Table 2.
Cumulative summary of safety
| Parameter, n (%) | Randomized cohort (N = 272) | Non-randomized cohort (N = 99) | Total (N = 371) | |||
|---|---|---|---|---|---|---|
| Week 96 | Week 240 | Week 96 | Week 240 | Week 96 | Week 240 | |
| Any AE | 249 (92) | 259 (95) | 98 (99) | 98 (99) | 347 (94) | 357 (96) |
| Any grade 2–4 AE | 216 (79) | 242 (89) | 87 (88) | 94 (95) | 303 (82) | 336 (91) |
| Drug-related grade 2–4 AEs | 57 (21) | 65 (24) | 22 (22) | 23 (23) | 79 (21) | 88 (24) |
| Drug-related grade 2–4 AEs occurring in ≥ 2% of participants in either cohort | ||||||
| Nausea | 9 (3) | 12 (4) | 5 (5) | 5 (5) | 14 (4) | 17 (5) |
| Diarrhea | 6 (2) | 5 (2) | 3 (3) | 3 (3) | 9 (2) | 8 (2) |
| Headache | 6 (2) | 6 (2) | 1 (1) | 1 (1) | 7 (2) | 7 (2) |
| IRIS | 6 (2) | 6 (2) | 1 (1) | 1 (1) | 7 (2) | 7 (2) |
| Vomiting | 4 (1) | 4 (1) | 2 (2) | 2 (2) | 6 (2) | 6 (2) |
| Fatigue | 3 (1) | 3 (1) | 2 (2) | 2 (2) | 5 (1) | 5 (1) |
| Asthenia | 2 (< 1) | 2 (< 1) | 2 (2) | 2 (2) | 4 (1) | 4 (1) |
| Any grade 3–4 AE | 78 (29) | 110 (40) | 49 (49) | 60 (61) | 127 (34) | 170 (46) |
| Any SAEa | 92 (34) | 122 (45) | 48 (48) | 55 (56) | 140 (38) | 177 (48) |
| Drug-related SAEsb | 9 (3) | 10 (4) | 3 (3) | 3 (3) | 12 (3) | 13 (4) |
| AEs leading to D/Cc | 14 (5) | 17 (6) | 12 (12) | 13 (13) | 26 (7) | 30 (8) |
| CDC class C events | 23 (8) | 25 (9) | 15 (15) | 19 (19) | 38 (10) | 44 (12) |
| Deathsd | 12 (4) | 15 (6) | 17 (17) | 20 (20) | 29 (8) | 35 (9) |
AE adverse event, CDC Centers for Disease Control and Prevention, D/C discontinuation, IRIS immune reconstitution inflammatory syndrome, SAE serious AE
aSAEs occurring in ≥ 2% of participants were pneumonia (n = 25), cellulitis (n = 10), acute myocardial infarction (n = 8), acute kidney injury (n = 8, all with identified reversible causes not related to study drug), COVID-19 (n = 7), sepsis (n = 6), and coronary artery disease (n = 6)
bDrug-related SAEs (16 events in 13 participants) included IRIS (n = 3); nephrolithiasis (n = 2); and 1 each of acute kidney injury, hyperglycemia, hyperkalemia, loss of consciousness, myocarditis, hepatocellular cytolysis, rhabdomyolysis, fetal growth restriction, disorientation, and rash through the Week 96 data cutoff and supraventricular tachycardia (n = 1) after the Week 96 data cutoff
cThe most common AEs leading to discontinuation were related to infections (n = 12); four participants discontinued because of an AE after the Week 96 cutoff (one each for pneumonia, cytomegaloviral pneumonia, polyneuropathy, and rash)
dOf the 35 deaths, 6 occurred since Week 96; 12 deaths were AIDS-related (5 since Week 96), 12 were acute infections (1 since Week 96), 6 were non-AIDS-related malignancies, and the remaining 5 were related to other conditions. Six deaths occurred after the participant withdrew from the study. One death occurred on the day of study withdrawal for AEs