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. 2020 Aug 12;73(9):e3545–e3554. doi: 10.1093/cid/ciaa1169

Table 3.

Adverse Events Among Participants Included in the Safety Population

4RIF 9INH
Outcome Participants Experiencing Event Percent (95% CI) Participants Experiencing Event Percent (95% CI) Percent (95% CI) Risk Difference (4RIF-9INH)
Total safety population N = 3280 N = 3205
 Any drug-related adverse event 68 2.1 (1.6 to 2.6) 131 4.1 (3.4 to 4.8) −1.9 (−2.7 to −1.1)
 Any drug-related grade 3–5 adverse event 31 0.9 (.6 to 1.3) 75 2.3 (1.8 to 2.9) −1.3 (−1.9 to −.7)
 Drug-related grade 1–4 rash or grade 3–4 hematologic 31 0.9 (.6 to 1.3) 13 0.4 (.2 to .7) 0.5 (.1 to .9)
 Drug-related grade 3–4 hepatotoxicity 11 0.3 (.2 to .6) 65 2.0 (1.6 to 2.6) −1.6 (−2.1 to −1.1)
People living with human immunodeficiency virus N = 130 N = 138
  Any drug-related adverse event 2 1.5 (.2 to 5.4) 5 3.6 (1.2 to 8.3) −2.1 (−5.9 to 1.6)
  Any drug-related grade 3–5 adverse event 1 0.8 (.0 to 4.2) 5 3.6 (1.2 to 8.3) −2.9 (−6.3 to .6)
  Drug-related grade 1–4 rash or grade 3–4 hematologic 0 0.0 (.0 to 2.8) 0 0.0 (.0 to 2.6) 0.0 (–)
  Drug-related grade 3–4 hepatotoxicity 0 0.0 (.0 to 2.8) 5 3.6 (1.2 to 8.3) −3.6 (−6.7 to −.5)
Renal failure or use of tumor necrosis factor-alpha inhibitors N = 74 N = 58
  Any drug-related adverse event 8 10.8 (4.8 to 20.2) 5 8.6 (2.9 to 19.0) 2.1 (−7.2 to 11.3)
  Any drug-related grade 3–5 adverse event 2 2.7 (.3 to 9.4) 3 5.2 (1.1 to 14.4) −2.2 (−8.4 to 4.0)
  Drug-related grade 1–4 rash or grade 3–4 hematologic 3 4.1 (.8 to 11.4) 0 0.0 (.0 to 6.2) 4.0 (−.4 to 8.6)
  Drug-related grade 3–4 hepatotoxicity 1 1.4 (.0 to 7.3) 3 5.2 (1.1 to 14.4) −3.5 (−9.2 to 2.3)
Injection or nonprescription drug use or hepatitis N = 54 N = 51
  Any drug-related adverse event– 1 1.9 (.0 to 9.9) 2 3.9 (.5 to 13.5) −1.9 (−8.1 to 4.2)
  Any drug-related grade 3–5 adverse event 1 1.9 (.0 to 9.9) 1 2.0 (.0 to 10.4) −0.1 (−5.1 to 4.9)
  Drug-related grade 1–4 rash or grade 3–4 hematologic 0 0.0 (.0 to 6.6) 0 0.0 (.0 to 7.0) 0.0 (–)
  Drug-related grade 3–4 hepatotoxicity 0 0.0 (.0 to 6.6) 1 2.0 (.0 to 10.4) −2.0 (−5.8 to 1.8)
Diabetes mellitus N = 91 N = 82
  Any drug-related adverse event 3 3.3 (.7 to 9.3) 6 7.3 (2.7 to 15.2) −3.2 (−9.2 to 2.8)
  Any drug-related grade 3–5 adverse event 1 1.1 (.0 to 6.0) 4 4.9 (1.3 to 12.0) −3.2 (−7.8 to 1.3)
  Drug-related grade 1–4 rash or grade 3–4 hematologic 1 1.1 (.0 to 6.0) 0 0.0 (.0 to 4.4) 1.1 (−1 to 3.2)
  Drug-related grade 3–4 hepatotoxicity 0 0.0 (.0 to 4.0) 4 4.9 (1.3 to 12.0) −4.9 (−9.5 to −.2)
Alcohol use or smoking history N = 747 N = 740
  Any drug-related adverse event 9 1.2 (.6 to 2.3) 34 4.6 (3.2 to 6.4) −3.1 (−4.7 to −1.5)
  Any drug-related grade 3–5 adverse event 4 0.5 (.1 to 1.4) 22 3.0 (1.9 to 4.5) −2.2 (−3.5 to −1.0)
  Drug-related grade 1–4 rash or grade 3–4 hematologic 5 0.7 (.2 to 1.6) 2 0.3 (.0 to 1.0) 0.4 (−.3 to 1.0)
  Drug-related grade 3–4 hepatotoxicity 2 0.3 (.0 to 1.0) 21 2.8 (1.8 to 4.3) −2.4 (−3.6 to −1.2)
No concomitant health condition of interest N = 2184 N = 2136
  Any drug-related adverse event 45 2.1 (1.5 to 2.7) 79 3.7 (2.9 to 4.6) −1.5 (−2.5 to −.6)
  Any drug-related grade 3–5 adverse event 22 1.0 (.6 to 1.5) 40 1.9 (1.3 to 2.5) −0.8 (−1.5 to −.1)
  Drug-related grade 1–4 rash or grade 3–4 hematologic 22 1.0 (.6 to 1.5) 11 0.5 (.3 to .9) 0.5 (.0 to 1.0)
  Drug-related grade 3–4 hepatotoxicity 8 0.4 (.2 to .7) 31 1.5 (1.0 to 2.1) −1.0 (−1.6 to −.5)

Drug-related events are those resulting in permanent discontinuation of treatment that were judged possibly or probably related to the study drug. Exact binomial CIs for proportions calculated using the Clopper-Pearson method. Risk differences and CIs calculated using generalized estimating equations with a binomial distribution and identity link, accounting for clustering at the household level. If no events occurred in 1 subgroup, CIs were estimated using exact binomial CIs.

Abbreviations: 4RIF, 4 months daily rifampin; 9INH, 9 months daily isoniazid; CI, confidence interval.