected population on long-term ART, based on their observed metabolic risk factor profile.MethodsWe extracted data from hospital medical charts for 384 randomly selected HIV-infected patients aged ≥ 30 years. We defined metabolic syndrome (MetS) subcomponents using the International Diabetes Federation definition. A validated non-laboratory-based model for predicting a 10-year CVD mortality risk was applied and categorised into five levels, with the thresholds ranging from very low-risk (< 5%) to very high-risk scores (> 30%).ResultsAmong the 384 patients, with a mean (± standard deviation) age of 42.90 ± 8.20 years, the proportion of patients that were overweight/obese was 53.3%, where 50.9% had low high-density lipoprotein (HDL) cholesterol and 21 (17.5%) had metabolic syndrome. A total of 144 patients with complete data allowed a definitive prediction of a 10-year CVD mortality risk. 52% (95% CI 44-60) of the patients were stratified to very low risk (< 5%) compared to 8% (95% CI 4-13) that were at a very high risk (> 30%) of 10-year CVD mortality. The CVD risk grows with increasing age (years), 57.82 ± 6.27 among very high risk and 37.52 ± 4.50; p < 0.001 in very low risk patients. Adjusting for age and analysing CVD risk mortality as a continuous risk score, increasing duration of HIV infection (p = 0.002) and ART (p = 0.007) were significantly associated with increased predicted 10 year CVD mortality risk. However, there was no association between these factors and categorised CVD mortality risk as per recommended scoring thresholds.ConclusionsApproximately 1 in 10 HIV-infected patients is at very high risk of predicted 10-year CVD mortality in our study population. Like uninfected individuals, our study found increased age as a major predictor of 10-year mortality risk and high prevalence of metabolic syndrome. Additional CVD mortality risk due to the duration of HIV infection and ART was seen in our population, further studies in larger and more representative study samples are encouraged. It recommends an urgent need for early planning, prevention and management of metabolic risk factors in HIV populations, at the point of ART initiation.

Dataset Information

Plasma Cytokine Predictors of Tuberculosis Recurrence in Antiretroviral-Treated Human Immunodeficiency Virus-infected Individuals from Durban, South Africa.

Background

Methods

Results

Conclusion

Clinical trials registration

Publications

Plasma Cytokine Predictors of Tuberculosis Recurrence in Antiretroviral-Treated Human Immunodeficiency Virus-infected Individuals from Durban, South Africa.

Similar Datasets

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