Association between HIV co-infection and delayed diagnosis with tuberculosis bacterial load in setting with widespread antiretroviral therapy use

HIV co-infection has been shown to be associated with lower tuberculosis (TB) bacterial load in studies conducted prior to widespread availability of antiretroviral therapy (ART). We investigated associations between HIV co-infection and TB bacterial load, accounting for differences in time to TB diagnosis, in a high prevalence setting with widespread ART use. In Gaborone, Botswana, 268 sputum samples from people with newly diagnosed TB were tested with Xpert MTB/RIF Ultra (Xpert). TB bacterial load and time to TB diagnosis were estimated using mean Xpert cycle threshold (CT) and symptom duration, respectively. Multiple linear regression models and causal mediation analysis were used to determine the associations between HIV and Xpert CT and assess the mediating effect of symptom duration. Mean CT values were higher in people living with HIV compared to people without HIV (22.7 vs 20.3, p < 0.001). Among those living with HIV, there was a negative relationship between CD4 count and mean CT value (Spearmans rho -0.20, p = 0.06). After controlling for gender, age, and symptom duration, HIV status remained associated with CT value, with an average increase of 1.6 cycles (p = 0.009) among people with HIV and CD4 count > 200 cells/mm3 and 2.1 cycles (p = 0.002) in those with a CD4 count [&le;] 200 cells/mm3 compared to individuals without HIV. Symptom duration was also found to be associated with CT value (p < 0.05). We found an indirect effect of HIV status on Xpert CT through the mediator, symptom duration ({beta} = 0.33, p = 0.048), accounting for 13.5% of the relationship. Our findings suggest that time to TB diagnosis partially mediates the relationship between HIV status and CT value, but differences in pathophysiology between people with and without HIV likely play a dominant role in affecting TB bacterial burden.