Table 2.

HLA Alleles and Allele Groups Significantly Associated With Hepatitis C Virus (HCV) Viral Load and Liver Disease as Detected by Aspartate Aminotransferase to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4)

Allelea	No. of womenb	Baseline HCV viral load (n= 619),β (95% CI)c	Baseline APRI >1.5 (n= 353; 75 events)OR (95% CI)d	Baseline FIB-4 >3.25 (n= 397; 68 events),OR (95% CI)d	Incident APRI >1.5 (n= 367; 64 events),HR (95% CI)e	Incident FIB-4 >3.25 (n= 383; 87 events),HR (95% CI)e	APRI >1.5 at any visit (n= 617; 139 events),OR (95% CI)f	FIB-4 >3.25 at any visit (n= 617; 155 events),OR (95% CI)f
A. Alleles significantly associated with both HCV viral load and liver disease detected by APRI and FIB-4
DQB1*0301	94	−.4 (−.6 to −.3)g	.6 (.3–1.4)	.5 (.2–1.3)	.6 (.2–1.4)	.5 (.3–1.2)	.5 (.3–1.0)h	.5 (.2–.9)i
B. Alleles significantly associated with HCV viral load
B*5101	49	−.3 (−.6 to 0)i	1.5 (.6–3.5)	1.5 (.5–4.2)	2.1 (.9–4.8)h	.8 (.3–1.8)	1.9 (1.0–3.6)	1.1 (.6–2.2)
DQA1*0500	110	−.3 (−.5 to −.1)j	.7 (.3–1.6)	.5 (.2–1.3)	.8 (.4–1.7)	.8 (.4–1.4)	.6 (.3–1.2)	.7 (.4–1.3)
DRB1*0701	107	.3 (.1–.4)jk	1.4 (.7–2.7)	1.7 (.8–3.6)	1.3 (.7–2.4)	1.1 (.6–1.8)	1.4 (.9–2.3)	1.5 (.9–2.4)
DRB1*0804	35	−.4 (−.7 to −.1)i	.3 (.1–1.6)	.2 (0–1.6)	.7 (.2–2.4)	1.3 (.5–3.0)	.6 (.2–1.6)	.7 (.3–1.6)
Rare DRB1	129	−.2 (−.4 to 0)i	.9 (.5–1.7)	.8 (.4–1.7)	1.0 (.5–1.9)	.9 (.6–1.6)	1.1 (.7–1.8)	.9 (.5–1.4)
C. Alleles significantly associated with liver disease detected by APRI and FIB-4
A*2301	87	0 (−.3 to .3)	2.1 (1.0–4.3)i	1.3 (.6–2.9)	1.4 (.8–2.7)	1.7 (1.0–3.1)h	1.9 (1.2–3.3)i	1.6 (.9–2.7)h
A*3001	54	.1 (−.2 to .3)	1.5 (.6–3.5)	.9 (.3–2.7)	1.5 (.7–3.4)	2.2 (1.2–4.2)i	1.8 (.9–3.4)h	1.7 (.9–3.3)h
A*3002	75	0 (−.2 to .3)	.2 (0–.8)i	.5 (.2–1.5)	.8 (.3–1.8)	.8 (.4–1.5)	.4 (.2–.8)i	.6 (.3–1.1)
A*3303	49	.1 (−.2 to .4)	.5 (.1–1.6)	.5 (.1–2.1)	.3 (.1–1.2)h	.5 (.2–1.5)	.4 (.1–.9)i	.4 (.2–.9)i
A*6802	51	.1 (−.1 to .4)	4.1 (1.6–10.3)jk	2.7 (.9–8.4)h	1.4 (.6–3.6)	1.0 (.4–2.3)	1.8 (.9–3.6)h	1.3 (.7–2.5)
A*7401	55	.1 (−.1 to .4)	.6 (.2–1.9)	.9 (.3–2.5)	2.2 (1.2–4.1)i	1.3 (.7–2.5)	1.8 (1.0–3.5)h	2.0 (1.1–3.6)i
B*1402	33	0 (−.3 to .3)	.5 (.1–1.9)	.4 (.1–2.6)	.4 (.1–3.0)	.3 (0–1.8)	.4 (.1–1.3)	.2 (.1–.9)i
B*1503	53	.1 (−.2 to .3)	2.2 (.9–5.7)h	2.4 (.9–6.2)h	1.9 (.9–4.1)h	1.4 (.7–3.0)	2.0 (1.0–3.7)i	1.9 (1.0–3.6)i
B*3501	72	0 (−.2 to .2)	1.5 (.6–3.5)	2.6 (1.1–6.2)i	.9 (.4–2.0)	1.0 (.5–1.9)	1.0 (.6–1.9)	1.7 (1.0–2.9)h
B*4403	58	.2 (0–.5)i	1.7 (.7–4.2)	1.8 (.7–4.5)	.8 (.3–2.1)	1.4 (.8–2.7)	1.2 (.6–2.3)	2.1 (1.1–3.8)i
Cw*0401	189	.1 (−.1 to .2)	2.0 (1.1–3.6)i	3.1 (1.6–5.9)g	1.3 (.8–2.3)	1.2 (.7–1.9)	1.4 (.9–2.1)	1.7 (1.1–2.5)i
Cw*0802	54	−.1 (−.3 to .2)	.3 (.1–1.0)i	.3 (.1–1.2)h	.8 (.3–2.3)	.8 (.3–1.9)	.5 (.2–1.1)h	.4 (.2–1.0)i
DRB1*0301	99	−.1 (−.3 to .1)	1.2 (.6–2.4)	1.2 (.5–2.8)	1.8 (1.0–3.2)i	1.4 (.9–2.4)	1.6 (1.0–2.6)h	1.5 (.9–2.5)
A homozygous	41	−.1 (−.4 to .2)	.4 (.1–1.7)	.6 (.1–2.6)	.4 (.1–1.6)	.1 (0–.8)i	.4 (.1–1.0)h	.3 (.1–.8)i
Rare B	152	.1 (−.1 to .2)	.7 (.4–1.3)	.4 (.2–1.0)i	.6 (.3–1.2)	.8 (.5–1.4)	.8 (.5–1.2)	.8 (.5–1.2)
C1 homozygous	165	−.1 (−.2 to .1)	.2 (.1–.5)g	.4 (.2–.9)i	1.0 (.6–1.8)	.9 (.5–1.4)	.5 (.3–.9)i	.6 (.4–1.0)i
C2 homozygous	108	.2 (0–.3)h	1.9 (1.0–3.7)i	2.3 (1.1–4.7)i	1.0 (.5–2.0)	1.2 (.7–2.0)	1.5 (.9–2.4)	1.5 (.9–2.4)
Class II homozygous	121	−.1 (−.3 to .1)	1.2 (.6–2.5)	1.0 (.4–2.4)	1.8 (1.0–3.3)i	1.3 (.8–2.2)	1.3 (.8–2.1)	.9 (.6–1.5)
Rare DQA1	84	0 (−.2 to .2)	.8 (.3–1.7)	1.2 (.5–3.3)	2.4 (1.1–5.1)i	1.6 (.8–3.3)	1.4 (.8–2.4)	1.0 (.6–1.9)
Common DQB1	98	−.2 (−.4 to .0)h	.8 (.3–1.7)	1.3 (.5–3.5)	.7 (.3–1.6)	.4 (.2–1.0)i	.8 (.4–1.4)	.7 (.4–1.3)

NOTE. Bold alleles and allele groups were noted to be of special interest, as discussed in the text. CI, confidence interval; HR, hazard ratio; OR, odds ratio.

^aIn addition to individual alleles, the analyses included HLA-B and -C alleles that act as ligands for killer immunoglobulinlike receptors, namely, Bw4 and Bw4I80 groups [12] and groups C1 and C2 [42, 43]; allele zygosity [13, 44]; and allele rarity [45–47]. Allele rarity was examined by comparing alleles with moderately common genotypes (second and third quartiles of allele frequency) with those with rare genotypes (first quartile) or common genotypes (fourth quartile of allele frequency) [45, 46].

^bNumber of women homozygous or heterozygous for a given allele or allele group in the total study population. Analysis-specific allele frequencies are shown in Supplementary Table 1.

^cLinear regression models of log₁₀ normalized HCV RNA levels adjusted for race/ethnicity, age, baseline CD4⁺ T cell count, and baseline human immunodeficiency virus (HIV) RNA level (β represents the absolute difference in log₁₀ HCV viral load associated with the presence of a given allele or allele group; eg, women with the DQB1*0301 have, on average, .4 log₁₀ lower HCV viral loads than women without DQB1*0301).

^dLogistic regression models of baseline liver disease adjusted for race/ethnicity, age, baseline CD4⁺ T cell count, and baseline HIV RNA level, using women with normal values for these indexes as the comparison group, as discussed in the text.

^eCox models of incident of liver disease adjusted for race/ethnicity, age, baseline APRI or FIB-4, time-dependent CD4⁺ T cell count, and time-dependent HIV RNA level. Data set was limited to women who had baseline values considerably below the threshold for liver disease, as discussed in the text.

^fLogistic regression models of liver disease at any visit adjusted for race/ethnicity, age, baseline CD4⁺ T cell count, and baseline HIV RNA level.

^gP < .001 unadjusted for multiple comparisons.

^h.05≤ P <.10, unadjusted for multiple comparisons.

ⁱ.01≤ P <.05 unadjusted for multiple comparisons.

^j.001≤ P <.01 unadjusted for multiple comparisons.

^kSignificant interaction by immune status (HIV-negative women and HIV-positive women with CD4⁺ T cell counts >500 cells/μL vs HIV-positive women with CD4⁺ T cell counts <500 cells/μL).