Table 2.
Subgroups of Children at Antiretroviral Therapy (ART) Initiation Identified From Clustering and Impact on ART Response
| Variable | Group 1 (n = 135) | Group 2 (n = 48) | Group 3 (n = 264) | Group 4 (n = 131) | P Valuee |
|---|---|---|---|---|---|
| Factors contributing to clustering | |||||
| CD4 for age | 0.03 (0.01, 0.12)a,b,c | 0.22 (0.12, 0.33)b,c,d | 0.32 (0.22, 0.48)a,d | 0.30 (0.21, 0.45)a,d | <.0001 |
| Viral load, copies/mL | 275 100 (145 100, 748 700)c | 626 600 (144 900, 1254 900)b,c | 272 000 (72 600, 673 700)a,c | 107 200 (30 600, 285 300)a,b,d | <.0001 |
| sCD14 level, mg/L | 2.5 (2.0, 2.9)b,c | 2.6 (2.2, 3.2)b,c | 2.2 (1.6, 2.6)a,c,d | 1.8 (1.4, 2.1)a,b,d | <.0001 |
| CRP level, mg/L | 6.4 (5.2, 9.2)a,c | 35.3 (17.4, 76.3)b,c,d | 4.5 (1.8, 12.1)a,c | 1.2 (0.7, 2.8)a,b,d | <.0001 |
| IL-6 level, pg/mL | 6.4 (5.2, 9.2)a,c | 26.4 (16.7, 40.0)b,c,d | 6.7 (5.3, 9.4)a,c | 4.2 (3.7, 5.0)a,b,d | <.0001 |
| TNF-α level, pg/mL | 19.8 (17.2, 23.5)a,b | 27.8 (20.6, 33.0)c,d | 25.8 (22.1, 31.7)c,d | 19.1 (17.2, 21.9)a,b | <.0001 |
| CD8 for age | 1.2 (0.8, 1.6)a,b,c | 2.2 (1.5, 2.7)b,c,d | 2.4 (1.8, 3.6)a,c,d | 1.7 (1.3, 2.4)a,b,d | <.0001 |
| IL-7 level, pg/mL | 11.0 (6.6, 19.0)a,c | 6.4 (2.0, 16.9)b,c,d | 11.3 (6.1, 18.1)a,c | 2.9 (1.4, 7.0)a,b,d | <.0001 |
| Baseline factors not contributing to clustering | |||||
| Age, y | 7.9 (5.2, 11.0) | 4.1 (1.7, 8.1) | 3.6 (1.9, 8.1) | 8.4 (5.1, 11.5) | <.0001 |
| CD4+ T-cell percentage | 3.0 (1.0, 8.0) | 12.0 (5.5, 14.0) | 13.0 (9.0, 18.0) | 15.0 (11.0, 22.0) | <.0001 |
| Hemoglobin level, g/dL | 10.6 (9.4, 11.5) | 9.6 (9.1, 10.6) | 10.3 (9.3, 11.1) | 11.6 (10.5, 12.1) | <.0001 |
| Neutrophil count, ×109 cells/L | 1.8 (1.2, 2.6) | 2.4 (1.5, 3.6) | 2.3 (1.6, 3.1) | 1.8 (1.5, 2.5) | <.0001 |
| WHO clinical stage | .11 | ||||
| 1 or 2 | 44 (32.6) | 12 (25.0) | 68 (25.8) | 48 (36.6) | |
| 3 or 4 | 91 (67.4) | 36 (75.0) | 196 (74.2) | 83 (63.4) | |
| Current WHO clinical stage 3 or 4 illness at baselinef | 42 (31.1) | 21 (43.8) | 111 (42.0) | 19 (14.5) | <.0001 |
| Tuberculosis at baseline | 9 (6.7) | 3 (6.3) | 24 (9.1) | 4 (3.1) | .17 |
| Receiving antibiotic treatment at baseline (excluding tuberculosis treatment) | 20 (14.8) | 15 (31.3) | 33 (12.5) | 17 (13.0) | .008 |
| Outcome | |||||
| Case | 55 (40.7) | 11 (22.9) | 32 (12.1) | 15 (11.5) | <.0001 |
| Died | 21 (15.6) | 7 (14.6) | 18 (6.8) | 7 (5.3) | .03 |
| Weeks from randomization to death | 19.6 (12.4, 85.9) | 5.1 (2.3, 15.3) | 16.5 (6.7, 32.9) | 136.9 (36.3, 172.0) | |
| WHO clinical stage 4 event | 25 (18.5) | 4 (8.3) | 11 (4.2) | 3 (2.3) | <.0001 |
| Weeks from randomization to first WHO clinical stage 4 event | 53.0 (6.4, 109.1) | 104.1 (47.2, 117.6) | 43.0 (26.0, 144.1) | 156.4 (4.0, 161.9) | |
| Poor immunological response | 31 (23.0) | 0 (0.0) | 8 (3.0) | 10 (7.6) | <.0001 |
| WHO clinical stage 3 or 4 or death | 44 (32.6) | 16 (33.3) | 35 (13.3) | 15 (11.5) | <.0001 |
| Malnutrition as WHO clinical stage 3 or 4 or cause of death | 10 (7.4) | 4 (8.3) | 8 (3.0) | 2 (1.5) | .03 |
| Tuberculosis | 11 (8.1) | 7 (14.6) | 10 (3.8) | 7 (5.3) | .02 |
| Hospitalized | 70 (51.9) | 24 (50.0) | 109 (41.3) | 29 (22.1) | <.0001 |
| Viral load responseg | .20 | ||||
| Responded | 20 (36.4) | 5 (23.8) | 36 (24.8) | 29 (40.8) | |
| Had blip | 21 (38.2) | 8 (38.1) | 73 (50.3) | 24 (33.8) | |
| Had persistent low-level viral load | 4 (7.3) | 1 (4.8) | 13 (9.0) | 6 (8.5) | |
| Had rebound or no response | 10 (18.2) | 7 (33.3) | 23 (15.9) | 12 (16.9) | |
Data are median values (interquartile ranges) or no. (%) of subjects.
Abbreviations: CRP, C-reactive protein; IL-6, interleukin 6; IL-7, interleukin 7; sCD14, soluble CD14; TNF-α, tumor necrosis factor α; WHO, World Health Organization.
a P ≤ .05, by the rank sum test, compared with group 2.
b P ≤ .05, by the rank sum test, compared with group 3.
c P ≤ .05, by the rank sum test, compared with group 4.
d P ≤ .05, by the rank sum test, compared with group 1.
e Based on logistic regression analysis, accounting for immunology substudy as a stratifier for the case-control outcome; χ2 or rank sum tests were used otherwise.
f See Supplementary Table 3 for details.
g Defined only among 292 of 299 children in the immunology substudy who were alive and followed up at 24 weeks (5 died at ≤24 weeks; 2 died at 25–29 weeks without a viral load measurement after week 24). See “Methods” section for definitions. Only 2 children (one each in groups 3 and 4) were nonresponders, defined as never having a viral load of <5000 copies/mL.