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, combined effect 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 antiretroviral treatment. Antiretroviral treatment can lead to improvements in gastrointestinal symptoms for patients with advanced immunosuppression. This was observed in the TORO trials of
enfuvirtide and the DUET trials of
etravirine, which were conducted in highly treatment experienced patients with low baseline CD4 counts. While antiretroviral treatment can improve immune function, leading to fewer gastrointestinal symptoms, this could be counter-balanced by adverse gastrointestinal toxicity profiles from certain antiretrovirals.
Ritonavir-boosted
protease inhibitors show a range of gastrointestinal side effects; there are differences in tolerability within this class of antiretrovirals, influenced both by the dose of
ritonavir used 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 a well-characterized problem of
nausea. Issues relating to gastrointestinal complications are often subjective, reliant upon patient reporting and perception, along with clinician interaction and intervention. In trial publications, many different systems are used to present gastrointestinal adverse events. Most are based on the US Division of
AIDS Grading Scale, ranging from grade 1 (mild) to grade 4 (life-threatening). Clinical trials most commonly report grade 2-4 gastrointestinal adverse events, which are at least possibly related to study medication. In future, it is important for clinical trials to report gastrointestinal adverse events in a consistent way. The percentage of patients with
drug-related grade 2-4 events should be reported. In addition, the percentage with any grade 2-4 gastrointestinal adverse event should be included, since there could be subjectivity in the assessment of
drug relatedness in open-label clinical trials. The percentage of patients who use medications to lessen the symptoms of
diarrhea and other gastrointestinal adverse events should also be reported.