Use of dupilumab in patients who are HIV‐positive: report of four cases

Dear Editor, Atopic dermatitis (AD) and prurigo nodularis (PN) are defined by the drive to itch. Indeed, AD is so intensely pruritic, it is described as the itch that rashes. Incidences of AD and PN are higher in patients with HIV, with a prevalence of 30–50% in patients who are HIV‐positive, in contrast to a prevalence of 2–5% in seronegative adults.1 Additionally, approximately 39% of patients with HIV have PN, supporting PN as the most frequent skin disorder in patients who are HIV‐positive.1 Dupilumab, a novel monoclonal interleukin (IL)‐4/IL‐13 antagonist, is the first biologic approved for the treatment of moderate‐to‐severe AD. Recent reports have described that dupilumab provides improvement in patients with PN.2 Unfortunately, the effects of dupilumab in patients who are HIV‐positive are unknown, as these patients were excluded from clinical trials. Herein, we describe four patients with HIV, two with concomitant AD and two with concomitant PN, that were treated safely and successfully with dupilumab. All patients reported an improvement in the severity of itch as measured by the numerical rating scale for itch intensity (NRSi). Clinical improvement was noted for all patients as measured by the Investigator's Global Assessment (IGA). NRSi, IGA and HIV laboratory values are summarized in Table 1. HIV disease activity during treatment with dupilumab IGA, Investigator's Global Assessment; NRSi, numerical rating scale for itch intensity. HIV disease activity during treatment with dupilumab IGA, Investigator's Global Assessment; NRSi, numerical rating scale for itch intensity. Superpotent topical steroids and topical calcineurin inhibitors failed to provide benefit in all patients. Narrowband ultraviolet B failed in patients with schedules that allowed for regular phototherapy sessions. Treatment with dupilumab was initiated using standard dosing regimen of a 600‐mg induction dose followed by 300 mg every 2 weeks. No adverse events were reported. Patient 1 was a man in his 60s with severe PN. The pre‐dupilumab viral load was 168 copies mL–1, the absolute CD4 count was 229 cells μL–1 and the CD4/CD8 ratio was 0.16. An initial NRSi of 7/10 was reported by the patient. After 2 weeks of dupilumab, NRSi improved to 4/10. At 1‐, 4‐, 6‐ and 9‐month follow‐ups the patient reported an NRSi of 0/10. Stepwise clinical improvement was noted with dupilumab. Patient 2 was a man in his 60s with severe PN. The pre‐dupilumab viral load was undetectable, the absolute CD4 count was 1058 cells μL–1 and the CD4/CD8 ratio was 0.77. With an initial patient reported NRSi of 10/10, this patient desired more aggressive treatment but also wanted to avoid all frankly immunosuppressive medications, such as prednisone, despite well‐controlled HIV. At 1‐month follow‐up, the patient‐reported NRSi improved to 5/10. At 2‐, 3‐ and 6‐month follow‐ups the NRSi was 0/10. Patient 3 was a woman in her 20s with severe AD. Pre‐dupilumab, the viral load was undetectable, the absolute CD4 count was 860 cells μL–1 and the CD4/CD8 ratio was 2.1. At 2‐ and 4‐month follow‐ups, the patient reported an NRSi of 0/10. Patient 4 was a woman in her 40s with severe AD. As a result of poorly controlled HIV disease, topicals and narrowband ultraviolet B were attempted for an extended period. After failure to improve and the patient's desire for aggressive therapy, dupilumab was initiated. The pre‐dupilumab viral load was 276 k, the absolute CD4 count was 77 cells μL–1 and the CD4/CD8 ratio was 0.06. The initial patient‐reported NRSi was 10/10. At the 2‐week follow‐up, AD disease was still severe, but the patient reported an improved NRSi of 7/10. At the 6‐week and 4‐month follow‐ups, the patient reported an NRSi of 2/10. Our patients experienced rapid and substantial improvements in itch severity while HIV laboratory values remained stable, despite great variance in the degree of HIV disease control. However, laboratory values must be interpreted carefully in the context of accurately reflecting the presence of clinically significant improvements in HIV disease, as count fluctuations in both healthy individuals and those who are HIV‐positive are normal.3 Despite interpersonal variations, a change of at least 30% between two absolute CD4 count‐test results for a patient on antiretroviral therapy is considered to be significant,4 which we did not see. Given the number of patients and the relatively brief follow‐up time, we would like to emphasize that the laboratory values do not provide quantitative evidence on the safety of dupilumab in patients who are HIV‐positive. That dupilumab did not patently exacerbate our patients’ underlying immunodeficiency is not surprising. A T helper (Th)1/Th2 imbalance is also seen in most patients with HIV, with evidence for increased Th2 responses.5 Additionally, HIV‐1‐glycoprotein‐120 is a potent stimulator of IL‐4, and indirectly increases virulence.6 In both Europe and Nairobi, human resistance to HIV infection has been noted in cohorts with IL‐4 genetic variations resulting in a net decrease of IL‐4 activity.7,8 All suggest that inhibition of IL‐4 may be beneficial in the setting of HIV infection. The marked NRSi and IGA improvements in our patients are promising. Firstly, we recapitulate that dupilumab provides rapid and substantial improvement in both AD and PN. Secondly, the cases of these patients provide preliminary evidence that dupilumab is safe in patients who are HIV‐positive and does not instigate disease progression. Our findings point to the necessity for further studies to address this unmet need. Funding sources: none. Conflicts of interest: N.K.M. and S.H. report serving as investigators in trials sponsored by Sanofi and Regeneron Pharmaceuticals.