Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: a meta-analysis

Hu, Kun; Xiang, Qian; Wang, Zhe; Mu, Guang-yan; Zhang, Zhuo; Ma, Ling-yue; Xie, Qiu-fen; Chen, Shu-qing; Zhou, Shuang; Zhang, Xiao-dan; Cui, Yi-min

doi:10.1186/s12879-019-4227-5

Table 1 Baseline characteristics of the studies included in the systematic review and meta-analysis

From: Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: a meta-analysis

Study	Study design	Publication year	Country	Ethnicity	Definition of hypersensitivity	Cases	Control	Typing method	Mean age (years)	Men/women	Intervention	NOS score
Littera [19]	Cohort	2006	Italy	Sardinian	extensive skin rash, vesicular, bullous or scaling skin lesions or skin manifestations combined with one or more of the following symptoms: fever (> 38oC),myalgia, arthralgia, visceral impairment, liver toxicity.	13	36	PCR-SSP	38.0	30/19	Nevirapine	7
Chantarangsu [20]	Case control	2009	Thailand	Thai	skin-rash (The skin reactions range from mild localized maculopapular rash, with increasing severity, to diffuse maculopapular rashes, and generalized bullous lesions. Severe fatal reactions, Stevens–Johnson syndrome, and toxic epidermal necrolysis were also observed)	147	185	SBT	35.9	157/175	Nevirapine	8
Gao [21]	Cohort	2012	China	Chinese	extensive skin rash,vesicular, bullous skin lesions, or skin manifestations combined with one or more of the following symptoms: fever (> 38 °C) or liver toxicity.	32	71	PCR-SSP	40.3	41/62	Nevirapine	8
Munderi [22]	Cohort	2011	Uganda	Kampala	fever, rash, gastrointestinal and / or constitutional symptoms and less frequently, respiratory symptoms, lethargy or malaise and usually appearing within 6 weeks of initiating abacavir (median onset 11 days)	6	241	high-resolution DNA- based assay methods	NA	NA	Abacavir	6
Mallal [23]	Cohort	2008	19 countries	mixed	fever, rash, constitutional symptoms, gastrointestinal tract symptoms, and respiratory symptoms that become more severe with continued dosing	66	781	DNA-sequence–based typing	42.0	602/245	Abacavir	8
Yuan [24]	Case control	2011	USA	mixed	Severe cutaneous toxicity [grade III or IV categorized by National Institute of Allergy and Infectious Disease Division of AIDS criteria]; symptomatic grade ≥ 3 hepatic transaminase elevation [alanine transaminase or aspartate aminotransferase > 5× upper limit of normal]; or acute hepatic failure	175	587	Illumina BeadArray technology	42.4	459/303	Nevirapine	8
Pavlos [25]	Case control	2017	USA	USA	Severe cutaneous toxicity [grade III or IV categorized by National Institute of Allergy and Infectious Disease Division of AIDS criteria]; symptomatic grade ≥ 3 hepatic transaminase elevation [alanine transaminase or aspartate aminotransferase > 5× upper limit of normal]; or acute hepatic failure	151	413	PCR amplified	> 18	NA	Nevirapine	7
Carr [26]	Cohort	2013	Malawi	Malawian	widespread rash and systemic manifestations such as fever, cough, or abnormal liver function tests	117	155	SBT	NA	NA	Nevirapine	7
Martin [27]	Cohort	2005	Australia	mixed	fever, hepatitis or rash.	14	221	Serological and SBT or PCR-SS	NA	NA	Nevirapine	7
Vitezica [28]	Cohort	2008	France	White	rash. No liver toxicity was boserved.	6	15	PCR-SSP	NA	NA	Nevirapine	6
Umapathy [29]	Case control	2011	India	Indian	fever, hepatitis, skin rash with clinical complications	40	40	serological	NA	NA	Nevirapine	7
Phillips [30]	Cohort	2013	South Africa	mixed	fever, skin rash and/or hepatitis	57	111	SBT	32.0	55/113	Nevirapine	7
Likanonsakul [31]	Case control	2009	Thailand	Thai	rash	39	60	PCR-SSP	38.4	53/46	Nevirapine	7
Keane [32]	Cohort	2014	Australia	mixed	fever, and/or rash and/or hepatitis	19	262	Serological and SBT or PCR-SS	40.3	247/34	Nevirapine	8
Gatanaga [33]	Cohort	2007	Japan	Japanese	extensive skin rash (accompanied by fever > 38 °C in three) and one patient with chronic hepatitis C who developed nevirapine-induced hepatotoxicity with aspartate aminotransferase/ alanine aminotransferase values three times above the baseline	12	29	PCR-SSP	NA	NA	Nevirapine	6
Gozalo [34]	Cohort	2011	France	mixed	either grade 3 or 4 cutaneous toxicity or alanine aminotransferase elevation greater than three times the upper limit of normal and without other causes being identified.	12	60	PCR-SSO	36.0	53/19	Nevirapine	7
Manglani [35]	Cohort	2018	India	Indian	fever, rash, nausea and vomiting	11	89	PCR-SSP	11.0	61/39	Abacavir	7

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