HIV Patients with Trimethoprim-sulfamethoxazole Intolerance May Tolerate Dapsone

A recent study published online in the Journal of Allergy and Clinical Immunology: In Practice has shown that patients with HIV who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX) may tolerate dapsone.

According to Sara M. May, MD, from the University of Nebraska Medical Center, Omaha, and colleagues, “[t]he drug of choice for the treatment and prevention of Pneumocystis jiroveci pneumonia is trimethoprim-sulfamethoxazole.” For patients who cannot tolerate TMP-SMX, but require prophylaxis for Pneumocystis jiroveci pneumonia, they stress that dapsone is the best choice of therapy among the alternative options.

“This study demonstrates that HIV patients with trimethoprim-sulfamethoxazole intolerance may tolerate dapsone,” the authors add.

Although the sulfonamide antibiotic TMP-SMX has been the cornerstone of treatment of Pneumocystis jiroveci pneumonia, many patients with HIV experience hypersensitivity to the drug. One alternative therapy is the sulfone antimicrobial dapsone. But because both contain a sulfa moiety, cross-reactivity between the medications could potentially occur. HIV patients who experience hypersensitivity reactions to TMP-SMX may therefore also react in the same way to dapsone therapy.

However, studies to investigate this cross-reactivity are lacking and have produced conflicting results. With this in mind, Dr. May and colleagues performed a retrospective chart review among HIV patients, to assess the probability of dapsone hypersensitivity in those who were intolerant of TMP-SMX.

Among a total of 1,684 HIV patients, 60 (12.2%) had reported hypersensitivity to sulfonamide antibiotics: of these 60 individuals, 72% of had experienced cutaneous reactions, and 10% had experienced serious systemic reactions.

Of these patients with sulfonamide intolerance, 10% had reported intolerance to dapsone. This intolerance resulted in cutaneous reactions in 50% of the patients, and in hematological reactions in 33%.

According to the authors, 13 (21.7%) of the 60 patients received dapsone and all tolerated the drug, showing that HIV patients with a history of TMP-SMX intolerance may be able to tolerate dapsone therapy. One of these patients even experienced exfoliative dermatitis as a reaction to TMP-SMX and still tolerated dapsone, they add. In addition, more than half of these 13 patients also experienced other drug intolerances.

They note that none of the 13 patients with sulfonamide intolerance had an adverse drug reaction after they received dapsone therapy. Although the authors suggest that a trial in dapsone therapy could be considered in HIV patients with a history of TMP-SMX intolerance, they stress that patients with severe drug hypersensitivity reactions to TMP-SMX should still continue to avoid dapsone.

According to Dr. May and colleagues, studies have produced conflicting results about the level of cross-reactivity between TMP-SMX and dapsone in HIV patients. Although some studies have reported high rates of cross-reactivity, others have shown lower rates (12% to 17%), like what Dr. May and colleagues found in this study.

“This tolerance of dapsone may be related to low cross-reactivity, but also might be due to partial or complete loss of sensitivity to sulfonamide antibiotics with time. This may also be the reason for variation in reported cross-reactivity rates in the literature,” the authors conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.