Journal of the International AIDS Society最新文献

HIV post-exposure prophylaxis (PEP) is an important but underutilized HIV prevention tool. The scientific rationale for PEP is based on (1) the known mechanism of action of antiretrovirals in interfering with HIV replication and establishment of infection, (2) animal and pharmacokinetic/pharmacodynamic studies, and (3) studies among healthcare workers and other populations treated with zidovudine-based PEP, resulting in initial PEP guidelines [1]. Since these early studies, no comparative PEP efficacy trials have been conducted. Despite the absence of efficacy data, PEP guidelines by the US Centers for Disease Control and Prevention (CDC), World Health Organization (WHO) and other agencies have been updated based on the availability of more potent and tolerable regimens, further supportive animal studies, extrapolation from treatment studies, and non-randomized research [1, 2]. Contemporary PEP recommendations consist of a 28-day, three-drug oral regimen. However, other than zidovudine for preventing vertical transmission, no antiretroviral product has a labelled indication for PEP. It is thus implemented “off-label” based on recommendations by normative bodies.

Adherence to the recommended 28-day oral PEP regimen is often suboptimal [3, 4] and incomplete adherence may contribute to HIV seroconversion [5]. New long-acting antiretroviral drug formulation could thus improve PEP effectiveness and impact. However, demonstrating the efficacy (or effectiveness) of new products as PEP faces considerable challenges, including the low likelihood of HIV acquisition following PEP initiation and an effective standard-of-care PEP regimen (as discussed by Ortblad et al. in this supplement [6]). Given the consensus about existing PEP efficacy, placebo-controlled trials are not ethical, and active-control randomized non-inferiority trials may require unfeasibly large sample sizes. Considering these challenges, do we need a regulatory path for PEP, and if so, what would it look like?

An approved indication from a trusted regulatory authority implies rigorous science, review and benefit versus risk considerations for that indication, transparently debated in public—or with public access to the process. It builds confidence among policymakers, healthcare providers and users. An approved indication authorizes the marketing of that product for that indication, possibly resulting in improved awareness and access. A labelled indication may facilitate coverage through health insurance or public healthcare systems, further improving access. More available products with a PEP indication would increase product choice, aligning with user preferences and needs and potentially improving uptake and effective use. Finally, regulatory approvals for a PEP indication may improve global access through regulation by reliance. In this process, a regulatory authority utilizes the assessment of another trus

Despite great improvements over the last decade, HIV incidence remains unacceptably high, with 1.2 million acquisitions globally in 2023, and 450,000 in sub-Saharan Africa [1]. This is way off the global target of 370,000 new HIV acquisitions. The recorded reductions in new acquisitions are attributed to the successful scale-up of HIV treatment and several prevention interventions, including pre-exposure prophylaxis (PrEP) [2]. Implementation and uptake of HIV post-exposure prophylaxis (PEP—use of antiretroviral medication to prevent HIV acquisition after a potential exposure), however, has been limited, despite it being part of World Health Organization (WHO) guidelines since 2014. In many settings, its use has been limited to occupational and sexual violence exposures, with missed opportunities for HIV prevention. PEP is an effective intervention whose improved scale-up will be important for driving the attainment of prevention targets. Although no randomized trials were conducted, evidence of efficacy comes from animal studies [3, 4], later reinforced by systematic reviews and meta-analyses [5]. In humans, evidence of efficacy comes from case series, case-control studies [6] and systematic reviews that underscore the value of PEP [7]. It is also extrapolated from clinical trials investigating perinatal transmission of HIV [8].

Prior to 2024, WHO guidelines recommended that PEP be available from centralized services which put a strain on health systems and led to delays in accessing PEP. Other barriers included a lack of knowledge on PEP among providers, particularly community-based providers, and potential beneficiaries of PEP [9]. In light of these barriers, in 2024, WHO issued new guidelines which advocate for community-based distribution of PEP and through task sharing [9].

To facilitate delayed access, PEP guidelines allow for a window of 72 hours from exposure to the first PEP dose despite limited evidence for its efficacy after 24 hours. For those who access PEP, adherence is commonly sub-optimal with 36–65% completing the full 28-day course [10] and uptake most often after the critical 24-hour window period [11]. In the 2024 guidelines, WHO did not recommend changes to the 28-day duration or window period from exposure to uptake, but instead focussed on rapid uptake and a decentralization of services to facilitate this and greater uptake in general [9]. There is recognition that some individuals using PEP will have repeated or ongoing exposures to HIV and could, therefore, benefit from transitioning from PEP to PrEP. WHO guidelines also provide guidance for this transition [9].

For sub-Saharan Africa, data on PEP is limited but, as with the global picture, uptake and availability is generally low. There are no large-scale demonstration projects and w