Table 1.
Specific HLA alleles associated with increased HIV progression in two independent ART-naive cohorts
| Discovery cohort: RV152 (n = 65) | |||||
|---|---|---|---|---|---|
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| HIV outcome | HLA allele | n (%) | HR | 95% CI | p value (q valuea) |
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| Time to CD4 <350 cells/mm3 | A*02:07 | 12 (18) | 3.9 | 1.6, 9.47 | 0.003 (0.028)c |
| B*46:01 | 20(31) | 5.01 | 2.19, 11.47 | 0.0001 (0.004)c | |
| C*01:02 | 24 (37) | 3.9 | 1.82, 8.34 | 0.0005 (0.007)c | |
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| GMR | 95% CI | p value (q valuea) | |||
|
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| VL copies/mL | A*02:07 | 12(18) | 1.59 | 0.59, 4.24 | 0.36 (0.98) |
| B*46:01 | 20(31) | 2.74 | 1.32, 5.66 | 0.007 (0.20)c | |
| C*01:02 | 24 (37) | 2.24 | 1.16, 4.34 | 0.02 (0.26) | |
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| Validation cohort: BMCS (n = 207) | |||||
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| n (%) | HR | 95% CI | p value (q valueb) | ||
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| Time to CD4 < 350 cells/mm3 | A*02:07 | 35 (17) | 1.53 | 1.01, 2.33 | 0.047 (0.07)c |
| B*46:01 | 43(21) | 1.5 | 1.00, 2.25 | 0.048 (0.07)c | |
| C*01:02 | 51 (25) | 1.33 | 0.91, 1.95 | 0.14(0.14) | |
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| GMR | 95% CI | p value (q valueb) | |||
|
| |||||
| VL copies/mL | A*02:07 | 35 (17) | 2.92 | 1.36, 6.3 | 0.007 (0.02)c |
| B*46:01 | 43(21) | 2.09 | 1.02, 4.28 | 0.044 (0.07)c | |
| C*01:02 | 51 (25) | 1.68 | 0.86, 3.3 | 0.13(0.13) | |
See also Table S2.
HR, hazard ratio; GMR, geometric mean ratio; CI, confidence interval.
a
q value was adjusted for multiple comparisons (31 common HLA class I alleles) to control for false discovery rate (FDR). The covariates age, sex, baseline behavioral risk, and the calendar year of HIV-1 infection diagnosis (2003–2005, 2006, 2007, 2008, and 2009) were adjusted in all RV152 data analyses. CD4 counts were also adjusted in the RV152 VL analysis.
b
q value was adjusted for three HLA alleles to validate the RV152 findings. Age as a covariate was adjusted in the BMCS data analyses.
c
Significant HLA associations (p < 0.05, q < 0.2)