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Review
. 2020 Nov;7(11):e791-e796.
doi: 10.1016/S2352-3018(20)30192-2.

A Bayesian averted infection framework for PrEP trials with low numbers of HIV infections: application to the results of the DISCOVER trial

David V Glidden  1 , Oliver T Stirrup  2 , David T Dunn  3
Affiliations
Review

A Bayesian averted infection framework for PrEP trials with low numbers of HIV infections: application to the results of the DISCOVER trial

David V Glidden et al. Lancet HIV. 2020 Nov.

Abstract

Trials of candidate agents for HIV pre-exposure prophylaxis (PrEP) might randomly assign participants to be given a new PrEP agent or oral coformulated tenofovir disoproxil fumarate plus emtricitabine. This design presents unique challenges in interpretation. First, with two active arms, HIV incidence might be low. Second, the effectiveness of tenofovir disoproxil fumarate plus emtricitabine varies across populations; thus, similar HIV incidence between groups could be consistent with a wide range of effectiveness for the new PrEP. We propose a two-part approach to trial results. First, we use Bayesian methods to incorporate assumptions about the background incidence of HIV in the trial in the absence of PrEP, possibly augmented by external data. On the basis of the estimated background incidence, we estimate and compare the number of averted (or prevented) HIV infections in each of the two trial groups, calculating the averted infections ratio. We apply these methods to a completed trial of tenofovir alafenamide plus emtricitabine for PrEP. Our framework shows that leveraging external information to estimate averted infections and the averted infections ratio enhances the efficiency and interpretation of active-controlled PrEP trials.

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Conflict of interest statement

Declaration of interests

DTD reports personal fees from ViiV Healthcare and Gilead Sciences, outside of the submitted work. DVG has accepted fees from Gilead Sciences and Merck.

Figures

Fig 1:
Fig 1:
Averted versus observed infections assuming background incidence of 1.44 per 100 person years in the DISCOVER trial.
Fig 2:
Fig 2:
Averted infections ratio calculated with lower 95% confidence limit calculated from the on-study infections in the DISCOVER data by assumed background HIV incidence rate.
Fig 3:
Fig 3:
Estimated posterior density for the background HIV incidence in DISCOVER. The shaded area shows the 95% credibility interval, and the vertical line is the posterior mean.
Fig 4:
Fig 4:
Estimated posterior density for the averted infection ratio in DISCOVER. The shaded area shows the 95% credibility interval, and the vertical line is the posterior mean.
See this image and copyright information in PMC

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References

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