Hypersensitivity reactions to HIV therapy

Abstract

Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions.

Selecting patients who can be re-challenged with Nevirapine in case of skin rash with Efavirenz – A Study

“…9,[11][12][13][14] Skin rash with NVP has been documented with an overall incidence of 17-32%, while EFV has a lesser risk (10-27%) on initiating the drug. [14][15][16][17] The incidence of severe rashes with EFV is only 0.1%, compared to 0.3%-1%, as reported with NVP. 11,12,[17][18][19] There are several studies and case reports on the safety of switching of NNRTI in the event of a skin rash.…”

“…[14][15][16][17] The incidence of severe rashes with EFV is only 0.1%, compared to 0.3%-1%, as reported with NVP. 11,12,[17][18][19] There are several studies and case reports on the safety of switching of NNRTI in the event of a skin rash. Mehta and Maartens, in a meta-analysis in 2007, observed that recurrent reactions occurred in 12.6% of patients with rash who were switched from NVP to EFV, compared with 50% of those switched from EFV to NVP.…”

“…Most EFV-induced rashes are mild to moderate with severe rashes (SJS, TEN, EM) reported in only 0·1% of patients, compared with 0·3-1% as reported with NVP. 11,12,[17][18][19] Although female sex and ethnicity are related to the risk of rash with NVP, there is limited data on risk with EFV. 34 Studies by Kiertiburanakul and Sungkanuparph (2009) 35 from Thailand have attributed association of both AIDS-defining illness and high CD4 cell counts at the time of NVP initiation to be associated with NVP-associated rash (Median CD4 cell count at the time of NVP initiation was higher among patients in rash group).…”

All the Postgenomic World is a Stage: The Actors and Narrators Required for Translating Pharmacogenomics into Public Health

“…This serious hypersensitivity occurring in up to 9% of persons receiving abacavir has a strong genetic component associated with the major histocompatibility complex (MHC) allele, HLA-B*5701. The genetic testing for this variant is now recommended in clinical guidelines and is practiced in most Western countries [15]. However, advocating for availability or distribution of, or seeking, HIV therapy in many low-and middle-income countries (LMICs), let alone abacavir genetic testing for its personalized use, may trigger severe, irreversible social consequences.…”

Genetic Factors that Influence HIV Infection: The Role of the Major Histocompatibility Complex System

“…Most of the drugs used to treat HIV infection produce hypersensitivity in a percentage of patients. We recommend to our readers an excellent recent review on the subject (Chaponda et al, 2011). Genetic factors have been shown to play a role in some of the adverse effects of these drugs, especially in the case of abacavir.…”