Lymphocytic colitis in an HIV positive patient

Historically, disabling diarrhea was reported in 60–80% of people living with HIV, largely because of infectious pathogens or uncontrolled HIV replication in the gut mucosa [1]. With the widespread use of effective combination antiretroviral therapy, the cause of diarrhea in this population has shifted from primarily infectious causes to drug-induced adverse effects [2]. Many antiretrovirals have been associated with diarrhea, with protease inhibitors being the most common culprit [3]. However, antiretroviral agents are generally not associated with more severe gastrointestinal events, such as drug-induced colitis. Lymphocytic colitis is a type of microscopic colitis that is typically associated with the use of nonsteroidal anti-inflammatory drugs or proton-pump inhibitors [4]. Here, we report a case of lymphocytic colitis that occurred in a patient treated with dolutegravir, lamivudine, and abacavir. A 54-year-old male was diagnosed with HIV-1 in 2018, with a baseline RNA of 80 000 copies/ml and a CD4+ count around 300 cells/mm3. His past medical history was significant for anxiety and depression, managed with lorazepam as needed. On presentation, the patient had been experiencing diarrhea for several weeks. A stool sample was positive for Giardia, and the patient's diarrhea resolved following a 10-day course of metronidazole. He was subsequently initiated on a single-tablet regimen containing dolutegravir 50 mg, lamivudine 300 mg, and abacavir 600 mg after testing confirmed that he was HLA-B5701 negative, and his viral load was suppressed within 3 months. However, within a few days of starting therapy, he began experiencing five to eight watery bowel movements per day associated with urgency. He had no fevers and denied any other symptoms. Investigations for bacteria, parasites and Clostridium difficile were all negative. Postinfectious irritable bowel syndrome was suspected, and the patient was initiated on dairy-free and high-dose fiber diets, with no improvement of his symptoms. The diarrhea continued to persist for months despite trials of rifaximin and pancreatic enzymes and the patient experienced weight loss of approximately 6.8 kg. Approximately 8 months after the onset of symptoms, a colonoscopy was performed to investigate alternative disorders. The colonoscopy revealed lymphocytic colitis, which was deemed to be likely drug-related. His antiretroviral regimen was switched to a regimen of bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg. The patient reported symptom improvement within 2 days, with complete resolution within 1 week after switching regimens along with a 2.3 kg increase in weight within 1 month. His viral load remained undetectable. According to the Naranjo adverse drug reaction probability scale, this patient experienced lymphocytic colitis and diarrhea, which was probably related to his antiretroviral therapy [5]. Symptoms appeared after the suspected drug was administered and persisted despite treatment for alternative causes. The adverse event was confirmed by imaging, and symptoms rapidly disappeared after discontinuation of the medications. One case report of dolutegravir-associated colitis was reported by Bares et al.[6] in 2015. In their report, a female patient was switched from a combination of efavirenz, lamivudine, and abacavir to dolutegravir, lamivudine, and abacavir to improve convenience. She was virally suppressed at the time of the switch and had a CD4+ cell count of 780 cells/μl. Approximately 3 weeks after the medication switch, she developed diarrhea characterized by up to 10 loose watery stools per day that was associated with occasional incontinence but no systemic features. Her diarrhea resolved completely within 2 weeks of stopping dolutegravir and resuming treatment with efavirenz. As the patient remained on lamivudine and abacavir without any issues, it was hypothesized that dolutegravir was the cause of her symptoms. The onset, symptoms, management, and resolution of this published case are strikingly similar to our case. Furthermore, as we did not identify any reports of lymphocytic colitis with nucleoside reverse transcriptase inhibitors or other integrase strand transfer inhibitors, we suspect that dolutegravir was the most likely causative agent of lymphocytic colitis in our patient. Although dolutegravir is generally well tolerated and is associated with moderate-to-severe diarrhea in less than 1% of patients in clinical trials [7], it may be rarely associated with colitis that usually resolves rapidly upon drug discontinuation. Our patient's symptoms completely resolved after switching to bictegravir, suggesting that this may not be a class effect of the integrase inhibitors. Additional case reports are needed to confirm this association. As with all other medications, it is important to report suspected adverse events to the national postmarket drug surveillance program to enhance our knowledge of medication safety profiles. Acknowledgements Conflicts of interest C.M. and S.C. declare no conflicts of interest. A.T. has received speaker and consultant honoraria from Abbvie, Gilead, Merck, and ViiV. S.W. has spoken at CME events, and received consultant fees from Gilead, Merck, Viiv and Jannsen. S.W. holds a chair in HIV clinical management and aging from the Ontario HIV Treatment Network, Canada.

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