Hypersensitivity reactions (HSR) are unexpected, immune (allergy)-like reactions that occur in a minority of patients treated with antiretroviral therapy. No single symptom or laboratory test has been found to predict or diagnose such events. Common symptoms, which appear in combinations, include fever, rash, gastrointestinal reactions, severe fatigue, and respiratory symptoms. Such hypersensitivity reactions constitute a distinct clinical entity and are not the simple rashes (mild rashes without systemic symptoms) that are common reactions to many drugs. Hypersensitivity reactions resolve on discontinuation of the causative drug, but return on reinitiation. The exact mechanism of hypersensitivity reactions is unknown.
Antiretroviral therapy has been demonstrated to be effective in the treatment of individuals infected with Human Immunodeficiency Virus (HIV) or diagnosed with Acquired Immune Deficiency Syndrome (AIDS). Therapy with combinations of antiretroviral agents can prolong survival and decrease the risk of complications of HIV-1 infection. Adverse reactions may occur with any antiretroviral agent, some with the potential to cause severe morbidity and mortality. (See e.g., Samuel et al., Antiretroviral Therapy 2000, Arch. Pharm. Res. 23:425 (2000); Carr et al., Lancet 356:1423 (2000)). Common, and usually less severe, adverse reactions include nausea, headache, fatigue, diarrhea and non-severe skin rashes. Less common but sometimes severe adverse reactions to antiretroviral agents include severe skin rashes, pancreatitis, lactic acidosis, and hypersensitivity reactions.
Hypersensitivity reactions to abacavir (Ziagen) have been reported to occur among approximately 5% of patients who receive this agent alone or in combination with other antiretroviral agents (note that Ziagen is indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents). Discontinuation of abacavir results in resolution of the symptoms of the hypersensitivity reaction. Continued administration of abacavir in the face of an ongoing reaction or reinstitution of abacavir in patients with a prior history of a reaction may result in a sudden, severe, and potentially fatal reaction.
A screening test to identify subjects at increased risk for a hypersensitivity reaction to a pharmaceutical compound would be useful in clinical medicine.
USPTO Backgrounds
USPTO Backgrounds