Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA
pharmacogenetic substudy of DART.
Author(s): Munderi P, Snowden WB, Walker AS, Kityo C, Mosteller M, Kabuye G, Thoofer NK,
Ssali F, Gilks CF, Hughes AR; DART Trial Team.
Collaborators: Grosskurth H, Munderi P, Kabuye G, Nsibambi D, Kasirye R, Zalwango
E, Nakazibwe M, Kikaire B, Nassuna G, Massa R, Fadhiru K, Namyalo M, Zalwango A,
Generous L, Khauka P, Rutikarayo N, Nakahima W, Mugisha A, Todd J, Levin J,
Muyingo S, Ruberantwari A, Kaleebu P, Yirrell D, Ndembi N, Lyagoba F, Hughes P,
Aber M, Medina Lara A, Foster S, Amurwon J, Nyanzi Wakholi B, Mugyenyi P, Kityo
C, Ssali F, Tumukunde D, Otim T, Kabanda J, Musana H, Akao J, Kyomugisha H,
Byamukama A, Sabiiti J, Komugyena J, Wavamunno P, Mukiibi S, Drasiku A,
Byaruhanga R, Labeja O, Katundu P, Tugume S, Awio P, Namazzi A, Bakeinyaga GT,
Katabira H, Abaine D, Tukamushaba J, Anywar W, Ojiambo W, Angweng E, Murungi S,
Haguma W, Atwiine S, Kigozi J, Ochai R, Muhweezi D, Gilks C, Boocock K,
Puddephatt C, Winogron D, Bohannon J, Darbyshire J, Gibb DM, Burke A, Bray D,
Babiker A, Walker AS, Wilkes H, Rauchenberger M, Sheehan S, Peto L, Taylor K,
Spyer M, Ferrier A, Naidoo B, Dunn D, Goodall R, Weller I, Babiker A, Bahendeka
S, Bassett M, Chogo Wapakhabulo A, Darbyshire J, Gazzard B, Gilks C, Grosskurth
H, Hakim J, Latif A, Mapuchere C, Mugurungi O, Mugyenyi P, Burke C, Distel M,
Jones S, Loeliger E, Naidoo P, Newland C, Pearce G, Rahim S, Rooney J, Smith M,
Snowden W, Steens JM, Breckenridge A, McLaren A, Hill C, Matenga J, Pozniak A,
Serwadda D.
Affiliation(s): MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
Publication date & source: 2011, Trop Med Int Health. , 16(2):200-4
OBJECTIVES: To determine the frequencies of HLA-B alleles in Ugandan patients in
the NORA substudy of the DART trial and to compare HLA-B allele frequencies in
those with and without clinically diagnosed hypersensitivity reaction (HSR).
METHODS: DNA-based HLA-B genotyping was used to determine HLA alleles in 247
participants who received abacavir, including all six participants ('cases') with
clinically diagnosed abacavir HSR.
RESULTS: The incidence of clinical abacavir HSR in this double-blinded study was
2.0% (6/300) in the abacavir group. As HLA-B*5701 was absent throughout the
entire cohort, including the six HSR 'cases', an association could not be
established between HLA-B*5701 and clinically diagnosed abacavir HSR. No other
HLA-B*57 alleles were present among the six 'cases'. HLA-B*5703 was the most
frequent HLA-B*57 allele among the abacavir-tolerant participants.
CONCLUSION: The rate of clinical HSR was low, which may reflect the expected 2-3%
clinical false-positive rate seen in previous double-blind randomized studies.
The presumption that these cases may be false-positive abacavir HSR is supported
by the fact that no HLA-B*5701 alleles were found in the abacavir group.
Implementation of prospective HLA-B*5701 screening must be based on benefit/risk
considerations within local practice. Clinical risk management remains paramount.
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