Table 1.
Baseline demographics and clinical characteristics of study participants by HIV and TB status
| HIV-infecteda | HIV-uninfected | |||||
|---|---|---|---|---|---|---|
| Total (N = 284) | TBb (N = 66) | Unlikely TBc (N = 218) | Total (N = 235) | TBb (N = 51) | Unlikely TBc (N = 184) | |
| Age—days | ||||||
| Median | 95 | 96 | 95 | 93# | 93 | 93# |
| Range | 91 to 120 | 91 to 120 | 91 to 120 | 91 to 120 | 91 to 119 | 91 to 120 |
| WHO weight-for-age z score | ||||||
| Median | − 1.35 | − 1.39 | − 1.10 | − 0.33# | − 0.46# | − 0.30# |
| Range | − 5.84 to 3.48 | − 5.84 to 2.17 | − 5.84 to 3.48 | − 4.96 to 1.98 | − 4.96 to 1.87 | − 3.34 to 1.98 |
| Male sex—no. (%) | 116 (40.8) | 29 (42.4) | 87 (39.9) | 126 (53.6)# | 27 (52.9)# | 99 (53.8)# |
| Race or ethnic group—no. (%) | ||||||
| Indigenous African | 283 (99.6) | 66 (100.0) | 217 (99.5) | 234 (99.6) | 51 (100.0) | 183 (99.5) |
| Mixed ancestry or other | 1 (0.4) | 0 (0.0) | 1 (0.5) | 1 (0.4) | 0 (0.0) | 1 (0.5) |
| Breast-feeding—no. (%) | ||||||
| Ever breast-fed | 42 (14.8) | 6 (9.1) | 36 (16.5) | 19 (8.1)# | 2 (4.0) | 17 (9.2)# |
| Breast-fed at baseline | 22 (7.7) | 4 (6.1) | 18 (8.3) | 3 (1.3)# | 0 (0.0) | 3 (1.6)# |
| Parent study arm—no. (%)d | ||||||
| Isoniazid | 150 (52.8) | 33 (50.0) | 117 (53.7) | 113 (48.1) | 23 (45.1) | 90 (48.9) |
| Placebo | 134 (47.2) | 33 (50.0) | 101 (46.3) | 122 (51.9) | 28 (54.9) | 94 (51.1) |
| Maternal history of tuberculosis—no. (%) | 13 (4.6) | 5 (7.6) | 8 (3.7) | 15 (6.8) | 3 (5.9) | 12 (6.5) |
| During index pregnancy | 1 (0.4) | 1 (1.5) | 0 | 1(0.4) | 0 | 1 (0.5) |
| Before index pregnancy | 12 (4.2) | 4 (6.1) | 8 (3.7) | 14 (6.4) | 3 (5.9) | 11 (6.0) |
| CDC clinical HIV category—no. (%)e | ||||||
| N (asymptomatic) | 223 (79.6) | 53 (81.5) | 170 (79.1) | – | – | – |
| A (mildly symptomatic) | 43 (15.4) | 9 (13.9) | 34 (15.8) | – | – | – |
| B (B moderately symptomatic) | 14 (5.0) | 3 (4.6) | 11 (5.1) | – | – | – |
| CD4+ percentage—% | ||||||
| Median | 30 | 25 | 30ǂ | – | – | – |
| Range | 6 to 58 | 9 to 48 | 6 to 58 | – | – | – |
| CD4+ percentage category—no. (%)f | ||||||
| < 20% | 52 (19.7) | 14 (23.7) | 38 (17.7) | – | – | – |
| 20–24% | 33 (12.5) | 14 (23.7) | 29 (13.5) | – | – | – |
| 25–34% | 104 (39.4) | 21 (35.6) | 83 (38.6) | – | – | – |
| ≥ 35% | 75 (28.4) | 10 (16.9) | 65 (30.2) | – | – | – |
| Plasma HIV-1 RNA at entry—copies/ml | ||||||
| Median | 527,000 | 750,000 | 386,000ǂ | – | – | – |
| Range | ≤ 400 to > 750,000 | ≤ 400 to > 750,000 | ≤ 400 to > 750,000 | – | – | – |
| TB related parameters—n/N (%)g | ||||||
| MTB culture | 5/111 (4.5) | 5/61 (8.2) | 0/50 (0.0) | 5/68 (7.4) i | 5/42 (11.9) | 0/26 (0.0) |
| AFB smear | 14/114 (12.3) | 9/64 (14.1) | 5/50 (10.0) | 9/70 (12.9) | 6/44 (13.6) | 3/26 (11.5) |
| TST | 78/202 (38.6) | 46/66 (69.7) | 32/136 (23.5)ǂ | 51/226 (22.6)# | 30/51 (58.8) | 21/175 (12.0)#ǂ |
| TB contact exposure | 39/41 (95.1) | 27/28 (96.4) | 12/13 (92.3) | 34/38 (89.5) | 21/24 (87.5) | 13/14 (92.9) |
| Chest X-ray | 75/134 (56.0) | 58/66 (87.9) | 17/68 (25.0)ǂ | 61/98 (62.2) | 49/51 (96.1) | 12/47 (25.5)ǂ |
| Signs/symptoms consistent with TB | 13/284 (4.6) | 10/66 (15.2) | 3/218 (1.4)ǂ | 11/235 (4.7) | 6/51 (11.8) | 5/184 (2.7)ǂ |
| Positive response to anti-TB therapyh | 38/77 (49.4) | 37/60 (61.7) | 1/17 (5.9)ǂ | 33/61 (54.1) | 32/46 (69.6) | 1/15 (6.7)ǂ |
HIV status was determined following enrollment; TB status was retroactively applied to the study population using the 2015 NIH criteria
Symbols denote p values < 0.05 for differences between the TB and unlikely TB groups (ǂ) and the HIV-infected and HIV-uninfected groups (#)
aTwo participants were HIV-uninfected at entry but tested HIV-infected approximately 24 weeks after enrollment and therefore classified as HIV-infected
bParticipants with confirmed TB (Mtb culture-positive) and unconfirmed TB (≥ 2 types of non-bacteriological evidence of TB) evaluated as a group since the size of the confirmed TB group (N = 8; see Fig. 1) prevent meaningful comparisons with other groups
cUnlikely TB: children never suspected of TB or suspected of TB but with no, or insufficient, evidence for TB diagnosis, or with a confirmed alternative diagnosis
dChildren enrolled in the P1041 parent study received INH prophylaxis for up to 96 weeks or until achieving a primary endpoint (first occurrence of TB disease or Mtb infection, or death from any cause) to evaluate whether primary INH prophylaxis improved TB disease-free survival among HIV-infected children or Mtb infection-free survival among HIV-uninfected children in a population immunized with the BCG vaccine
eFour participants with missing data and HIV-uninfected participants at entry were not included from the percentages
f20 participants with missing data and HIV-uninfected participants at entry were not included from the percentages
gn/N (%) indicate the number of children with positive results per the total number of children with this information and the percent of children with a positive result
hChildren classified as TB cases (definite, probable, and possible TB) according to the P1041 protocol or as having “non-algorithm TB” by clinical experts were started on anti-TB treatment. The majority of children identified as TB cases in the P1041 study were also categorized as TB cases by the 2015 NIH criteria (Table S10)
iTwo TB patients with culture positive results were first diagnosed as unconfirmed TB