A study presented at AIDS 2018 last November showed that the rate of noninfectious, HIV-related diarrhea hasn’t changed significantly over the past nine years — and continues to effect 17 percent of people living with HIV.
The results of this large clinical trial review are highly compelling because chronic HIV-related diarrhea not only has a direct physical effect, but it can also have severe consequences to one’s quality of life, mental well-being, drug effectiveness, and adherence to antiretroviral treatment. Unfortunately, even now, diarrhea is not well addressed as an important health concern in people living with HIV.
Researchers examined data from 38 HIV clinical trials, with a total of 20,000 participants, in studies posted on ClinicalTrials.gov from 2008 to 2017. Selected studies included over 100 participants each and were U.S.-based, though some included sites in additional countries. All studies looked at the efficacy of specific HIV antiretrovirals or ARV regimens, and reported incidences of diarrhea as an adverse event.
Of the 38 trials reviewed, 21 had enrolled participants new to ARV treatment; 11 enrolled participants who had been on treatment for a while and seen their viral loads suppressed to undetectable levels, who then switched to different ARVs; and five enrolled those whose first antiretroviral regimen was failing to fully suppress their HIV (which is often indication of transmitted drug resistance). One study included participants who were both treatment naive and experienced. Participants in the comparative arms were also included in this study.
The point of treatment in those studied (naive, treatment-experienced, or treatment-failures) is important because possible side effects (including diarrhea) after starting new ARVs is somewhat expected. The body often adjusts to new medications so these side effects can ultimately diminish over time. However, long-term noninfectious diarrhea may indicate a different cause such as HIV-enteropathy or may represent a side effect of a specific ARV. In these cases, measures should be taken to diagnose the cause, and treatment or drug changes should be provided where possible.
Researchers found that the rate of diarrhea in the studies reviewed was approximately 17-18 percent and remained consistent over the past nine years, which runs against the common belief that the rates of diarrhea among HIV-positive patients has declined significantly in recent years. This rate was similar in both participants who were taking FDA-approved ARVs and those given experimental therapies. The average reported diarrhea incidence was significantly higher for participants who were treatment-naive versus those who were treatment-experienced at 19.72 percent vs 13.74 percent, respectively.
Researchers also analyzed adverse events reported data from specific ARVs and compared it to corresponding FDA-approved package inserts, and found that the rates of diarrhea reported by drug makers varied greatly from the rates of those in the clinical trials.
For example, the rate reported for Stribild on the package insert was 12 percent, however, the meta-analysis reported 20.6 percent. Similarly for Genvoya, the package insert reported half the rate of the meta-analysis at 7 percent versus 14 percent. For Triumeq, 1 percent (grade 2) versus 16.1 percent; Isentress, none versus 17.2 percent; and Evotaz 11 percent versus 22.1 percent.
This distinction is important since the package inserts report the rates of new or “treatment emergent” incidents of diarrhea attributed to a specific ARV, whereas the clinical trial adverse events (in this case diarrhea) reported in the studies reviewed on ClinicalTrials.gov represent the background rates of diarrhea and highlight the persistence of this important morbidity in the modern era.
“It remains consistent that patients who are living with HIV are still experiencing loose stools and diarrhea irrespective of being on the most current or older antiretroviral regimens. It is also paramount that clinicians not rely solely upon package insert reported rates of adverse events and instead seek the actual occurrence. Any and all efforts undertaken to enhance the quality of life for persons with HIV on antiretrovirals can only hope to improve outcomes, decrease transmissions, and move toward the end of the epidemic,” stated Patrick G. Clay, professor of Pharmacotherapy at the University of North Texas System College of Pharmacy and co-author of the study.
Chronic HIV-related diarrhea is rarely addressed during conversations between people living with HIV and their care providers, and thus can remain untreated. Living with this condition for years can create a sense of acceptance combined with a belief that there’s no point in complaining,