GRADE summary of findings: PrEP effectiveness
| Summary of findings table: Effectiveness 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, expressed as RRs (95% CI) | Person-years of follow-up (studies) | Certainty of the evidence (GRADE) | Comments | |
| Rate with no PrEP | Rate with PrEP | |||||
| HIV infection: MSM (all clinical trials) | 40 per 1000 | 10 per 1000 (4 to 24) | RR 0.25 (0.10 to 0.61) | 5103 (6 RCTs) | ⨁⨁⨁⨁ High†‡ | PrEP is effective in preventing HIV acquisition in MSM with a rate reduction of 75%. |
| HIV infection: MSM, trials with high (≥80%) adherence | 66 per 1000 | 9 per 1000 (4 to 23) | RR 0.14 (0.06 to 0.35) | 960 (3 RCTs) | ⨁⨁⨁⨁ High | PrEP is highly effective in preventing HIV acquisition in MSM in trials with high adherence (over 80%) with a rate reduction of 86%. |
| HIV infection: MSM, trials with low (<80%) adherence§ | 32 per 1000 | 18 per 1000 (12 to 26) | RR 0.55 (0.37 to 0.81) | 4143 (3 RCTs) | ⨁⨁⨁⨁ High | PrEP is effective in preventing HIV acquisition in MSM in trials with low adherence (under 80%) with a rate reduction of 45%. |
| HIV infection: serodiscordant couples,¶ all clinical trials: two studies with high (≥80%) adherence | 20 per 1000 | 5 per 1000 (3 to 9) | RR 0.25 (0.14 to 0.46) | 5237 (2 RCTs) | ⨁⨁⨁⨁ High | PrEP is effective in preventing HIV acquisition in serodiscordant couples with a rate reduction of 75%. |
| HIV infection: heterosexual transmission, all clinical trials | 41 per 1000 | 32 per 1000 (19 to 53) | RR 0.77 (0.46 to 1.29) | 6821 (4 RCTs) | ⨁⨁◯◯ Low†** | PrEP is not effective in preventing heterosexual HIV transmission (all trials). |
| HIV infection: heterosexual transmission, trials with high (≥80%) adherence | 31 per 1000 | 12 per 1000 (6 to 26) | RR 0.39 (0.18 to 0.83) | 1524 (1 RCT) | ⨁⨁⨁⨁ High | PrEP is effective in preventing heterosexual HIV transmission in heterosexuals in one trial with high (over 80%) adherence. This trial enrolled men and women; note that efficacy was only reported for men. |
| HIV infection: heterosexual transmission, trials with low (<80%) adherence | 45 per 1000 | 46 per 1000 (34 to 64) | RR 1.03 (0.75 to 1.43) | 5297 (3 RCTs) | ⨁⨁⨁◯ Moderate** | PrEP is not effective in preventing heterosexual HIV transmission in trials with low adherence. Note that all three trials enrolled heterosexual women. |
| HIV infection: PWID, all clinical trials: one study with low (<80%) adherence | 7 per 1000 | 3 per 1000 (2 to 6) | RR 0.51 (0.29 to 0.92) | 9666 (1 RCT) | ⨁⨁⨁◯ Moderate†† | PrEP is effective in preventing HIV transmission in PWID with a rate reduction of 49%. |
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).
†Downgraded one level for heterogeneity.
‡Upgraded one level for large effect (RR <0.5).
§Note that under alternative methods to account for zero events in one or both arms (beta-binomial), there is greater imprecision and the upper confidence bound crosses the line of no effect.
¶In studies that enrolled serodiscordant couples, the HIV-positive individual was not on antiretroviral therapy. All studies relate to serodiscordant heterosexual couples.
**Downgraded one level for imprecision.
††Downgraded one level for indirectness.
GRADE, Grading of Recommendations Assessment, Development and Evaluation; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; PWID, people who inject drugs; RCT, randomised controlled trial; RR, rate ratio.