Adverse reactions to antiretroviral and other drugs in people with HIV infection

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. Introduction Adverse drug reactions (ADRs) …

Adverse reactions to antiretroviral and other drugs in people with HIV infection Read More »

Type A ADRs are most commonly encountered with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), with hepatic and renal impairment the most commonly reported reactions.8 In the modern era, most cases of renal impairment are attributable to the use of tenofovir disoproxil fumarate (TDF). In contrast, gastrointestinal symptoms occur most often in the setting of protease inhibitor …

Non-immune mediated adverse drug reactions Read More »

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 …

Immune-mediated drug hypersensitivity reactions Read More »

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 …

Abacavir hypersensitivity syndrome Read More »

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 …

Nevirapine hypersensitivity reactions Read More »

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 …

Raltegravir hypersensitivity reactions Read More »

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 ++ …

Tables and Figures Read More »

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. …

References Read More »