Jason A. Trubiano1,2, Elizabeth J. Phillips3,4
- Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
- Department of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
Adverse drug reactions (ADRs) caused by antiretroviral drugs are an increasingly uncommon complication of contemporary antiretroviral therapy (ART) but are occasionally encountered in clinical practice. Type A ADRs, which are predictable dose-dependent non-immune-mediated reactions (e.g. nausea, vomiting, headache), and drug-drug interactions are predictable and usually manageable. Type B ADRs, which are typically immune-mediated (IgE antibodies or T-cells) hypersensitivity reactions, are less often recognized events that in the setting of an isolated mild to moderate skin rash may be managed with continued treatment (e.g. efavirenz) but in the severest of cases necessitate permanent drug discontinuation and avoidance of all structurally related drugs.1,2
Modern combination ART for HIV infection, in the single tablet regimens that are commonly used, is well tolerated.3 However, drug hypersensitivity reactions may be encountered because people with HIV infection are more susceptible to this problem than the general population, particularly those with uncontrolled HIV viremia.4-6 Despite ADRs caused by antiretroviral drugs being encountered in clinical practice, there is a poor understanding of the mechanisms underlying the increased incidence of these ADRs and the prevalence of immunological phenotypes that increase the risk of an ADR. Data has primarily been extracted from clinical trial data with “real world” post marketing data less frequently reported.7 Determining the true incidence of hypersensitivity reactions to individual antiretroviral drugs is difficult, due to the routine use of combination ART (dual or triple) and the concomitant use of other antimicrobial drugs for prophylaxis or treatment of opportunistic infections in some patients. We will discuss both immune- and non-immune-mediated ADRs associated with commonly employed antiretroviral drugs, as well as immune mediated ADRs to drugs that might be taken concomitantly with antiretroviral drugs.