Increased Adverse Drug Reactions to Antimicrobials and Anticonvulsants in Patients with HIV Infection

Lin, Daren; Tucker, M. J.; Rieder, Michael J.

doi:10.1345/aph.1g525

Cited by 36 publications

(21 citation statements)

References 98 publications

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“…Epidemiology suggests that only around 3% of SMX-treated individuals develop allergy upon drug exposure [64]. However, during the early years of the HIV epidemic, when patients with HIV infection and T cell immunodeficiency received SMX/trimethoprim (SMX/TMP) as a prophylaxis against opportunistic infections, cutaneous, allergy-like side effects to SMX/TMP occurred in 30-50% of treated HIV-positive patients [65,66]. ‘Sulfa-allergy' is also more prevalent in patients with active autoimmune disease [67].…”

Section: Requirements For Costimulation For P-i Stimulationsmentioning

confidence: 99%

Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors

Pichler

Adam

Watkins

et al. 2015

Int Arch Allergy Immunol

157

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Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called ‘off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the ‘pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from ‘conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions.

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Section: Requirements For Costimulation For P-i Stimulationsmentioning

confidence: 99%

Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors

Pichler

Adam

Watkins

et al. 2015

Int Arch Allergy Immunol

157

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“…There is a marked increase in risk for ADRs among people with HIV infection and AIDS compared to both uninfected people and to people with other causes of immunodeficiency such as cancer or primary immunodeficiency [22]. While the reasons for this are unclear, this increase in risk for ADRs appears to be very specific for HIV infection and apply to a broad range of drugs [23]. As well, the risk for ADRs is primarily for hypersensitivity ADRs as opposed to concentrationdependent ADRs, for which the risk appears to be the same for people infected with HIV as for patients with other reasons for immunodeficiency [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…While the reasons for this are unclear, this increase in risk for ADRs appears to be very specific for HIV infection and apply to a broad range of drugs [23]. As well, the risk for ADRs is primarily for hypersensitivity ADRs as opposed to concentrationdependent ADRs, for which the risk appears to be the same for people infected with HIV as for patients with other reasons for immunodeficiency [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

et al. 2009

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HIV infection results in severe immune dysfunction with ensuing sequelae that includes characteristic opportunistic infections. Pneumocystis pneumonia (PCP) is one of the most common of these infections and is routinely treated with sulphamethaxazole (SMX). Although this drug is known to cause hypersensitivity adverse drug reactions (ADRs) in 0.1% of the general population, the incidence of these ADRs increases tenfold in the HIV-positive population. The HIV-1 trans-activator of transcription (HIV-1 Tat) together with the drug metabolite sulphamethaxazole-hydroxylamine (SMX-HA) have both been reported to be factors in these hypersensitivity ADRs. In this study, we use an inducible, Tat-expressing vector system to show that the level of Tat expression contributes to the cellular sensitivity of Jurkat T cells to SMX-HA. We further demonstrated that apoptosis is the likely mechanism by which this occurs. Thus, our data provide insight into the significant increase of SMX-related ADRs during the transition between HIV-1 infection and AIDS.

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“…Didanosine (ddI) and zalcitabine (ddC) may cause painful oral ulcers. Other side eff ects of medicati ons commonly used in the treatment of HIV, such as anaemia, thrombocytopenia, and neutropenia may be manifested in the oral cavity through bleeding or infecti on [20][21][22] . The sweetners used in pediatric syrups contribute to development of dental caries.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Oral Health Status as an Indicator of Disease Progression in HIV Positive Children

Damle¹,

Jetpurwala²,

Saini³

et al. 2010

Pesq Bras Odontoped Clin Integr

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RESUMO ABSTRACT DESCRITORESHIV; Contagem de linfócito CD4; Síndrome de Imunodefi ciência Adquirida; Saúde bucal. KEYWORDSHIV; CD4 Lymphocyte count; Acquired Immunodefi ciency Syndrome; Oral health. ISSN -1519-0501 DOI: 10.4034/1519.0501.2010 Objecti ve: To evaluate the oral health status i.e., gingival conditi on, dental caries, oral mucosal lesions progression in a group of HIV positi ve children in relati on to CD4 count. Method: A total of 234 HIV positi ve children in the age group of 2-15 years were included in the present study. Dental caries status was evaluated as per the criteria devised by WHO. Gingival conditi on index was used to assess and criteria given by Muhlemann was used for Papillary Bleeding scores. Plaque was assessed using the Sillness and Loe Index. The children were under acti ve anti retroviral therapy the CD4 count of each pati ent was available from the hospital records. Results: Maximum dmft /defs, score was observed in individuals with CD4 count 200 -500. Whereas highest mean DMFT/DMFS score was seen in children with CD4 count less than 200. The mean plaque, gingival and papillary bleeding score were highest in individuals with CD4 count less than 200 but the diff erence was stati sti cally insignifi cant. Pseudomembranous candidiasis was the most observed oral lesion. Tongue was the most common site of occurrence of oral lesions in all groups. Conclusion:The study confi rms that the oral health status in HIV positi ve children deteriorates with the decline in CD4 count.

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Increased Adverse Drug Reactions to Antimicrobials and Anticonvulsants in Patients with HIV Infection

Abstract: ADRs to antimicrobial and anticonvulsant therapy cause markedly increased morbidity and mortality in HIV-positive patients. Further research involving the interaction between HIV and the increased ADRs to these drugs is required.

Cited by 36 publications

References 98 publications

Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors

Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors

HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

Evaluation of Oral Health Status as an Indicator of Disease Progression in HIV Positive Children

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