Abstract
Are There Sex-Specific Differences in Response to Adjunctive Host-Directed Therapies for Tuberculosis?
Highlights
Tuberculosis (TB) appears to afflict men more than women, but the underlying reasons for this disparity and whether there are sex-based differences in TB treatment responses are unknown
It has already been established that sex must be considered in preclinical studies, clearly defined “go/no-go” endpoints to justify further testing of various host-directed therapy (HDT) agents in clinical trials have yet to be defined
It is unknown if the antiTB activity of statins and other promising HDTs are sex specific
Summary
Tuberculosis (TB) appears to afflict men more than women, but the underlying reasons for this disparity and whether there are sex-based differences in TB treatment responses are unknown. Based on a knowledge gap in previously published studies, a pertinent research question is being asked: Are there sex-specific differences in response to adjunctive host-directed therapy (HDT) for TB? We hypothesize that there is a sex difference in responses to adjunctive HDT because males are more susceptible to TB and various HDTs may have differential, sex-dependent impacts on inflammation. This question is important in the context of ongoing clinical trials that are investigating the potential roles of various HDTs as adjunctive therapy for TB, including the lipid-lowering agents, statins (StAT-TB, NCT03882177), the hypoglycemic agent, metformin (CTRI/2018/01/011176), and the anticancer agent, imatinib (IMPACT-TB, NCT03891901). Data from Pace et al suggested that zileuton is less effective in males, prompting consideration of sex-based differences in leukotriene biosynthesis blockade for respiratory and cardiovascular diseases [3]
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