PMID- 31277607 OWN - NLM STAT- MEDLINE DCOM- 20190923 LR - 20200225 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 19 IP - 1 DP - 2019 Jul 5 TI - Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: a meta-analysis. PG - 583 LID - 10.1186/s12879-019-4227-5 [doi] LID - 583 AB - BACKGROUND: Human leukocyte antigen (HLA) alleles are implicated in drug-induced hypersensitivity, including by nevirapine and abacavir. The purpose of this meta-analysis was to evaluate the relationship between HLA polymorphisms and hypersensitivity to antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients. METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library for studies that evaluated the associations of HLA polymorphisms with antiretroviral therapy-induced hypersensitivity published in April 2019. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were considered as estimates of the effect. RESULTS: The meta-analysis included 17 studies that assessed a total of 4273 patients. First, carriers of HLA-A *24 were associated with an increased risk of hypersensitivity among patients with HIV who received antiretroviral therapy (OR: 12.12; P = 0.018). Second, five SNPs of HLA-B genotypes, including *18 (OR: 1.63; P = 0.028), *35 (OR: 2.31; P = 0.002), *39 (OR: 11.85; P = 0.040), *51 (OR: 1.66; P = 0.028), and *81 (OR: 8.11; P = 0.021), were associated with an increased risk of hypersensitivity. Conversely, carriers of HLA-B *15 were associated with a reduced risk of hypersensitivity (OR: 0.43; P < 0.001). Third, HLA-C *04 was associated with an increased risk of hypersensitivity (OR: 3.09; P < 0.001), whereas a lower risk for hypersensitivity was observed in patients who were carriers of HLA-C *02 (OR: 0.22; P = 0.030), *03 (OR: 0.53; P = 0.049), and *07 (OR: 0.61; P = 0.044). Finally, carriers of HLA-DRB1 *05 (OR: 0.18; P = 0.006) and *15 (OR: 0.23; P = 0.013) were associated with a reduced risk of hypersensitivity among patients receiving antiretroviral therapy. CONCLUSIONS: The findings of this meta-analysis indicated patients carrying HLA-A *24, HLA-B *18, *35, *39, *51, *81, HLA-C *04 were associated with a higher risk of hypersensitivity. Conversely, subjects carrying HLA-B *15, HLA-C *02, *03, *07, HLA-DRB1 *05, *15 were associated with a reduced risk of hypersensitivity. FAU - Hu, Kun AU - Hu K AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Xiang, Qian AU - Xiang Q AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Wang, Zhe AU - Wang Z AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. AD - Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Peking University Health Science Center, 38# Xueyuan Road, Haidian District, Beijing, China. FAU - Mu, Guang-Yan AU - Mu GY AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Zhang, Zhuo AU - Zhang Z AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Ma, Ling-Yue AU - Ma LY AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Xie, Qiu-Fen AU - Xie QF AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Chen, Shu-Qing AU - Chen SQ AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Zhou, Shuang AU - Zhou S AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Zhang, Xiao-Dan AU - Zhang XD AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. FAU - Cui, Yi-Min AU - Cui YM AUID- ORCID: 0000-0002-4186-1005 AD - Department of Pharmacy, Peking University First Hospital, 6# Dahongluochang Street, Xicheng District, Beijing, China. cui.pharm@pkufh.com. LA - eng GR - 2016YFC0904900/National Key Technologies R&D Program/ GR - 81573504/National Natural Science Foundation of China/ GR - 81673509/National Natural Science Foundation of China/ GR - 7171012/Beijing Natural Science Foundation/ GR - 2017ZX09304028/National Science and Technology Major Projects for "Major New Drugs Innovation and Development"/ GR - 2017ZX09101001/National Science and Technology Major Projects for "Major New Drugs Innovation and Development"/ PT - Journal Article PT - Meta-Analysis DEP - 20190705 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Anti-HIV Agents) RN - 0 (Dideoxynucleosides) RN - 0 (HLA Antigens) RN - 99DK7FVK1H (Nevirapine) RN - WR2TIP26VS (abacavir) SB - IM MH - Anti-HIV Agents/*adverse effects/therapeutic use MH - Dideoxynucleosides/adverse effects/therapeutic use MH - Drug Hypersensitivity/*genetics MH - Female MH - HIV Infections/drug therapy MH - HLA Antigens/*genetics MH - Humans MH - Male MH - Nevirapine/adverse effects/therapeutic use MH - Odds Ratio MH - *Polymorphism, Single Nucleotide PMC - PMC6612203 OTO - NOTNLM OT - Antiretroviral therapy OT - HIV OT - HLA OT - Hypersensitivity OT - Polymorphisms COIS- The authors declare that they have no competing interests. EDAT- 2019/07/07 06:00 MHDA- 2019/09/24 06:00 PMCR- 2019/07/05 CRDT- 2019/07/07 06:00 PHST- 2018/05/15 00:00 [received] PHST- 2019/06/26 00:00 [accepted] PHST- 2019/07/07 06:00 [entrez] PHST- 2019/07/07 06:00 [pubmed] PHST- 2019/09/24 06:00 [medline] PHST- 2019/07/05 00:00 [pmc-release] AID - 10.1186/s12879-019-4227-5 [pii] AID - 4227 [pii] AID - 10.1186/s12879-019-4227-5 [doi] PST - epublish SO - BMC Infect Dis. 2019 Jul 5;19(1):583. doi: 10.1186/s12879-019-4227-5.