Background: Although the incidence of infectious diarrhea has declined in HIV+ persons due to the increased use of antiretroviral therapy (ART), HIV- and ART-associated diarrhea affect millions of individuals. Crofelemer is the only drug approved for treatment of diarrhea in HIV+ persons. The ADVENT study responder definition typically required a 90% reduction in watery stools per week. Substantial clinical benefits may occur from a 50% or greater reduction in the frequency of diarrheal symptoms.
Methods: Daily diary data were analyzed retrospectively from all persons treated with crofelemer 125mg bid for up to 20 weeks. The average reduction in watery stools from baseline was determined by week. Chi-square tests were performed to detect differences based on protease inhibitor (PI) use or etiology of diarrhea (ART vs. HIV disease).
Results: The baseline diarrheal frequency was 20 watery stools per week among the 274 enrolled persons. Comparing week 4 to weeks 12 and 20, a 100% reduction in weekly watery stools occurred in 15%, 41%, and 50%, respectively; a 75% reduction occurred in 35%, 60%, and 63%, respectively; a 50% reduction occurred in 48%, 73%, and 73%, respectively (Figure 1). There were no significant differences at any week in the proportion of individuals with ≥50%, ≥75%, and 100% reductions based on PI use or diarrhea etiology.

Figure 1
[Figure 1]

Conclusions: Crofelemer use resulted in marked reductions of watery diarrhea in the majority of persons. Therapeutic regimens now include less use of PIs. Results were similar regardless of whether individuals were taking PIs, and whether the etiology of the diarrhea was believed to be secondary to ART or HIV disease. The utility of crofelemer may have been underestimated based upon the previously reported responder analysis. Given the 36 million people worldwide with HIV, this analysis suggests that millions of HIV-infected persons may achieve clinically meaningful reductions in diarrhea by using crofelemer.

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