Table 1.
Baseline characteristics and outcomes by daily sertraline dose
| Sertraline Dose Cohort | Sertraline | Sertraline | ||||
|---|---|---|---|---|---|---|
| 100mg | 200mg | 300mg | 400mg | All | P-value | |
| N per group | 17 | 60 | 50 | 45 | 172 | 172 |
| Demographics | ||||||
| Age, years | 36 (32, 41) | 37 (32, 43) | 38 (33, 42) | 33 (29, 38) | 36 (32, 42) | 0·08 |
| Male sex | 11 (65%) | 41 (68%) | 31 (62%) | 30 (67%) | 113 (66%) | 0·92 |
| Prior Cryptococcal meningitis | 1 (6%) | 16 (27%) | 3 (6%) | 2 (4%) | 22 (13%) | <0·01 |
| Receiving ART | 9 (53%) | 33 (55%) | 21 (42%) | 21 (48%) | 84 (49%) | 0·58 |
| Receiving TB Therapy | 0 (0%) | 2 (3%) | 7 (14%) | 3 (7%) | 12 (7%) | 0·14 |
| Baseline Clinical Parameters | ||||||
| Glasgow Coma Scale Score <15 | 6 (35%) | 25 (42%) | 16 (32%) | 13 (30%) | 60 (35%) | 0·58 |
| Weight, kg | 52 (49, 57) | 52 (44, 61) | 50 (47, 55) | 52 (45, 56) | 52 (47, 57) | 0·91 |
| CD4 count, cells/µL | 19 (7, 114) | 25 (9, 54) | 16 (6, 50) | 20 (9, 59) | 19 (7, 57) | 0·57 |
| CSF Opening Pressure, >250 mmH2O | 8 (53%) | 36 (69%) | 24 (53%) | 25 (61%) | 93 (61%) | 0·40 |
| CSF Quantitative Culture, log10CFU/mL* | 4·8 (4·1, 5·4) | 4·4 (3·1, 5·4) | 4·9 (4·0, 5·5) | 4·3 (3·3, 5·5) | 4·6 (3·8, 5·4) | 0·46 |
| CSF WBC ≥5 cells/µL | 9 (53%) | 15 (27%) | 19 (40%) | 12 (28%) | 55 (34%) | 0·14 |
| Outcomes | ||||||
| 14-day CSF Sterility† | 6 (43%) | 25 (61%) | 22 (51%) | 20 (50%) | 73 (53%) | 0·61 |
| Paradoxical IRIS‡ | 0 (0%) | 1 (7%) | 0 (0%) | 1 (8%) | 2 (5%) | 0·58 |
| Culture-positive Relapse§ | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | -- |
| 2 week mortality | 5 (29%) | 8 (13%) | 12 (24%) | 13 (29%) | 38 (22%) | 0·21 |
| 12 week mortality | 10 (59%) | 20 (33%) | 21 (42%) | 18 (40%) | 69 (40%) | 0·30 |
Data are median (P25, P75) or N (%). P-values comparing across the four sertraline dosing groups.
Excludes those with sterile culture at diagnosis (n=19). Four persons’ cultures were unable to be quantified.
Excludes those who started with sterile CSF culture (n=12) and/or prior history of cryptococcal meningitis (n=22). Includes all quantitative culture data collected within 14 days of enrollment among 138 sertraline participants (N=14 for 100mg/day; N=41 for 200mg/day; N=43 for 300mg/day; N=40 for 400mg/day).
IRIS incidence among persons with first episode of cryptococcal meningitis, who were ART-naïve at baseline and who survived to initiate ART, and/or those who switched to second line ART after hospitalization (N=3 for 100mg/day; N=14 for 200mg/day; N=15 for 300mg/day; N=11 for 400mg/day). Includes possible IRIS cases.
No other paradoxical IRIS cases occurred among those excluded (e.g. second episodes of cryptococcosis, those already receiving effective ART).
Two culture-positive relapse cases occurred beyond the 12 week study follow-up period, one in the 100mg dose group and another with fluconazole non-compliance.