Table 2.
Adverse events
| Adverse event | TDF n=1584 |
FTC/TDF n=1579 |
Placebo n=1584 |
|||||
|---|---|---|---|---|---|---|---|---|
| # participants | % | P value versus placebo | # participants | % | P value versus placebo | # participants | % | |
| Any adverse event | 1350 | 85.2 | 1.00 | 1362 | 86.3 | 0.42 | 1350 | 85.2 |
| Any serious adverse event | 118 | 7.4 | 1.00 | 115 | 7.3 | 0.89 | 118 | 7.4 |
| Death* | 8 | 0.5 | 0.80 | 8 | 0.5 | 0.80 | 9 | 0.6 |
| Any grade 4 event | 34 | 2.1 | 0.64 | 44 | 2.8 | 0.58 | 39 | 2.5 |
| Any grade 3 event | 289 | 18.2 | 0.35 | 293 | 18.6 | 0.24 | 268 | 16.9 |
| Confirmed laboratory events† | ||||||||
| Elevated creatinine‡ | ||||||||
| Grade 1 | 16 | 1.0 | 0.57 | 18 | 1.1 | 0.28 | 12 | 0.8 |
| Grade 2+ | 3 | 0.2 | 0.62 | 2 | 0.1 | 0.62 | 1 | 0.1 |
| Decreased phosphorus** | ||||||||
| Grade 2 | 134 | 8.5 | 0.56 | 128 | 8.1 | 0.79 | 124 | 7.8 |
| Grade 3 | 8 | 0.5 | 0.50 | 12 | 0.8 | 1.00 | 12 | 0.8 |
Deaths were due to the following causes: TDF: trauma (2), alcohol poisoning (2), esophageal carcinoma, lung abscess, Shigella gastroenteritis, acute abdomen; FTC/TDF: trauma (3), poisoning, pulmonary embolism, pulmonary tuberculosis, gastroenteritis, acute febrile illness; Placebo: trauma (3), electrocution, suicide, hematemesis, complications of diabetes, febrile illness, hypotension.
Laboratory adverse events were confirmed by repeat testing, ideally conducted within 7 days. Only events that were confirmed on repeat testing are reported.
One confirmed grade 3 creatinine event was observed in the study, in a 46 year-old male participant in the TDF arm who had seroconverted to HIV-1 and had discontinued study medication 22 days previously. Creatinine resolved to normal after hydration. No confirmed grade 4 creatinine events were observed.
The study protocol defined that there was no grade 1 range for decreased phosphorus; no confirmed grade 4 phosphorus events were observed. Significant proteinuria (≥2+) was observed in association with 27 confirmed grade 2 phosphorus events (9 TDF, 9 FTC/TDF, 9 placebo) and 1 confirmed grade 3 event (placebo). Glycosuria ≥1+ was observed in association with 3 grade 2 confirmed phosphorus events (1 FTC/TDF, 2 placebo).
A listing of all clinical adverse events of grade 2 or higher and confirmed laboratory adverse events that were reported in >1% (n=47 or greater) of study subjects is presented in Table S9.
P-values were calculated using the Fisher’s exact test except for those comparing deaths, which are from Cox proportional hazards model of time to death.