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Gene Screening Lowers Rate of Abacavir Reaction
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8th International Congress on Drug Therapy in HIV Infection
November 12-16, 2006
Glasgow, Scotland
Mark Mascolini
Routinely screening patients for a genetic marker (HLA-B*5701) linked to the abacavir hypersensitivity reaction lowered the rate of that side effect in the large HIV clinic at London's Chelsea and Westminster Hospital [1].
After the hospital began regular HLA screening in August 2005, Laura Waters and colleagues ordered 739 HLA-B*5701 tests, only 4 of which failed. Of the 735 successful tests, 54 (7.3%) registered positive results, including 11 of 111 assays (9.9%) in females and 46 of 642 (6.9%) in males, a nonsignificant gender difference (P = 0.35).
A surprisingly high proportion of positive tests came from black patients (Table 1). As the University of Perth's Simon Mallal reported just before Waters' talk, HLA-B*5701 prevalence in Africa is thought to be around 1%. Supporting Waters' findings, a report from St. Mary's Hospital in London found HLA-B*5701 in 8 of 117 blacks (6.8%) [2]. But a study of 39 African and Antillean blacks in France turned up no positive tests for this genetic marker [3].
Among 54 people with a positive HLA test at Chelsea and Westminster, 25 had not tried antiretroviral therapy; 14 of those 25 did not begin treatment during follow-up, 9 began a nonabacavir regimen, and 2 began abacavir. Both people who started abacavir had a hypersensitivity reaction. Among 29 people with antiretroviral experience before a positive HLA test, none later began abacavir. Seven, though, had tried abacavir earlier, and 4 of them had symptoms of hypersensitivity. Two of those 4 tolerated abacavir (for 6 weeks and 5 years of follow-up).
Of the 681 people with a negative HLA test, 285 had not taken antiretrovirals at the time of the test, 163 of whom remain naive. Of the 47 HLA-B*5701-negative people who began an abacavir-containing regimen, none had to stop the drug because of hypersensitivity or any other reason. Among 396 treatment-experienced people with a negative test, 151 switched to abacavir during follow-up and 8 of them later stopped the drug, 4 (2.6%) because of suspected hypersensitivity.
Before Chelsea and Westminster began screening for HLA-B*5701, 10 of 134 people starting abacavir (7.5%) had a suspected hypersensitivity reaction. After screening began, 6 of 201 people starting abacavir (3.0%) had a reaction, a difference that stopped short of statistical significance (P = 0.10)--but clearly a clinically significant advantage for people who avoided the reaction because of testing. Waters cautioned that the 4 hypersensitivity reactions in people with a negative HLA test highlight the importance of clinical vigilance whenever beginning abacavir therapy.
References
1. Waters L, Gritz A, Maitland D, Nelson M. HLA-B5701 testing and abacavir hypersensitivity: a single centre experience. 8th International Congress on Drug Therapy in HIV Infection, November 12-16, 2006, Glasgow. Abstract PL9.2.
2. Collister C, Marret B, Portsmouth S, et al. HLA-B*5701 carriage frequency in a London cohort will prospective screening be of use in our population? 8th International Congress on Drug Therapy in HIV Infection, November 12-16, 2006, Glasgow. Abstract P82.
3. Zucman D, De Truchis P, Majerholc C, et al. Screening for HLA-B5701 in a population of HIV patients of diverse ethnic origin exposed to abacavir in France. 8th International Congress on Drug Therapy in HIV Infection, November 12-16, 2006, Glasgow. Abstract P116.
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