Table 3.
Safety endpoints comparing dolutegravir-based ART with standard of care*
| Dolutegravir | Standard of care | Dolutegravir versus standard of care | ||
|---|---|---|---|---|
| Participants | 42 | 43 | .. | |
| Serious adverse events† | ||||
| Number of events | 15 | 19 | .. | |
| Number of participants | 11 | 11 | HR 1·08 (0·47 to 2·49), p=0·86 | |
| Grade ≥3 adverse events† | ||||
| Number of events | 36 | 34 | .. | |
| Number of participants | 19 | 21 | HR 0·93 (0·50 to 1·74), p=0·83 | |
| ART-modifying events (any grade)† | ||||
| Number of events | 0 | 2‡ | .. | |
| Number of participants | 0 | 2 | NE | |
| Metabolic outcomes | ||||
| Mean change (SE) in total cholesterol, mg/dL, from baseline to 96 weeks†§ | 4·5 (5·6) | 29·6 (5·9) | −24·4 (−40·3 to −8·5), p=0·0032 | |
| Anthropometric measures | ||||
| Mean change (SE) in weight, kg, from baseline to 96 weeks§¶ | 5·0 (0·2) | 5·1 (0·2) | −0·1 (−0·8 to 0·5), p=0·67 | |
| Mean change (SE) in BMI-for-age z score from baseline to 96 weeks§¶ | 1·1 (0·3) | 1·5 (0·3) | −0·3 (−1·1 to 0·5), p=0·50 | |
| Mean change (SE) in weight-for-age z score from baseline to 96 weeks§¶ | 1·2 (0·2) | 1·2 (0·2) | 0·00 (−0·5 to 0·5), p=1·00 | |
ART=antiretroviral therapy. NE=not estimable.
Comparisons of treatment groups are presented for the dolutegravir group as compared with the standard of care group.
This secondary safety endpoint was specified in the protocol; additional secondary endpoints are presented in the appendix (pp 54–62); adverse events were compared between treatment groups using HRs for time to first event, adjusting for trial cohort (ODYSSEY A or ODYSSEY B).
One event was raised liver enzymes, which was considered ART-modifying as the event led to the participant stopping their first-line ART regimen for 14 weeks, after which the participant restarted the same first-line ART regimen; the other event was vomiting, which led to substitution of the third agent.
Mean changes in continuous measures from baseline to 96 weeks were calculated with the use of normal regression with adjustment for baseline measure; estimates are presented for mean change in total cholesterol from a baseline value of 127·9 mg/dL; for mean change in weight from a baseline weight of 8·1 kg; for mean change in BMI-for-age z score from a baseline z score of −0·9; and for mean change in weight-for-age z score from a baseline z score of −2·2; between-group differences in mean changes were calculated with the use of normal regression with adjustment for baseline measure and enrolment in ODYSSEY A or ODYSSEY B.
This endpoint was not a prespecified secondary endpoint in the protocol, but was included in a planned analysis in the statistical analysis plan.