Investigating Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) reported in association with HIV antiretroviral therapy: An analysis of the FDA Adverse Event Reporting System

Abstract

Antiretroviral medications used to treat and prevent human immunodeficiency virus (HIV) are the cornerstone in management and should be initiated as early as possible.¹ These medications are widely regarded as efficacious, with benefits outweighing potential risks and contributing to longer, healthier lives for patients. Previous literature has described nevirapine and raltegravir, two commonly prescribed medications, as associated with the development of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS);^{2, 3} however, little is known regarding reports of cutaneous drug eruptions among other antiretrovirals. This study seeks to provide a classification of reported events of DRESS in relation to the use of antiretrovirals for HIV prevention and treatment.

The FDA Adverse Event Reporting System (FAERS) Public Dashboard was used to extract all available data through 31 December 2023 for the analysis of reports of DRESS in relation to 40 different HIV antiretroviral medications. These medications were categorized into seven groups: combination antiretrovirals (cARTs), nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), entry inhibitors (EIs), protease inhibitors (PIs), integrase inhibitors (INSTIs), and boosting agents (BAs). A full description of each medication included can be found in Table 1. To ensure broad data collection, both brand and generic names were included for each unique medication. The frequencies of both DRESS and total cutaneous-specific adverse events were recorded in Figure 1.

Among the 40 unique antiretroviral medications analysed, there were 30,353 cutaneous-specific adverse events. Among these, 1295 (4.3%) were cases of DRESS. Six relatively new medications (with brand name—drug class) that had no reported cases at the time of data collection were as follows: dolutegravir/lamivudine (Dovato—cART), doravirine/lamivudine/tenofovir disoproxil (Delstrigo—cART), darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza—cART), atazanavir/cobicistat (Evotaz—PI), nelfinavir (Viracept—PI), and ibalizumab-uiyk (Trogarzo—EI). Individual antiretrovirals most reported in association with DRESS were raltegravir (Isentriss—INSTI) (15.0% of DRESS cases, n = 194), ritonavir (Norvir—BA) (10.5%, n = 136), atazanavir (Reyataz—PI) (10.2%, n = 132), lopinavir/ritonavir (Kaletra—PI) (8.3%, n = 107), and emtricitabine/tenofovir (Truvada—cART) (7.8%, n = 101). Nevirapine (Viramune—NNRTI) had 71 reported cases (5.5%). Among medication classes, the most reported in association with DRESS was PI (27.8%, n = 359), followed by cART (20.3%, n = 263) and NRTIs (12.4%, n = 160). The newest class of antiretroviral therapy, the EIs, was the lowest reported class, with 10 total cases at the time of data collection.

This study provides a collection of reported cases of DRESS associated with antiretrovirals used in HIV prevention and treatment. Notably, antiretrovirals most reported in association with DRESS have been on the market for a longer span of time. However, every drug class has been implicated in causing this cutaneous drug reaction. PIs were the most frequently reported drug class, although raltegravir (INSTI) was the most commonly reported medication overall. This study is limited due to the nature of freely reported, unverified data on FAERS, including diagnoses by nondermatologists and varying availability periods for each drug.⁴ Current understanding of DRESS suggests multifactorial involvement;⁵ thus, this study highlights the need for further research to determine any potential pharmacopathologic mechanisms. Additionally, continued long-term surveillance is essential to further evaluate potential cutaneous adverse events, especially among newer agents. Nonetheless, this study is a valuable collection of high-level data upon which practitioners caring for patients using these antiretrovirals can consider counselling.

Bianca E. Ituarte: Conceptualization; methodology; formal analysis; data curation; writing—original draft. Mitchell A. Taylor: Formal analysis; data curation; writing—original draft. Erin X. Wei: Writing—review and editing; visualization. Jennifer Adams: Conceptualization; writing—review and editing; visualization; supervision.

The authors declare no conflicts of interest.

Not applicable.