Background: Despite the perception that gastrointestinal manifestations of HIV infection have declined over time, patients often complain of multiple loose stools per day with significant urgency, bloating, and unwanted disruptions in their quality of life when directly queried. In order to examine whether the rate of HIV-associated diarrhea has changed over time, we interrogated the publicly available NIH database of clinicaltrials.gov that reported the adverse event frequency of diarrhea from 2008-2016.
Methods: Pivotal efficacy intervention trials conducted in the US (including multinational trials) with greater than 100 participants were selected for analysis. Both comparative and switch studies that reported diarrhea as an adverse event were included.
Results: 39 trials met the inclusion criteria with 20,354 trial subjects receiving cART. 12,004 subjects received experimental therapy and 8,350 received the comparator regimen. The weighted average of the prevalence of diarrhea was 17.58% and 18.62% for those receiving experimental versus comparator regimens, respectively. The median prevalence of reported diarrhea was similar at 17.54% and 18.04%, respectively. The linear regression of diarrhea rates by date of completion of the study reveals beta coefficients of -0.0028 and -0.0032 for the experimental drugs versus the comparator regimens, respectively (see graph). These small beta coefficient values, which represent the slope of the line of rates of diarrhea over time, supports the hypothesis that the prevalence of diarrhea in pivotal clinical trials has remained nearly constant over time. The slope of the line does not change if trials with the protease inhibitors best known for increasing GI symptoms are excluded.
Conclusions: The prevalence of diarrhea in ART clinical trials has not declined significantly in the last 10 years. Diarrhea remains a significant comorbidity in HIV-positive patients, even those virally suppressed in clinical trials, with a prevalence of diarrhea of around 18%. These findings emphasize the need for more targeted epidemiologic and interventional studies to characterize the residual morbidity of gastrointestinal disease in people living with HIV as we seek to improve their quality of life and reduce this disruption in their activities of daily living.


[Diarrhea Rates by Date Study Completed]

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