Current opinion in HIV and AIDS最新文献

Purpose of review: Tests for HIV may perform differently in some circumstances such as with preexposure prophylaxis (PrEP) or other HIV prevention agents. Testing algorithms may not account for this, with a risk of false negative or positive HIV results. In this review we have explored the challenges of HIV testing in these special circumstances.

Recent findings: Long-acting injectable PrEP using cabotegravir or lenacapavir has been studied in large randomized controlled trials (HPTN083/084 and PURPOSE1/2 respectively). Injectable PrEP was significantly more efficacious than oral PrEP, but infections still occurred risking the emergence of HIV drug-resistance. HIV diagnostic test results were atypical in those receiving injectable PrEP, with low or undetectable HIV viral loads, delayed or diminished antibody, and HIV detection assays reverting from reactive to unreactive; so-called long acting early viral inhibition (LEVI) syndrome. In these cases, missed or delayed HIV diagnoses could be reduced with the use of HIV nucleic acid amplification tests in addition to routine testing, but this remains unfeasible in many settings.

Summary: Finding HIV testing strategies that are affordable and practical in low- and middle-income countries that can accurately diagnose HIV in the context of HIV prevention is of high importance, but more research is needed in this area.

Purpose of review: This review summarizes recent research literature relevant to mucosal immunity and acute/early HIV infection.

Recent findings: Recent findings include new insights on the HIV transmission "bottleneck" at mucosal surfaces, the impact of acute HIV on germinal centers and mucosal B-cell function, the expression of cytotoxic effector molecules by mucosal CD8 + T-cells, and an enhanced understanding of the impact of acute HIV on innate cell-mediated defenses including mucosa-associated invariant T-cells invarant natural killer T-cells and natural killer cells.

Summary: Now more than 40 years since the beginning of the HIV/AIDS pandemic, extensive research has elucidated the dynamics of HIV replication and the corresponding host response. However, the vast majority of HIV-related immunopathogenesis studies have focused on innate and adaptive immune responses in peripheral blood. Mucosal tissues serve as the primary portals of entry for HIV and house the majority of the body's lymphocytes. Innate and adaptive immune responses in mucosal tissues are of particular relevance during the acute phase of HIV disease, as successful defenses can both limit viral dissemination within the host and prevent transmission to a new host, yet until recently these responses were poorly understood.

Purpose of review: The earliest months of HIV infection are characterized by high viral loads and elevated transmissibility, particularly during the acute (preseroconversion) phase. Transmission prevention during early HIV requires diagnostic tools that narrow the window between viral acquisition and reactive test, followed by rapid linkage to effective antiretroviral therapy (ART). Here, we review recent advances related to diagnosing and treating persons during early HIV, with a particular focus on acute HIV infection (AHI).

Recent findings: Point-of-care (POC) fourth-generation antigen/antibody tests have mixed performance, often dependent on the pretest probability of early infection within the screened population. Risk score algorithms demonstrate the potential for prioritizing resource-intensive tests, such as POC HIV RNA, to those most likely to have AHI, but their predictive performance varies across populations, complicating implementation. Emerging and re-emerging infections, including SARS-CoV-2 and mpox, present opportunities for and challenges to symptom-driven AHI screening. Daily oral ART with standard first-line regimens quickly suppresses viremia during AHI, but long-acting injectable drugs are yet to be explored for this indication.

Summary: Few practice-changing results related to diagnosing or treating persons with early HIV have been released in the last 18 months. Accurate POC HIV RNA tests could leapfrog fourth-generation POC assays, but they remain unavailable for routine use. Implementation science approaches are needed to guide use of evidence-based strategies for early HIV screening, and additional research on same-day ART linkage, including injectable ART, could produce dramatic impacts on forward transmission during this period.

Purpose of review: To review the concept of autovaccination as a strategy to boost anti-HIV-1 immunity and improve immune control, especially as a means to facilitate cure/remission in paediatric HIV-1 infection, where effective interventions in clinical testing remain limited compared to adults.

Recent findings: Early autovaccination studies, conducted 15-25 years ago, suggested potential immunological benefits from exposure to autologous virus in both children and adults, specifically when antiretroviral therapy (ART) was initiated during acute infection. More recent work in nonhuman primates (NHPs) has shown that early ART initiation can significantly reduce the viral setpoint following treatment interruption, primarily through CD8 + T-cell responses, and prevent early immune escape - a phenomenon commonly observed in ART-naive acute infections. Additionally, NHP studies indicate that multiple, short analytical treatment interruptions (ATIs) can delay viral rebound and further lower the viral setpoint via enhanced CD8 + T-cell responses.

Summary: Recent studies in NHP support the potential for autovaccination via short ATIs to enhance antiviral immunity and improve immune control of HIV-1. With well tolerated, well monitored ATI protocols, autovaccination could be a valuable approach to facilitating cure/remission in children living with HIV (LWH), in whom very early-ART initiation and early-life immunity are associated with low viral reservoirs and high cure/remission potential.

Purpose of review: Sexually transmitted infections (STIs) are a significant global health concern, with many cases going undiagnosed due to asymptomatic infections. Traditional diagnostic methods, such as culture and serology, have limitations in sensitivity, specificity, and turnaround time. Molecular diagnostics, particularly PCR-based approaches, offer significant advantages, including improved detection rates and the potential for syndromic testing. This review examines the role of syndromic PCR diagnostics in improving STI detection and management.

Recent findings: Recent studies highlight the utility in detecting common STIs, such as Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis , as well as emerging pathogens. PCR-based syndromic panels allow for the simultaneous detection of multiple pathogens from a single sample, improving diagnostic accuracy and efficiency. Syndromic PCR approaches streamline diagnosis, aid in early detection, and support efficient treatment, addressing both common and emerging infections.

Summary: Syndromic PCR diagnostics streamline STI detection, addressing the limitations of conventional methods. They enable faster, more accurate, and comprehensive diagnosis, leading to targeted treatment and improved patient outcomes. Expanding syndromic panels to include emerging pathogens and ensuring cost-effective implementation remain key areas for future research.

Purpose of review: The evolving landscape of HIV treatment for children now extends beyond viremic control with daily antiretroviral treatment (ART), with new approaches that sustain viral suppression while permitting breaks from small molecule ART now reaching the clinical trial stage. Trials involving broadly neutralizing monoclonal antibodies (bNAbs) have commenced in selected pediatric populations. Evidence from adult bNAb studies suggests that bNAbs might reduce latent viral reservoirs, fostering hope that these agents could offer a pathway to posttreatment control, which is seldom achievable with small molecule ART.

Recent findings: Few pediatric studies to date have used bNAbs in the setting of existing HIV infection to improve treatment outcomes. Safety and pharmacokinetic (PK) data from IMPAACT 2012, IMPAACT 2008, and the Tatelo Study have been reassuring. The Tatelo Study in Botswana first used combination bNAbs (VRC01LS, 10-1074) as an alternative treatment strategy in children aged 2-5 years who started ART near birth, showing that nearly half of unscreened children could maintain viral suppression with dual bNAbs alone, and identifying predictors for success. From a viral reservoir standpoint, IMPAACT 2008 identified a possible dose-dependent effect of VRC01, with higher plasma VRC01 concentrations being associated with lower HIV-1 DNA. Further reservoir data are expected from Tatelo Plus (IMPAACT 2042), which began enrolling in 2024 and will evaluate a triple bNAb combination (VRC07-504LS, PGDM1400LS, and PGT.121.LS) with the addition of an analytic treatment interruption (ATI) in some children. IMPAACT P1115, which recently reported successful ATI in selected low-reservoir children, is evaluating the addition of VRC01 or VRC-07-523LS on viral reservoir and treatment outcomes. Looking to the future, IMPAACT 2039 will evaluate VRC07-523LS + PGT121.414LS as part of a combination intervention, and the SNOW study will evaluate VRC07-523LS during a series of ATIs.

Summary: This review synthesizes data for ongoing and planned pediatric bNAb treatment studies, focusing on available trial results that underscore the ability of newer and more potent long-acting bNAbs to sustain viral suppression. We discuss the potential impact of bNAbs to reduce the latent viral reservoir and their use as a strategy to achieve viral remission in children with HIV.

Purpose of review: Although cases of Zika virus disease (ZVD) have declined globally since 2017, new outbreaks have been reported, such as in Asia in 2024. As there is no vaccine or treatment available to date, both vaccines and mAbs neutralizing Zika virus would be of great interest, especially for pregnant women and immunocompromised patients such as those living with HIV. This review focuses on new insights regarding ZVD in the last two years and summarizes the key literature on global epidemiology, transmission, diagnostics, clinical features, preventive measures, and treatment options.

Recent findings: At the time of writing, ZVD is endemic across tropical and subtropical regions of the world, with the highest risk of infection in Latin America and the Caribbean, but no significant peaks in outbreak activity across endemic regions. There are ongoing efforts to further investigate the clinical and epidemiological long-term sequelae of the large outbreak in the Americas 2015-2018; further refinement of diagnostic tools to improve specificity in view of significant cross-reactivity potential, particularly with dengue virus. Multiple vaccines are in different clinical development stages; however, phase 3 trials are awaiting the next epidemic.

Summary: While there is no current major zika virus outbreak, progress has been made in the epidemiological work-up of clinical-epidemiological data, refinement of diagnostic tools, and mainly preventive (vaccines) rather than curative (drugs) tools.

Purpose of review: The SARS-CoV-2 pandemic presented unprecedented challenges, particularly in understanding its complex spatial transmission patterns. The high transmissibility of the virus led to frequent super-spreading events. These events demonstrated clear spatial clustering patterns, often tied to specific events that facilitated transmission. The uneven geographic distribution of medical resources and varying access to care amplified the impact of SARS-CoV-2. Asymptomatic cases further complicated the situation, as infected individuals could silently spread the virus before being identified.Thus, this review examines how genomic and spatial epidemiology approaches can be integrated to answer some of the above-mentioned challenges. We first describe the methodological foundations of genomics and spatial epidemiology, detailing opportunities of their applications during the SARS-CoV-2 pandemic. We then present a novel interdisciplinary framework that combines these approaches to better guide public health interventions.

Recent findings: During the pandemic, the genomic and spatial approaches were used to address key questions, including "how does the pathogen evolve and diversify?" and "how does the pathogen spread geographically?". Genomic epidemiology allows researchers to identify viral lineages and new variants. Conversely, spatial epidemiology focused on geographic distribution of infections, analyzing how the virus spread. However, despite their complementary nature, these approaches were largely applied independently during the pandemic. This separation limited our collective ability to fully understand the complex relationships between viral evolution and geographic spread.

Summary: While phylogeography has traditionally combined phylogenetic and geographic data to understand long-term evolutionary patterns across large areas, events such as the recent SARS-CoV-2 pandemic demand frameworks that can inform public health interventions through joint analysis of genomic and local-scale spatial data.

Purpose of review: The neuropathogenesis of acute HIV leads to rapid central nervous system (CNS) involvement, characterized by early viral entry, immune activation, and the formation of viral reservoirs. Despite effective antiretroviral therapy (ART), these reservoirs persist, drive neuroinflammation and injury and lead to HIV-associated neurodegenerative disorders (HAND). This review provides an updated synthesis of the mechanisms in acute HIV neuropathogenesis, biomarkers of CNS injury and emerging therapeutic approaches. A deeper understanding of these mechanisms is critical for addressing persistent HAND in ART-treated individuals.

Recent findings: Growing evidence now supports the principal role of infected CD4 + T cells in mediating HIV neuroinvasion alongside monocytes, resulting in seeding in perivascular macrophages, pericytes, and adjacent microglia and astrocytes. These reservoirs contribute to ongoing transcriptional activity and viral persistence despite antiretroviral therapy. Neuroinflammation, driven by activated microglia, astrocytes, inflammasomes, and neurotoxic viral proteins, disrupts neuronal homeostasis. Emerging therapies, including latency-reversing agents and transcription inhibitors, show promise in reducing neuroinflammation and reservoir activity.

Summary: Understanding the mechanisms of HIV neuropathogenesis and reservoir persistence has significant implications for developing targeted therapies to mitigate HAND. Strategies to eliminate CNS reservoirs and reduce neuroinflammation should be prioritized to improve long-term cognitive outcomes in people with HIV.