Abstract
BACKGROUND: Although there are sex and HIV differences in tuberculosis (TB) prevalence, the underlying mechanisms are incompletely understood. Few studies have evaluated whether sex and HIV modify the inflammatory response to TB. METHODS: Adults with pulmonary TB with and without HIV in Kampala, Uganda had 12 immune activation biomarkers measured at TB diagnosis and at completion of therapy. Associations between biomarkers and sex were assessed using multivariable regression models at baseline and follow-up after adjusting for age, HIV status, and AFB smear grade. Given evidence of sex-HIV interaction in several biomarkers, models were stratified by HIV status. RESULTS: Overall, 151 participants were included and 74 (49%) were female. Forty-nine (32%) participants had HIV; 21 (43%) of those with HIV were female. At baseline, biomarkers were overall higher in men, whereas at follow-up, suPAR ( P < 0.001) and sCD163 were higher in women ( P = 0.02) and IL-6 ( P = 0.01) and IFABP ( P = 0.02) were higher in men. After stratifying by HIV status, at baseline, most of the biomarkers were higher in men without HIV and there were no sex differences in those with HIV. At follow-up, women without HIV had higher levels of suPAR ( P = 0.01) and sCD163 ( P = 0.051). Women with HIV had higher levels of suPAR, C-reactive protein, and IP-10 ( P < 0.05 for all); no other sex differences were observed. CONCLUSIONS: Among adults with pulmonary TB in Uganda, men had greater immune activation than women only in the absence of HIV. After treatment, women tended to have more immune activation than men in the setting of HIV.