Table 3:

Effect modification of the association between ART use and progestin concentrations by possession of variant alleles

		Main effect PG models¹				Interaction PG models²
Gene	Variant SNP (rsID)	All women (n=59 women)				No ART (n=59 women)		Efavirenz (n=11 women)				Nevirapine (n=12 women)
Gene	Variant SNP (rsID)	# women (samples) with variant	MA (n=59)	Progestin GMR (per additional variant copy) (90% CI)	p-value⁴	# women (samples) with variant	MAF (n=59)	# women (samples) with variant	MAF (n=11)	Progestin GMR fold difference per additional variant copy (90% CI)	Interaction p-value⁴	# women (samples) with variant	MAF (n=12)	Progestin GMR fold difference per additional variant copy (90% CI)	Interaction p-value⁴
CYP2B6	15582C>T (rs4803419)	9 (53)	0.08	1.48 (1.11, 1.99)	0.03	9 (42)	0.08	2 (6)	0.14	1.47 (0.85, 2.52)	0.24	1 (5)	0.04	0.68 (0.23, 2.01)	0.56
	983T>C (rs28399499)	7 (43)	0.07	1.14 (0.81, 1.60)	0.52	7 (40)	0.07	1 (3)	0.05	0.15 (0.05, 0.43)	0.004	0 (0)	0.00	--	--
	516G>T (rs3745274)⁵	39 (226)	0.33	0.80 (0.61, 1.06)	0.06	39 (185)	0.33	8 (17)	0.36	0.65 (0.30, 1.42)	0.36	8 (24)	0.33	0.88 (0.45, 1.71)	0.75
ABCB1	4046A>G (rs3842)	24 (131)	0.25	1.19 (0.96, 1.47)	0.19	24 (112)	0.25	4 (6)	0.18	0.78 (0.37, 1.61)	0.57	6 (13)	0.29	0.86 (0.53, 1.39)	0.60
	3435C>T (rs1045642)	7 (39)	0.06	1.12 (0.74, 1.69)	0.65	7 (31)	0.06	2 (4)	0.09	0.12 (0.05, 0.29)	<0.001	2 (4)	0.08	1.12 (0.50, 2.52)	0.81
	2677G>A (rs2032582a)	0 (0)	0.00	--	--	0 (0)	0.00	0 (0)	0.00	--	--	0 (0)	0.00	--	--
	2677G>T (rs2032582t)	6 (33)	0.05	1.03 (0.66, 1.59)	0.92	6 (25)	0.05	1 (4)	0.05	2.72 (0.85, 8.75)	0.16	2 (4)	0.08	1.34 (0.58, 3.10)	0.57
CYP2A6	1836G>T (rs8192726)	8 (47)	0.08	0.98 (0.71, 1.35)	0.90	8 (40)	0.08	2 (6)	0.14	0.61 (0.36, 1.03)	0.12	1 (1)	0.04	0.62 (0.17, 2.20)	0.53
CYP3A4	-392A>G (rs2740574)	56 (323)	0.77	1.11 (0.89, 1.38)	0.45	56 (268)	0.77	10 (20)	0.77	0.59 (0.33, 1.04)	0.12	12 (35)	0.71	0.68 (0.36, 1.27)	0.30
CYP3A5	6986A>G (rs776746)	16 (88)	0.15	1.26 (0.97, 1.63)	0.14	16 (73)	0.15	3 (6)	0.14	0.36 (0.17, 0.76)	0.02	4 (9)	0.17	1.70 (0.91, 3.20)	0.16
	14690G>A (rs10264272)	26 (154)	0.28	1.00 (0.83, 1.20)	0.99	26 (119)	0.28	5 (11)	0.32	1.63 (1.05, 2.53)	0.07	7 (24)	0.33	0.63 (0.39, 1.02)	0.11
	27131insT (rs41303343)	16 (100)	0.14	0.82 (0.61, 1.10)	0.26	16 (95)	0.14	2 (5)	0.09	0.26 (0.12, 0.59)	0.007	0 (0)	0.00	--	--
NR1I2 (PXR)	44477A>G (rs1523130)	14 (78)	0.12	0.83 (0.61, 1.12)	0.30	14 (63)	0.12	5 (8)	0.23	1.79 (0.88, 3.62)	0.18	2 (7)	0.08	0.94 (0.42, 2.14)	0.91
NR1I2 (PXR)	63396C>T (rs2472677)	44 (245)	0.42	1.08 (0.86, 1.36)	0.59	44 (199)	0.42	9 (18)	0.45	0.61 (0.36, 1.03)	0.12	10 (28)	0.46	0.62 (0.17, 2.20)	0.53
NR1I3	540C>T (rs2307424)	13 (76)	0.11	1.18 (0.86, 1.62)	0.39	13 (56)	0.11	2 (5)	0.09	2.49 (1.06, 5.86)	0.08	4 (15)	0.17	1.15 (0.59, 2.24)	0.73
NR1I3	1089T>C (rs3003596)	46 (267)	0.52	0.93 (0.77, 1.13)	0.55	46 (221)	0.52	11 (16)	0.55	0.76 (0.49, 1.18)	0.30	12 (30)	0.50	0.97 (0.62, 1.51)	0.90

ART=antiretroviral therapy; MAF=minor allele frequency; GMR=geometric mean ratio; SNP=single nucleotide polymorphism; rsID=reference SNP ID

Models adjusted for ART category, days from ART initiation, implant type, BMI, log of closest viral load measure, and country

Assesses the association of the variant allele with progestin concentrations independent of ART category; model estimates indicate progestin GMR with each additional variant allele copy

Assesses effect modification of the association between ART category and progestin concentrations by variant allele; model estimates indicate fold change in progestin GMR of efavirenz/nevirapine vs. no ART groups with each additional variant copy

Includes all samples from women who did not initiate ART and pre-ART samples from women who initiated regimens with efavirenz or nevirapine; therefore, all women from the sample are represented

⁴

We used a Bonferroni adjustment of significance threshold of p=0.003, but highlight here all p-values <0.05

⁵

Allele exceeds Hardy-Weinberg equilibrium threshold of p<0.001 (p=0.0001)