Risk Factors for Gastrointestinal Adverse Events in HIV Treated and Untreated Patients

Advanced immunosuppression from HIV infection can lead to gastrointestinal symptoms such as diarrhea,nausea, vomiting, dysphagia, weight loss, and abdominal pain. There is a complex, combinedeffect of HIV infection plus antiretroviral treatment on the incidence of gastrointestinal symptoms, and,for some trials, the majority of gastrointestinal adverse events may not be related to antiretroviraltreatment. Antiretroviral treatment can lead to improvements in gastrointestinal symptoms for patientswith advanced immunosuppression. This was observed in the TORO trials of enfuvirtide and the DUETtrials of etravirine, which were conducted in highly treatment experienced patients with low baselineCD4 counts.While antiretroviral treatment can improve immune function, leading to fewer gastrointestinalsymptoms, this could be counter-balanced by adverse gastrointestinal toxicity profiles from certainantiretrovirals. Ritonavir-boosted protease inhibitors show a range of gastrointestinal side effects; thereare differences in tolerability within this class of antiretrovirals, influenced both by the dose of ritonavirused and the choice of boosted protease inhibitor. Overall, lopinavir/ritonavir and fosamprenavir/ritonavir tend to show the highest rates of drug-related grade 2-4 diarrhea, compared with atazanavir/ritonavir, darunavir/ritonavir, or saquinavir/ritonavir. Of the nucleoside analogs, zidovudine leads to awell-characterized problem of nausea.Issues relating to gastrointestinal complications are often subjective, reliant upon patient reportingand perception, along with clinician interaction and intervention. In trial publications, many differentsystems are used to present gastrointestinal adverse events. Most are based on the US Division ofAIDS Grading Scale, ranging from grade 1 (mild) to grade 4 (life-threatening). Clinical trials mostcommonly report grade 2-4 gastrointestinal adverse events, which are at least possibly related to studymedication. In future, it is important for clinical trials to report gastrointestinal adverse events in aconsistent way. The percentage of patients with drug-related grade 2-4 events should be reported. Inaddition, the percentage with any grade 2-4 gastrointestinal adverse event should be included, sincethere could be subjectivity in the assessment of drug relatedness in open-label clinical trials. Thepercentage of patients who use medications to lessen the symptoms of diarrhea and other gastrointestinaladverse events should also be reported.