Taking stock of the present and looking ahead: envisioning challenges in the design of future HIV prevention efficacy trials

Janes, Holly; Donnell, Deborah; Gilbert, Peter B.; Brown, Elizabeth R.; Nason, Martha

doi:10.1016/s2352-3018(19)30133-x

Cited by 23 publications

(19 citation statements)

References 39 publications

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“…On the other hand, in HVTN 702, where PrEP was provided as part of HIV standard of prevention during the trial, PrEP use (monitored by self-report and laboratory testing) was low, with only 0.9% of participants reporting PrEP use, and detectable TFV-DP found in only 2.2% of samples [ 20 ]. In a “real-world” implementation program in family planning clinics in Kenya, the uptake of PrEP was 22% [ 21 ]. Almost 90% of women felt at risk of acquiring HIV and half of these felt their partner had other sexual partners in our study.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial

et al. 2020

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HIV endpoint-driven clinical trials in Africa enroll women who are at heightened risk of acquiring HIV. In 2017, the South African Medical Research Council recommended the provision of oral pre-exposure prophylaxis (PrEP) in HIV prevention trials, at which time the Evidence for Contraceptive Options and HIV Outcomes trial was ongoing and began to provide PrEP on-site at some trial sites. We interviewed 132 women who initiated PrEP on-site at the Durban, South Africa trial site to explore PrEP use, and conducted phone-based interviews 4–6 months post-trial exit to explore post-trial PrEP access. PrEP uptake was high (42.6%). Among women initiating PrEP on-site, 87.9% felt at risk of acquiring HIV. Most women (> 90%) heard of PrEP for the first time from study staff and three-quarters who initiated PrEP on-site continued at trial-exit. PrEP use declined post-trial exit with more than 50% of women discontinuing PrEP, and barriers relating to access emerged.

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Section: Discussionmentioning

confidence: 99%

Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial

et al. 2020

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“…In other trials with HIV as the primary endpoint, HIV prevention packages provided to participants have included risk‐reduction counselling, free condoms, referral for or provision of male medical circumcision, testing and treatment of STIs, and counselling and referral for post‐exposure prophylaxis. In recent years, substantial discussion has focused on the ethical, logistical and scientific considerations regarding incorporation of oral PrEP into clinical trials with HIV as the primary endpoint, as part of a standard prevention package or an active comparator for new PrEP agents [4,10]. The ECHO Trial represents one of the first trials with incident HIV as a primary study outcome to successfully incorporate PrEP into a standard HIV prevention package, provided on site, and could be used as a model for future trials as PrEP becomes part of standard prevention services.…”

Section: Discussionmentioning

confidence: 99%

“…It is still possible to obtain study outcomes but it might take a longer period of time to achieve these; and the provision of PrEP should be factored into study power calculations. Novel trial designs and analyses are being considered in response to effective HIV prevention provision to all participants [10]. Not all women who are offered PrEP will initiate it, and not all women who initiate PrEP will continue using it or remain adherent to achieve optimal levels of protection.…”

Section: Discussionmentioning

confidence: 99%

“…Incorporating PrEP into standard of care HIV prevention services for trials with HIV outcomes has emerged as an important component of trial design and operational plans [9]. How to incorporate new prevention interventions into the standard prevention package of clinical trials comes with ethical, operational and scientific complexities, and this area is currently an active topic of ethical, advocacy and research discussion [4,10].…”

Section: Introductionmentioning

confidence: 99%

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Integrating oral PrEP delivery among African women in a large HIV endpoint‐driven clinical trial

et al. 2020

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Introduction Global guidelines emphasize the ethical obligation of investigators to help participants in HIV‐endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral pre‐exposure prophylaxis (PrEP) has increasingly become part of state‐of‐the‐art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Methods ECHO was an open‐label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part‐way through the course of the trial, oral PrEP was provided to study participants either off‐site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi‐squared tests or t‐tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression. Results PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow‐up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p < 0.05). PrEP initiation did not differ across study randomized groups (p = 0.7). Two‐thirds of PrEP users were continuing PrEP at study exit. Conclusions There is a need for improved HIV prevention services in clinical trials with HIV endpoints, especially trials among African women. PrEP as a component of a comprehensive HIV prevention package provided to women in a large clinical trial is practical and feasible. Provision of PrEP within clinical trials with HIV outcomes should be standard of prevention.

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“…Late-phase trials of experimental HIV pre-exposure prophylaxis (PrEP) agents are currently designed as active-control trials, with oral TDF-FTC, currently the only drug licensed for this indication, constituting the control regimen. In the absence of a validated surrogate, the primary endpoint is an incident HIV infection (Cutrell et al 2017; Janes et al 2019). The standard primary outcome measure, following the approach used in earlier placebo controlled trials, is the HIV incidence rate ratio comparing the experimental and control groups (Cutrell et al 2017; Donnell et al 2013).…”

Section: Introductionmentioning

confidence: 99%

The Connection between the Averted Infections Ratio and the Rate Ratio in Active-control Trials of Pre-exposure Prophylaxis Agents

Dunn

Glidden

2019

Statistical Communications in Infectious Diseases

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The design and analysis of active-control trials to evaluate experimental HIV pre-exposure prophylaxis (PrEP) agents pose serious statistical challenges. We recently proposed a new outcome measure, the averted infections ratio (AIR) – the proportion of infections that would be averted by using the experimental agent rather than the control agent (compared to no intervention). The main aim of the current paper is to examine the mathematical connection between AIR and the HIV incidence rate ratio, the standard outcome measure. We also consider the sample size implications of the choice of primary outcome measure and explore the connection between effectiveness and efficacy under a simplified model of adherence.

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Taking stock of the present and looking ahead: envisioning challenges in the design of future HIV prevention efficacy trials

Cited by 23 publications

References 39 publications

Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial

Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial

Integrating oral PrEP delivery among African women in a large HIV endpoint‐driven clinical trial

The Connection between the Averted Infections Ratio and the Rate Ratio in Active-control Trials of Pre-exposure Prophylaxis Agents

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