Plasma cytokines/chemokines as biomarkers of pulmonary tuberculosis culture conversion and disease severity in HIV infected and uninfected individuals in South Africa
Identification of effective biomarkers for early diagnosis, disease severity and treatment response in retreated TB individuals are urgently needed given the complex interaction between HIV and TB in hyperendemic settings. Utilising specimens from Improving Retreatment Success (IMPRESS, NCT02114684) trial we assessed the effect of soluble inflammatory markers, measured at active TB, on treatment response and disease severity in HIV infected and uninfected individuals with previous history of TB. We conducted a nested, un-matched, case (n= 31) - control (n=101) study with cases defined as those participants who failed to culture convert within 8-weeks of treatment initiation. Multiplex immunoassays and ELISA were used to measure plasma expression 24 cytokines/chemokines. Using multivariable models, we corrected for study randomization arm, HIV status, age, gender, body mass index, lung cavitation, alcohol and smoking use in the overall study cohort and we additionally corrected for viral load and CD4 count in HIV infected subgroup. Plasma IP-10 expression at active TB significantly associated with increased odds of culture conversion by 8-weeks in the overall study cohort (OR 4.255, 95% CI 1.025 – 17.544, p=0.046) and among HIV infected individuals (OR 10.204, 95% CI 1.247 – 83.333, p=0.030). IL-6 (OR 2.543, 95% CI 1.254 – 5.160, p=0.010) and IL-1RA (OR 4.639, 95% CI 1.203 – 21.031, p=0.047) expression was significantly associated with lung cavitation in the overall cohort, and in the HIV infected subgroup (IL-6: OR 2.644, 95% CI 1.062 – 6.585, p=0.037; IL-1RA: OR 7.795, 95% CI 1.177 – 51.611, p=0.033). Our results indicate that soluble inflammatory markers could be used to predict treatment response and disease severity in HIV infected and uninfected patients with recurrent TB.
Santhuri Rambaran1, Kogieleum Naidoo1,2, Razia Hassan-Moosa1, Dhineshree Govender1, Lara Lewis1, Natasha Samsunder1, Nesri Padayatchi1,2 and Aida Sivro1,3,4*
1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa
2MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, KZN, South Africa
3Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada
4Department of Medical Microbiology, University of KwaZulu-Natal, Durban, KZN, South Africa