Long-term survivors (LTS) of HIV, including individuals diagnosed before the availability of effective antiretroviral therapy (ART), have played a pivotal role in shaping the HIV response. Despite an increase in their number in the United States, their unique medical, social and economic challenges remain underrepresented in HIV policy and research, particularly in the context of HIV cure advancements. While an HIV cure may alleviate ART-related burdens, LTS fear unintended consequences, including the potential loss of critical social benefits, economic support and healthcare access. This study explores the policy priorities of LTS, addressing their current unmet needs and the broader implications of an HIV cure.
We conducted qualitative interviews with 32 LTS across diverse racial, gender and geographic backgrounds, recruited through community-based organizations and research networks from 2023 to 2024. Using inductive thematic analysis, we identified key policy concerns and recommendations based on participants’ lived experiences. Data collection continued until thematic saturation was reached.
LTS emphasized four pressing policy domains: (1) Persistent Healthcare Disparities: Participants reported fragmented Medicare and Medicaid coverage, limited access to essential services (e.g. dental, vision and mental healthcare), and ongoing stigma and discrimination in healthcare settings. (2) Social and Economic Precarity: Housing instability, financial insecurity and employment barriers disproportionately affect LTS, many of whom face systemic barriers to re-entering the workforce. (3) Policy Implications of an HIV Cure: Participants voiced concerns that an HIV cure, while promising, could result in disqualification from disability and social assistance programmes, exacerbating socio-economic vulnerabilities. (4) Structural Reforms for LTS Inclusion: LTS underscored the urgent need for their direct involvement in HIV research, policy development and decision-making to ensure equitable, community-driven solutions.
Policymakers must address comprehensive healthcare access, economic stability and social protections for LTS of HIV. HIV cure research must not undermine existing benefits or widen disparities. Ensuring LTS representation in decision-making is critical to developing equitable policies that safeguard their wellbeing before and after a cure.
Multiple effective antiretroviral-based pre-exposure prophylaxis (PrEP) modalities for HIV-1 prevention are now available or under investigation but their safe rollout requires implementable HIV-1 testing strategies that accurately identify rare cases of HIV-1 acquisition. Current PrEP testing guidelines and testing algorithms in PrEP studies are varied, using single or combinations of rapid antibody-based diagnostic testing, qualitative or quantitative nucleic acid testing, and/or sample collection for retrospective analyses with sensitive research assays for HIV-1 nucleic acid detection. The objective of this commentary is to summarize current and alternative HIV testing approaches for PrEP implementation to guide best practices for individual programmes.
Diagnosing HIV-1 in PrEP users is challenging because (1) rarity of breakthrough HIV-1 in individuals on PrEP that increases the risk of a false-positive test; (2) modification of acute HIV infection by PrEP; and (3) PrEP delivery in community settings with inadequate testing infrastructure. Current best practices indicate the use of rapid diagnostic tests or self-testing as recommended by national testing algorithms and the World Health Organization (WHO). The use of nucleic acid testing such as plasma HIV-1 RNA polymerase chain reaction may allow earlier detection of HIV-1 but feasibility and risk of false positive are downsides. Sensitive tests to detect single-copy HIV-1 RNA in plasma and integrated proviral DNA in blood mononuclear cells may be important methods to resolve ambiguous HIV-1 diagnosis in research settings. Delayed diagnoses could lead to drug resistance emergence under long-acting PrEP selection, whereas single unconfirmed false-positive tests could create diagnostic challenges in users of long-acting PrEP. The cost, feasibility and positive predictive value of HIV tests are important considerations for PrEP programmes.
Optimal strategies to detect HIV-1 acquisition among users of different PrEP modalities are evolving. While new guidance from the WHO recommends HIV-1 testing by serological assays or self-testing with PrEP use, feasible plans for clinical management of rare cases of breakthrough on PrEP and ambiguous diagnoses are still needed. The data from PrEP studies and scale-up will help us assess the value of different tests and testing approaches for their inclusion in HIV detection algorithms across PrEP modalities.
In the last decade, pre-exposure prophylaxis (PrEP) has revolutionized HIV prevention. The World Health Organization first recommended daily oral PrEP containing tenofovir as an additional prevention option for all populations at substantial risk of HIV in 2015 [1], then added a recommendation for event-driven or “on-demand” PrEP for men in 2019 [2], the monthly dapivirine vaginal ring for women in 2021 [3] and long-acting injectable cabotegravir (CAB-LA) in 2022 [4]. More PrEP options are becoming available, such as lenacapavir, which is administered as a sub-cutaneous injection. Recent clinical trial results suggest lenacapavir injections every 6 months are highly efficacious [5, 6], and early safety and pharmacokinetic data show potential for once-yearly dosing [7].
Despite the promise of PrEP and the recent proliferation of products, the programmatic rollout of PrEP has been challenging, as system-level constraints (e.g. cost, policy, operational barriers), social-level factors (e.g. stigma and lack of normalization of HIV prevention) and individual behaviours (e.g. adherence) have all contributed to limiting overall impact [8-10]. However, more countries have recently adopted PrEP into national guidelines, and global use of PrEP has increased substantially over the last several years [11]. Research suggests that expanding the menu of PrEP options to better meet the diverse needs and preferences of end users could improve uptake and use [12]. The advent of PrEP methods with different administration routes, discreet formulations and less frequent dosing will potentially enable easier access, more effective use, reduce stigma and, in some cases, allow for the implementation of more flexible delivery channels.
To collate early evidence related to expanding access to a choice-based HIV prevention market, we invited investigators and research teams across the globe to submit multidisciplinary articles for this supplement, designed to speak to the evaluation and delivery of PrEP choice in diverse settings and for varied populations. After careful consideration, the editorial team selected 15 contributions that illustrate current evidence, implementation learnings and challenges associated with the introduction, uptake and continued use of PrEP within the context of an expanded HIV prevention method-mix.
Choice in PrEP methods and service delivery approaches have the potential to improve prevention coverage. In a commentary by Schmidt et al. [13], the authors highlight that despite the significant strides made in accelerating oral PrEP scale-up, it is unlikely that global PrEP targets will be met. In the era of PrEP choice, the authors remind readers that choice is not only about PrEP methods, but also service delivery approaches that have the potential to transform global HIV prevention efforts and m
Eswatini prepared for the national rollout of HIV pre-exposure prophylaxis (PrEP) choice through a mixed-method demonstration study introducing the PrEP dapivirine vaginal ring in 12 Ministry of Health-supported sites. The Eswatini PrEP Ring Study aimed to describe user preferences for, and experiences with, the PrEP ring, and provider impressions. The objective was to provide real-world data on client preferences and experiences related to PrEP choice, and healthcare provider perspectives on the feasibility and acceptability of offering PrEP choice. A subset of quantitative findings is presented here.
During May 2023–August 2024, 12 study sites in Eswatini began offering a choice between the PrEP ring and oral PrEP to women 18 years and older who were HIV negative, not pregnant or breastfeeding, and interested in PrEP. Current oral PrEP users who were satisfied with the method were not recruited. Users’ early experiences with the PrEP ring were assessed through structured enrolment and follow-up questionnaires. Factors associated with choosing the PrEP ring at enrolment were assessed using logistic regression. During the first 2 months of offering PrEP choice, providers (n = 16) completed a structured questionnaire on the feasibility and acceptability of PrEP choice service delivery. Clinical Trial Number: NCT05889533
At enrolment, 69% (n = 625/904) chose the PrEP ring. Predictors for choosing the ring included ages 25+ (25–34 years AOR = 1.44, 95% CI [1.03, 2.02]; ages 35+ years AOR = 1.69, 95% CI [1.07, 2.68]), higher education (AOR = 1.71 for some/completed high school, 95% CI [1.20, 2.43]; AOR = 1.87 for vocational/tertiary education, 95% CI [1.21, 2.90]) and using either longer-acting (AOR = 2.23, 95% CI [1.28, 3.89]) or shorter-acting contraceptives (AOR = 1.63, 95% CI [1.14, 2.32]) versus no modern family planning method. Participants reported high levels of ease and confidence (98%) in using the ring. Ninety-four percent of PrEP counsellors (n = 8) and nurses (n = 8) felt prepared to offer PrEP choice and liked choice counselling but had concerns about clients’ ability to return on time for refills of either method.
Many women in Eswatini were willing to try the PrEP ring. Providers were enthusiastic about counselling on PrEP choice and introducing women to the ring.
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