Dolutegravir-induced colitis in an HIV-infected patient.

Sir, Many of the gastrointestinal (GI) conditions associated with HIV disease have become much less frequent over the past two decades. Diarrhoea from opportunistic infections has become less common, and HIV-associated diarrhoea is now more often due to non-infectious causes such as ART-related adverse events and HIV enteropathy. Diarrhoea associated with ART is most commonly caused by PIs, which may damage the intestinal epithelial barrier and/or alter chloride ion secretion. Less is known about the diarrhoea associated with the other classes of ART. Newer antiretroviral agents offer improvements in potency and activity as well as tolerability. Dolutegravir was approved by the US FDA in August 2013 and is currently recommended as initial treatment in HIV-infected patients, both as part of the fixed-dose combination tablet including abacavir/lamivudine/dolutegravir and separately with tenofovir/emtricitabine. The efficacy of dolutegravir has been demonstrated in several randomized clinical trials (SPRING-1, SPRING-2, SINGLE, FLAMINGO and SAILING). – 7 In a recent safety review of dolutegravir, nausea, diarrhoea and headache were the most commonly reported treatment-related adverse effects. Diarrhoea occurred more often in patients on PI-based therapy (darunavir/ritonavir) than in those on dolutegravir, and the diarrhoea observed with dolutegravir was generally mild in intensity and typically did not prompt discontinuations or changes in treatment. Notably, treatment-emergent diarrhoea of at least moderate intensity occurred in ,1% of patients receiving dolutegravir. We report the case of a woman with chronic HIV infection who, after 18 months of treatment with abacavir/lamivudine and efavirenz, switched to abacavir/lamivudine and dolutegravir to accommodate a new job with a varied schedule including night shifts. The patient’s CD4 cell count was 780 cells/mm and HIV RNA concentration was ,20 copies/mL prior to making the ART change. Her medical history included chronic kidney disease stage 3, hyperlipidaemia, hypothyroidism, osteopenia and allergic rhinitis. Medications aside from ART included alendronate, cholecalciferol, levothyroxine, loratadine, montelukast and pravastatin, all of which she had been taking for at least 2 years. Approximately 3 weeks after the change from efavirenz to dolutegravir, she developed moderate diarrhoea characterized by 6–10 loose watery stools per day associated with urgency and occasional incontinence. She had no fevers or chills and denied any anorexia, nausea, vomiting or abdominal pain. She denied any sick contacts and had not received any recent antimicrobials or other new medications. The results of initial evaluations, including a stool assay for Clostridium difficile and a multiplex PCR test using the FilmArray GI Panel, which detects 22 common viruses, bacteria and parasites that cause infectious diarrhoea, were negative. Pathogens included in the FilmArray GI Panel are as follows: Campylobacter ( jejuni, coli and upsaliensis), Clostridium difficile (toxin A/B), Plesiomonas shigelloides, Salmonella, Yersinia enterocolitica, Vibrio species (including a specific target for Vibrio cholerae), enteroaggregative Escherichia coli, enteropathogenic E. coli, enterotoxigenic E. coli lt/st, Shiga-like toxin-producing E. coli stx1/stx2 (including a specific target for E. coli O157), Shigella/enteroinvasive E. coli, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, sapovirus (I, II, IV and V), Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica and Giardia lamblia. The patient’s symptoms persisted for an additional 2 weeks, so she underwent colonoscopy with biopsy. The colon and terminal Figure 1. Apoptotic cells in the colon (haematoxylin and eosin stain×400). Research letters