Table 4.
GRADE summary of findings: safety of PrEP
| Summary of findings table: Safety of PrEP | ||||||
| Patient or population: HIV prevention in participants at substantial risk. Intervention: PrEP. Comparison: no PrEP | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) |
Person-years of follow-up (studies) |
Certainty of the evidence (GRADE) |
Comments | |
| Rate with no PrEP | Rate with PrEP | |||||
| Safety outcome: any adverse event | 776 per 1000 | 784 per 1000 (768 to 799) |
RR 1.01 (0.99 to 1.03) |
17 358 (10 RCTs) |
⨁⨁⨁⨁ High |
Adverse events do not occur more commonly in patients taking PrEP compared with placebo. Adverse events were common in trials (78% of patients reporting 'any' event). |
| Safety outcome: serious adverse events | 81 per 1000 | 73 per 1000 (60 to 91) |
RR 0.91 (0.74 to 1.13) |
17 778 (12 RCTs) |
⨁⨁⨁⨁ High |
Serious adverse events do not occur more commonly in patients taking PrEP compared with placebo. Serious adverse events occurred in 7% of patients in trials but most were not drug related. |
| Safety outcome: deaths | 13 per 1000 | 10 per 1000 (8 to 15) |
RR 0.83 (0.60 to 1.15) |
12 720 (11 RCTs) |
⨁⨁⨁◯ Moderate† |
Deaths did not occur more commonly in people taking PrEP compared with placebo in trials. No deaths were related to PrEP. |
| Safety outcome: drug resistance mutations in patients with acute HIV at enrolment | 53 per 1000 | 186 per 1000 (62 to 556) |
RR 3.53 (1.18 to 10.56) |
44 (5 RCTs) |
⨁⨁⨁◯ Moderate† |
Patients randomised to receive PrEP who had acute HIV at enrolment were at increased risk of developing resistance mutations to the study drug. Most conferred resistance to emtricitabine. |
Note that only a minority of studies tested for viral drug resistance mutations.
GRADE Working Group grades of evidence.
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
*The rate in the intervention group (and its 95% CI) is based on the assumed rate in the comparison group and the relative effect of the intervention (and its 95% CI).
†Imprecision was detected due to few observations.
GRADE, Grading of Recommendations Assessment, Development and Evaluation; PrEP, pre-exposure prophylaxis; RCT, randomised controlled trial; RR, rate ratio.