Designing HIV Vaccine Efficacy Trials in the Context of Highly Effective Non-vaccine Prevention Modalities
- PDF / 2,079,016 Bytes
- 27 Pages / 439.37 x 666.142 pts Page_size
- 68 Downloads / 216 Views
Designing HIV Vaccine Efficacy Trials in the Context of Highly Effective Non‑vaccine Prevention Modalities Holly Janes1 · Yifan Zhu1 · Elizabeth R. Brown1 Received: 21 August 2019 / Revised: 23 June 2020 / Accepted: 20 August 2020 © The Author(s) 2020
Abstract The evolving HIV prevention landscape poses challenges to the statistical design of future trials of candidate HIV vaccines. Study designs must address the anticipated reduction in HIV incidence due to adding new prevention modalities to the standard prevention package provided to trial participants, and must also accommodate individual choices of participants with regard to the use of these modalities. We explore four potential trial designs that address these challenges, with a focus on accommodating the newest addition to the prevention package-antiretroviral-based oral pre-exposure prophylaxis (PrEP). The designs differ with respect to how individuals who take up oral PrEP at screening are handled. An All-Comers Design enrolls and randomizes all eligible individuals, a Decliners Design enrolls and randomizes only those who decline PrEP at screening, and Single and Multi-Stage Run-In Designs enroll all but randomize only those who decline PrEP or show inadequate adherence to PrEP after one or multiple run-in periods. We compare these designs with respect to required sample sizes, study duration, and resource requirements, using a simulation model that incorporates data on HIV risk and PrEP uptake and adherence among men who have sex with men (MSM) in the Americas. We advocate considering Run-In Designs for some future contexts, and identify their advantages and tradeoffs relative to the other designs. The design concepts apply beyond HIV vaccines to other prevention modalities being developed with the aim to achieve further reductions in HIV incidence. Keywords HIV prevention · Clinical trial design · Randomized controlled trial · Vaccine
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1256 1-020-09292-1) contains supplementary material, which is available to authorized users. * Holly Janes [email protected] Extended author information available on the last page of the article
13
Vol.:(0123456789)
Statistics in Biosciences
1 Introduction Dramatic advancements have been made in recent years in antiretroviral (ARV)based prevention of HIV infection. In particular, ARV treatment of HIV-infected individuals, or Treatment-as-Prevention (TasP), has been shown to reduce the risk of HIV transmission by a dramatic 96% [8, 9], and prophylactic ARV use among HIV-uninfected individuals, or pre-exposure prophylaxis (PrEP), has been found to have high efficacy in populations that adhere to current regimens which entail daily pill taking [5, 7, 15, 17, 24, 27, 28, 38, 40]. Most recently, cabotegravir as injectable PrEP has been found to be highly effective in a trial of men who have sex with men (MSM) [32]; a trial of this same intervention in women in Africa is ongoing. Yet, HIV remains a significant public
Data Loading...
