Table 2.
Adjusted Incidence of Cancer, by Increasing Cumulative Exposure to INSTIs, Calculated From a Range of Sensitivity Analyses
| Analysis | No. Individuals Included | No. Cancers Included | 0 Months | <6 Months | 6–<12 Months | >12–24 Months | >24–36 Months | 36+ Months | Global P Value | |
|---|---|---|---|---|---|---|---|---|---|---|
| Primary analysis | 29 340 | 1078 | Adjusted IRR (95% CI) | 1 | 1.15 (0.89–1.49) | 0.97 (0.71–1.32) | 0.84 (0.64–1.11) | 1.10 (0.82–1.47) | 0.90 (0.65–1.26) | .60 |
| No. cancers (PYFU) | 830 (127 132) | 63 (7370) | 42 (5835) | 57 (9000) | 49 (5965) | 37 (5355) | ||||
| All NADC | 29 340 | 835 | Adjusted IRR (95% CI) | 1 | 1.22 (0.90–1.65) | 1.25 (0.89–1.74) | 1.11 (0.84–1.48) | 1.31 (0.95–1.80) | 1.16 (0.82–1.65) | .32 |
| No. cancers (PYFU) | 625 (127 132) | 46 (7370) | 37 (5835) | 52 (9000) | 41 (5965) | 34 (5355) | ||||
| All ADC | 29 340 | 243 | Adjusted IRR (95% CI) | 1 | 0.86 (0.52–1.43) | 0.31 (0.13–0.77) | 0.22 (0.09–0.53) | 0.56 (0.28–1.15) | 0.25 (0.08–0.78) | .0002 |
| No. cancers (PYFU) | 205 (127 132) | 17 (7370) | 5 (5835) | 5 (9000) | 8 (5965) | 3 (5355) | ||||
| All validated cancers | 25 118 | 502 | Adjusted IRR (95% CI) | 1 | 1.25 (0.88–1.78) | 0.98 (0.65–1.47) | 0.65 (0.45–0.93) | 0.80 (0.56–1.14) | 0.77 (0.54–1.10) | .06 |
| No. cancers (PYFU) | 336 (43 381) | 36 (3300) | 26 (3061) | 34 (5795) | 34 (4656) | 36 (4880) | ||||
| Excluding individuals with cancer before baseline | 27 958 | 983 | Adjusted IRR (95% CI) | 1 | 1.12 (0.85–1.47) | 0.94 (0.68–1.31) | 0.81 (0.61–1.08) | 1.08 (0.80–1.46) | 0.87 (0.61–1.23) | .56 |
| No. cancers (PYFU) | 759 (119 581) | 57 (6910) | 38 (5499) | 51 (8470) | 45 (5614) | 33 (5023) | ||||
| Only including individuals who started a new ART | 20 782 | 574 | Adjusted IRR (95% CI) | 1 | 0.92 (0.71–1.22) | 0.84 (0.62–1.51) | 0.75 (0.57–0.99) | 0.75 (0.64–1.18) | 0.77 (0.55–1.08) | .28 |
| No. cancers (PYFU) | 312 (40 821) | 64 (7801) | 46 (6171) | 64 (9535) | 49 (6325) | 39 (5647) | ||||
| Only including individuals who started a new ART to which they were naive | 9983 | 274 | Adjusted IRR (95% CI) | 1 | 0.83 (0.56–1.24) | 0.71 (0.45–1.14) | 0.57 (0.37–0.88) | 0.74 (0.46–1.19) | 0.62 (0.36–1.07) | .08 |
| No. cancers (PYFU) | 171 (21 005) | 28 (3559) | 19 (2854) | 23 (4311) | 19 (2767) | 14 (2414) | ||||
| Using complete case analysis to account for missing data | 7071 | 298 | Adjusted IRR (95% CI) | 1 | 1.02 (0.58–1.78) | 1.72 (1.05–2.84) | 1.19 (0.74–1.91) | 1.50 (0.91–2.47) | 1.25 (0.72–2.15) | .21 |
| No. cancers (PYFU) | 218 (33 507) | 13 (1933) | 17 (1571) | 19 (2536) | 17 (1794) | 14 (1756) | ||||
| Adjusting the primary analysis for cumulative time spent with CD4 count <200 cells/mm3 | 29 340 | 1078 | Adjusted IRR (95% CI) | 1 | 1.15 (0.88–1.49) | 0.96 (0.70–1.32) | 0.84 (0.64–1.10) | 1.08 (0.81–1.45) | 0.89 (0.64–1.25) | .58 |
| No. cancers (PYFU) | 830 (127 132) | 63 (7370) | 42 (5835) | 57 (9000) | 49 (5965) | 37 (5355) |
Abbreviations: ADC, acquired immune deficiency syndrome (AIDS)-defining cancers; ART, antiretroviral treatment; CI, confidence interval; INSTI, integrase strand transfer inhibitor; IRR, incidence rate ratio; NADC, non-AIDS-defining cancers; PYFU, person years of follow-up.
NOTE: Incidence rate ratio adjusted for age, sex, ethnicity, human immunodeficiency virus risk group, ART experience, CD4 cell count, CD4 nadir, body mass index, geographical region, hepatitis B, prior diabetes, prior AIDS, prior cancer, prior chronic kidney disease, prior cardiovascular disease, prior end-stage liver disease (all fixed at baseline), and smoking status (time updated).