Resistance to tuberculin skin test/interferon-gamma release assay conversion among highly TB exposed, HIV infected goldminers in South Africa

Abstract

Background A small proportion of goldminers in South Africa resist tuberculin skin test (TST)/interferon-gamma release assay (IGRA) conversion despite high rates of HIV and prolonged exposure to TB. We conducted a study among HIV-infected goldminers to determine the: i) proportion who resisted TST/IGRA conversion and ii) epidemiological factors associated with resistance to TST/IGRA conversion. Methods We enrolled HIV-infected goldminers who were on antiretroviral treatment, aged 33–60 years, with ≥15 years’ service, no prior or current TB, no silicosis, and with body mass index >18.5 kg/m2. TST/IGRA conversion was assessed at baseline, 6 months, and 12 months using TST and QuantiFERON-TB-Gold-Plus (QFT-Plus). Miners were considered resisters if they had a zero TST response and a negative QFT-Plus at all visits. Logistic regression was used to identify epidemiological factors associated with TST/IGRA conversion resistance. Results We enrolled 245 HIV-infected miners with median age of 48 years (interquartile-range [IQR]: 44–52 years) and median CD4 count, 506 cells/ µ L (IQR: 372–677 cells/ µ L). Overall, 98.4% (241) were males and 99.2% (243) were Black/African with a median time of 24 years (IQR: 18–29 years) in the workforce. Of those completing all follow-ups, 24.3% (50/206) resisted TST/IGRA conversion. Miners who had a history of taking isoniazid preventive therapy (IPT) (adjusted odds ratio (aOR) 2.34; 95% confidence interval (CI): 1.14–4.80; p = 0.020) were more likely to resist TST/IGRA conversion. However, those from Mozambique (aOR 0.16; 95% CI: 0.04–0.71; p = 0.016) and those who had a CD4 count ≥500 cells/ µ L (aOR 0.46; 95% CI: 0.23–0.92; p = 0.028) were less likely to resist TST/IGRA conversion. Conclusion Similar to previous longitudinal cohort studies, we found a small proportion of HIV-infected goldminers who resisted TST/IGRA conversion. This was positively associated with prior IPT, but negatively associated with lower CD4 count and being from Mozambique. However, mechanisms underlying TST/IGRA conversion resistance are not well understood.