The diagnosis of acute HIV infection (AHI) is challenging in routine settings because it cannot be detected by routine third-generation antibody rapid diagnostic tests (RDTs). The current fourth-generation antibody/antigen RDT, Determine™ HIV Early Detect, has demonstrated high sensitivity in laboratory studies, but field evaluations at the point of care are lacking. We nested a diagnostic accuracy study within a larger study of the burden of sexually transmitted infections in rural Eswatini.
Adults were enrolled at six routine HIV testing sites (HTS) in the Shiselweni region between June 2022 and April 2023. Determine™ HIV Early Detect was performed by HTS counsellors in parallel with routine HIV testing using a finger-prick blood sample. The reference test was HIV viral load (VL) in the plasma sample, performed on the Xpert platform in the central laboratory. AHI was defined as a negative or discordant HIV test result according to the national serial RDT algorithm and an HIV VL >10,000 copies/ml, or two consecutive HIV VL measurements between the lower limit of detection (40 copies/ml) and 10,000 copies/ml. Established HIV infection was defined as a positive serial RDT test, and overall HIV infection as either established HIV infection or AHI.
One thousand one hundred and sixty-three participants had all test results available; 49 (4.2%) were diagnosed with HIV (39 with established HIV according to the serial RDT algorithm and 10 with AHI). AHI prevalence among participants with HIV negative or discordant routine RDT results was 0.9% (10/1124). The sensitivity of Determine™ HIV Early Detect to detect overall HIV infection was 83.7% (95% CI 70.3–92.7) and to detect AHI was 20% (95% CI 2.5–55.6%); the specificity was equally high for both 99.8% (95% CI 99.4–100).
The low sensitivity of Determine™ HIV Early Detect to detect AHI when performed at the point of care using finger-prick blood samples in our study contrasts with other published evaluations from laboratory settings and highlights the importance of field evaluations of the commonly used diagnostic tests.
Post-exposure prophylaxis (PEP) is an important component of comprehensive HIV prevention, yet its uptake has been suboptimal globally. In July 2024, the World Health Organization (WHO) updated its global guidance on PEP to include two new recommendations intended to increase timely access to and delivery of PEP. These recommendations specifically aim to expand both where PEP can be delivered, to include community settings, and who can provide PEP, to include community health workers and task-sharing. The practical realities of adopting new public health guidelines to achieve the intended benefits in most contexts are complex. Articulating these realities is important for identifying what will be required to ensure the feasibility of expanded PEP access in community settings.
We provide stakeholder perspectives from five African countries—Kenya, Nigeria, South Africa, Uganda and Zimbabwe—on both barriers to and strategies for implementing the new WHO PEP recommendations. These perspectives are informed by experiences in these countries that were shared at a recent workshop and highlight key themes related to PEP uptake and use: awareness and acceptability; administration and monitoring; policy alignment, including regulatory considerations; logistics; integration of services; stakeholder involvement and capacity building; and linking PEP and PrEP more directly. Running across these themes are the roles of socio-cultural norms and the need for increased resources to pay for implementing the recommendations, including capacity strengthening and monitoring in communities.
While significant challenges exist to expanding PEP access in community settings and through task-sharing, there are examples from our countries of successful efforts to mitigate them by leveraging existing community resources and capacities in innovative ways. Additional efforts will require engagement across multiple stakeholders to address remaining awareness gaps, logistical and regulatory obstacles, and political will. As countries work to update their guidelines and align with the new WHO recommendations, continued collaboration and innovation within and across countries will be essential to realize the full potential of PEP in comprehensive HIV prevention efforts.
New longer-acting antiretroviral (ARV) drugs—that is single doses with antiviral activity for at least a month—are being utilized for HIV treatment and pre-exposure prophylaxis (PrEP) but have not been explored for post-exposure prophylaxis (PEP). A “one-and-done” simplification of PEP has the potential to serve the HIV prevention needs of individuals not being met with traditional services and expand overall biomedical HIV prevention coverage. We discuss challenges with the assessment of PEP effectiveness in human trials and potential study designs that could generate evidence needed to inform the use of new, single-administered, long-acting ARVs for PEP.
Challenges with determining the effectiveness of new long-acting PEP agents in human trials include the low likelihood of observing an HIV acquisition and the short period for outcome assessment (likely 1 month) following PEP administration. Additional challenges include recruiting individuals in the brief window in which they could benefit (<72 hours of a potential HIV exposure) and ethics of conducting informed consent during a period of high stress/vulnerability. Consequently, design approaches where the efficacy goal is to establish that the HIV incidence rate following PEP administration (of the standard or a novel agent) approaches zero should be considered. HIV RNA testing conducted within 5 days of a potential exposure could define prevention per exposure. Novel recruitment venues—such as community-based retail or online pharmacies—could be used to reach individuals after a potential exposure. Potential study designs include one- or two-arm individual-level product assignment aimed at demonstration of short-course efficacy or longer-term effectiveness compared to a background rate; cluster-randomized controlled trials of recruitment venues; and novel individual-level approaches that either do not or do utilize randomization in combination with choice, enabling assessment of preferences and effectiveness.
Over the past decade, multiple new HIV PrEP products—but no new PEP products—have been developed to meet the diverse needs of individuals seeking HIV prevention services. Challenges exist with generating PEP effectiveness evidence, but they are not insurmountable. Effectiveness research on new PEP products could advance the number of HIV prevention options available.
In Mozambique, post-exposure prophylaxis (PEP) to prevent HIV is offered as part of the essential package of post-violence care services at 1450 health facilities. However, HIV PEP access and adherence continue to be a challenge. Healthcare providers were interviewed to identify and synthesize their recommendations for improving PEP access and adherence.
We conducted semi-structured, in-depth interviews with 20 adolescent and adult healthcare providers (3 men and 17 women) who had a range of 2−15 years of experience from 20 health facilities across seven provinces during March–August 2023. Data were analysed using inductive and theoretical thematic analysis. We analysed how frequently health providers mentioned specific recommendations.
Regarding PEP access, healthcare providers recommended community education as the most effective strategy (10 mentions). In particular, providers cited the importance of palestras [community health talks]. Providers also commonly highlighted the need to have PEP kits prepared (7 mentions) and PEP readily available at health facilities (6 mentions). Regarding PEP adherence, providers recommended client counselling/education (13 mentions) to ensure clients understand the importance of taking PEP, how to properly take PEP and the potential side effects, which can often deter clients from adhering. Additionally, providers highlighted chamadas preventivas [follow-up telephone calls] within 2 weeks or so after the initial visit (9 mentions) as the best means to ensure clients complete the full, 28-day regimen and return for retesting after 3 months. Healthcare providers explained that follow-up telephone calls, despite the client living far from the health facility, can create a bond that supports clients. Providers recommended the institutionalization of follow-up telephone calls for consistent implementation in all healthcare facilities that offer PEP.
Interviewed healthcare providers offered valuable insights and recommendations to improve PEP access and adherence, which could be considered for implementation in Mozambique and other sub-Saharan African countries.
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
In Eswatini, HIV incidence among adolescent girls and young women (AGYW), aged 15–24 years, is 10 times that of their male peers. Despite the World Health Organization's 2014 recommendation for post-exposure prophylaxis (PEP) to be available for all HIV exposures, it has been underutilized among youth. PEP is an effective prevention method, and a better understanding of the characteristics, risk factors and behaviours that are associated with PEP awareness, as a precursor to effective use, is needed.
Using data from the 2022 Eswatini Violence Against Children and Youth Survey, we used logistic regression models to explore the relationships between PEP awareness and a set of hypothesized explanatory variables among AGYW aged 13–24 years who had ever had sex (N = 2648). Explanatory variables included socio-demographic characteristics, sexual risk factors and sexual health behaviours.
A slight majority (57.3%) of AGYW who had ever had sex were aware of PEP as an HIV prevention method. PEP awareness increased with age (aOR 1.1, 95% CI 1.0, 1.1) and was higher among AGYW who had a sexual partner whose age was 5 or more years older in the past 12 months (aOR 1.4, 95% CI 1.1, 1.9), those who had ever taken part in an HIV prevention programme (aOR 1.6, 95% CI 1.2, 2.3) and those who had ever heard of pre-exposure prophylaxis (aOR 8.1, 95% CI 6.4, 10.2). Participants who were ever married or partnered (aOR 0.7, 95% CI 0.5, 1.0) and those who engaged in inconsistent condom use with non-spouse/main partner or multiple partners in the past 12 months (aOR 0.8, 95% CI 0.6, 1.00) had lower odds of knowing about PEP in the adjusted model.
We identified sub-optimal PEP awareness among Swazi AGYW who had ever had sex. Our findings suggest that engagement in HIV prevention programmes increased PEP awareness and that knowing about pre-exposure prophylaxis (PrEP) was associated with PEP awareness. Future efforts could include tailored PEP awareness activities and campaigns to resonate with AGYW at elevated risk of HIV and integration of PEP education into routine sexual and reproductive service delivery and school-based HIV curriculum.
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