Immune-mediated drug hypersensitivity reactions are most frequently encountered with nevirapine, efavirenz (both NNRTIs), darunavir (a PI) and abacavir (a NRTI). Despite immune-mediated hypersensitivity reactions occurring at a higher rate in HIV-infected patients than in the general population, pathogenic mechanisms remain largely unknown, though are postulated to result from the interaction of HIV-related, patient (genetic) and …
A significant achievement in the field of HIV medicine has been the discovery of pharmacogenomic predictors of antiretroviral drug hypersensitivity resulting from the interactions between drug and class I and/or class II human leukocyte antigen (HLA) molecules.38 Of these, the association of HLA-B*57:01 with abacavir hypersensitivity is the best recognised and has resulted in the …
Pathogenesis of antiretroviral drug hypersensitivity reactions Read More »
The use of abacavir has been limited by the occurrence of abacavir hypersensitivity syndrome, a distinct entity constituting fever, malaise, respiratory symptoms and gastrointestinal upset. The rash is a late manifestation of the syndrome and occurs in 70% of cases.59 Evidence suggests that most cases present within the first 2–3 weeks of therapy, at a …
Nevirapine has also been associated with immune-mediated hypersensitivity reactions, including DRESS, SJS/TEN and drug-induced liver disease.73 Immune-mediated hypersensitivity is the commonest cause of drug cessation, which occurs in approximately 5% of patients. The pharmacogenomic associations identified for nevirapine hypersensitivity and the spectrum of hypersensitivity syndromes are outlined in Table 2. Nevirapine pharmacogenomic screening HLA associations …
DRESS has been reported with raltegravir therapy and case reports to-date have underscored the pre-disposition of individuals of African ancestry. In keeping with this, an association of HLA-B*53:01, an allele prevalent in those of African ancestry, with raltegravir associated DRESS has been reported by Thomas et al.35, who demonstrated that 5 of the 6 patients …
Diagnosis Skin prick and intradermal testing with the drug under investigation, followed by a confirmatory oral provocation test, has been the gold standard for identification of drugs associated with immediate hypersensitivity reactions to antibiotics.82,83 For antiretroviral drug hypersensitivity reactions, the majority of cutaneous reactions are delayed and drugs are primarily available as oral preparations and …
Approach to assessing antiretroviral drug hypersensitivity Read More »
Table 1: Most frequent non-immune mediated adverse reactions reported to currently utilized antiretroviral drug Drug Gastrointestinal Neurological Renal (biochemical) Renal (obstructive) Metabolic Musculoskeletal Hepatic Respiratory Cutaneous (non-rash) Nucleoside reverse transcriptase inhibitors (NRTI) Abacavir + – + – ++^ – – – – Lamivudine + + ° – – +^ – + – – Emtricitabine ++ …
Phillips EJ. Classifying ADRs – does dose matter? Br J Clin Pharmacol. 2016; 81:10-2. Drug hypersensitivity. Pichler WJ (ed), Karger, Basel, 2007. Nuesch R, Srasuebkul P, Ananworanich J, et al. Monitoring the toxicity of antiretroviral therapy in resource limited settings: a prospective clinical trial cohort in Thailand. J Antimicrob Chemother. 2006; 58:637-44. Pirmohamed M, Park BK. …
Alison Duncan1 and Dianne Carey2 Pharmacy Department, The Alfred Hospital, Melbourne, VIC 3004 The Kirby Institute, UNSW Sydney, NSW 2052 Last reviewed: November 2019 Overview Drug-drug interactions between antiretroviral (ARV) drugs and co-prescribed medication are common and may lead to an increase or decrease in exposure to either drug. These alterations in exposure may result …
Drug-drug interactions in patients with HIV infection Read More »
Drug-drug interactions can be either pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions are the primary concern with ARV drugs. Pharmacokinetic interactions occur when one drug alters the absorption, distribution, metabolism or excretion of another drug, possibly increasing or decreasing its plasma concentration. For ARV drugs the interaction types of concern are absorption, metabolism and excretion. …