Table 2. Interactions underlying HLA class I disease associations in HIV-1 infection.

Four HLA class I alleles have been associated with early viral load set point in HIV-1 infection (model 1, index only). For each HLA allele we sought to determine the underlying mechanism by performing five multivariate linear regressions (model 2–6), one for each of the distance metrics. The coefficient (Coeff) and P value for the index allele and the similarity metric are recorded below. A Coeff >0 indicates an increase in viral load i.e. a detrimental effect (D), a Coeff <0 indicates a protective effect (P). In all cases gender was included as an additional covariate in the model. A slash (/) indicates that there were an insufficient number of alleles to perform the analysis. For B53:01 there were not enough similar alleles to perform the TCR or KIR analysis. Alleles with similar LILRB1 and LILRB2 binding to B53:01 were not similarly detrimental. For the protective B57 alleles, we found a clear picture that alleles with similar aKIR binding to B*57:01, B*57:02 and B*57:03 were significantly protective (model 4, ‘aKIR.FS’ row, shaded). There was also a trend for alleles with similar TCR binding and similar LILRB2 binding to be protective (model 2 TCR.FS row and model 6 LILRB2.S row). Significance codes: p<0.001 ***; p<0.01 **; p<0.05 *; p<0.1. ; P values are two tailed.

			Index allele
Model	COV.		B*53:01	B*57:01	B*57:02	B*57:03
1. Index only	index	Coeff	+0.23 D	/	−0.63 P	−0.46 P
		P val	0.02 *	/	0.005 **	0.002 **
2. Index+TCR.FS	Index	Coeff	/	/	−0.65	−0.48
		P val	/	/	0.003 **	0.001 **
	TCR.FS	Coeff	/	−0.24 P	−0.33 P	−0.24 P
		P val	/	0.069 ·	0.082 ·	0.15
3. Index+iKIR.FS	Index	Coeff	/	/	−0.64	−0.47
		P val	/	/	0.004 **	0.002 **
	iKIR.FS	Coeff	/	−0.12 P	−0.11 P	−0.08 P
		P val	/	0.19	0.32	0.47
4. Index+aKIR.FS	Index	Coeff	/	/	−0.62	−0.45
		P val	/	/	0.005 **	0.002 **
	aKIR.FS	Coeff	/	−0.41 P	−0.43 P	−0.39 P
		P val	/	0.006 **	0.017 *	0.025 *
5. Index+LILRB1.S	Index	Coeff	+0.21	/	−0.67	−0.49
		P val	0.045 *	/	0.003 **	0.001 **
	LILRB1.S	Coeff	−0.11 P	−0.25 P	−0.59 P	−0.5 P
		P val	0.65	0.27	0.22	0.27
6. Index+LILRB2.S	Index	Coeff	+0.22	/	−0.67	−0.5
		P val	0.03 *	/	0.003 **	0.0007 ***
	LILRB2.S	Coeff	−0.06 P	−0.40 P	−0.56 P	−0.7 P
		P val	0.84	0.08 ·	0.08 ·	0.08 ·