Drug hypersensitivity in HIV infection

Abstract

Purpose of review-Immune-mediated adverse drug reactions (IM-ADRs) are many times more common in HIV-infected patients. Usual offending drugs include antiretroviral and antiinfectives, but the burden of specific drug IM-ADRs is population-specific; changing as new and fixed dose combinations enter the market, and drug-resistance patterns demand. This review considers recent literature on epidemiology, mechanisms, clinical management and prevention of IM-ADRs amongst persons living with HIV/AIDS. Recent findings-Epidemiological studies continue to describe high rates of delayed hypersensitivity to known offenders, as well as similar reactions in preexposure prophylaxis. IM-ADRs to oral and injectable integrase strand transfer inhibitors are reported with expanding use. The clinical spectrum and management of IM-ADRs occurring in HIV-infected populations is similar to uninfected; with exceptions such as a recently described severe delayed efavirenz DILI with high mortality. Furthermore, the context can be unique, such as the lower than expected mortality in a Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) cohort from a HIV/TB high burden setting. Programmatic data showing the near complete elimination of Abacavir drug hypersensitivity syndrome following implementation of HLA-B57:01 screening is a stellar example of how prevention is possible with mechanistic insight. Summary-IM-ADRs remain a challenge in persons living with HIV. The complexities posed by polypharmacy, overlapping drug toxicities, drug interactions, overlap of IM-ADRs with other diseases, limited alternative drugs, and vulnerable patients with advanced immunosuppression with high mortality, necessitate increased use of drug provocation testing, treat-through and desensitization strategies. There is an urgent need for improved diagnostics and predictive biomarkers for prevention, or to guide treat-through, rechallenge and desensitization approaches.

A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime?

“…In this instance, it is not to be discounted that a rare side effect, such as TEN, occurring with a not commonly associated drug, hydroxychloroquine, could have been favored by the particular immune stimulation induced by the virus SARS-CoV-2 [ 3 ]. SJS/TEN, and SCAR more generally, have been classically demonstrated to be associated with viral replication [ 11 , 32 – 34 ].…”

SJS/TEN 2019: From science to translation

“…SJS/TEN in children is more frequently non-drug related; with SJS/TEN very uncommon in the very young (< 2 years old) [36]. SJS/TEN is considerably more common (up to 150-fold) in certain immunocompromized patient populations, such as patients with cancer and HIV/AIDS [37]. Newer immunomodulatory treatments such as the immune checkpoint inhibitors used for treatment of previously untreated cancers such as melanoma have been transformative but have been associated with severe and unpredictable adverse events.…”

“…Since SJS/TEN has been reported several months after the administration of these agents a high index of suspicion needs to be maintained. SJS/TEN mortality is higher in the elderly with malignant co-morbidity (>50%) and pre-existing hepatic disease [37][38][39].…”

HIV infection confers distinct mechanisms in severe drug eruption: Endogenous virus activation with aberrant Th2/Th1 and CD8+ T cells function

“…6 This increased susceptibility may be related to the administration of multiple drugs or immune dysfunction. 7 Considering the immune disorders, SDE pathogenesis in HIV/ AIDS patients becomes distinct and intricate. Therefore, it is important to fully investigative the potential immune mechanisms underlying SDE in HIV-infected patients.…”