Current opinion in HIV and AIDS最新文献

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: Clinical and virological outcomes in early-treated cohorts of children living with HIV have been sub-optimal. This is in part due to the demands on the caregiver of adhering to twice a day antiretroviral treatment (ART) for their newborn infants. Administering ART to neonates can be challenging and frequently requires separate drugs in liquid formulations and multiple dose adjustments. We reviewed literature from 01 January 2015 to 31 December 2024 on infant outcomes, antiretroviral drugs, updated dosing recommendations, new formulations and potential strategies to enhance adherence when ART is started in the neonatal and young infant period.

Recent findings: There are now pharmacokinetic (PK) data to inform the use of abacavir and lamivudine in liquid and solid formulations in the neonatal period and to support the use of lamivudine and nevirapine in preterm infants. A dosing strategy for dolutegravir in the first month of life has been informed by recent studies.

Summary: Studies are ongoing with regards to dolutegravir in various formulations. Long-acting antiretroviral therapy and broadly neutralizing antibodies are currently being studied in neonates and young infants. Addressing maternal clinical and psychosocial health and is a key factor in ensuring infants achieve viral suppression and decreased morbidity.

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: Despite decades of insights about the role of natural killer (NK) cells in HIV infection, their persistent dysregulation despite antiretroviral therapy (ART) and its pathological consequences have been incompletely delineated. In this review, we highlight recent findings on the immunophenotypic and functional alterations of NK cells during virally suppressed HIV infection and explore their potential impact on promoting non-AIDS related comorbidities among people living with HIV (PLWH).

Recent findings: Of note are the apparent persistent activated profiles of NK cells and pathophysiological events such as endoplasmic reticulum (ER) stress in potentially driving NK cell derived inflammation and tissue destruction. Additionally, recent interest in trained immunity is discussed as a potential mediator of ongoing NK cell dysregulation, contributing to comorbidities such as cardiovascular disease and neurocognitive disorders, both with an inflammatory etiology.

Summary: Clinical and mechanistic evidence suggests persistent activation and dysregulation of the innate immune system are major drivers of non-AIDS comorbidities during virally suppressed HIV infection. Delineating the mechanistic role of specific components of innate immunity such as NK cells in inducing these pathologies will lead to the identification of novel therapeutic/prophylactic strategies to improve the overall health of PLWH.

Purpose of review: Like elephants (and T cells), accumulating evidence suggest natural killer (NK) cells never forget. The description of adaptive or memory NK cells, which can be induced by HIV/SIV infections and vaccines and associated with protective effects in persons with HIV (PWH), has dramatically increased the interest in leveraging NK cells to prevent HIV infection or suppress HIV reservoirs. However, harnessing their full antiviral potential has been hindered by an incomplete understanding of mechanisms underlying adaptive NK cell development and infected cell recognition. Herein, we outline the main discoveries around the adaptive functions of NK cells, with a focus on their involvement in HIV infection.

Recent findings: NK cells with diverse adaptive capabilities, including antigen-specific memory, cytokine-induced and CMV-driven adaptive subsets, likely all play a role in HIV infection. Importantly, true antigen-specific memory NK cells have been identified that mediate recall responses against multiple infectious agents such as HIV, influenza, and SARS-CoV-2. The NKG2C receptor is pivotal for certain adaptive NK cell subsets, as it marks a population with enhanced antibody-dependent functions and has been described as the main receptor mediating antigen-specific responses via recognition of viral peptides presented by HLA-E.

Summary: Antiviral functions of adaptive/memory NK cells have tremendous, but as of yet, untapped potential to be harnessed for vaccine design, curative, or other therapeutic interventions against HIV.

Purpose of review: Antiretroviral therapy (ART) has significantly extended the life expectancy of people with HIV (PWH). However, as this population ages, they face increased risk of social isolation and loneliness (SIL), driven by stigma, discrimination, and shrinking social networks. SIL is a major public health issue, closely linked to mental health conditions, reduced adherence to treatment, and lower health-related quality of life (HRQoL). This review examines the prevalence, risk factors, health impacts, and interventions related to SIL, highlighting its critical importance for improving HRQoL in PWH.

Recent findings: SIL is common among PWH and strongly associated with HIV-related stigma, depression, anxiety, and systemic inflammation. These factors accelerate aging and contribute to chronic conditions while undermining ART outcomes. Recent research supports the effectiveness of interventions like psychological therapies and social prescribing in reducing SIL and improving HRQoL. However, progress is limited by the lack of standardized tools to assessment SIL, which hampers consistent research and the development of targeted solutions.

Summary: Addressing SIL is essential to advancing holistic and person-centered HIV care. Integrating SIL evaluation into routine clinical practice, creating standardized assessment tools, and implementing targeted interventions can improve HRQoL and reduce health burdens, particularly as the aging PWH population grows.

Purpose of review: This review highlights the role of monocytes in the pathogenesis of HIV-1 infection, focusing on their involvement in the inflammatory response and their function as viral targets and long-term reservoirs.

Recent findings: Monocytes have been categorized into three subsets: classical, intermediate, and nonclassical, each with distinct functional characteristics. Advances in genetic sequencing technologies have enabled a more in-depth exploration of the phenotypic and functional variations among these subsets, particularly in the context of HIV. These findings underscore their role as crucial components of the immune response and as reservoirs for the virus.

Summary: Previous studies on the role of monocytes have demonstrated their contribution to persistent infection and chronic immune activation, especially in adults living with HIV. The lessons learned from these studies should now be harnessed to design studies focused on newborns and children with vertically acquired HIV.

Purpose of review: Natural killer (NK) cells are integral components of the innate immune system, serving a vital function in eliminating virally infected cells. This review highlights the significance of CXCR5+ NK cells in the context of chronic HIV/SIV infection and viral control.

Recent findings: Controlled HIV/SHIV infection results in a substantial increase in the population of CXCR5+ NK cells within the B-cell follicles of secondary lymphoid organs (SLOs). These CXCR5+ NK cells display enhanced functional characteristics, including elevated expression of activation markers and increased cytokine production, which are essential for effective viral control. These follicular NK cells are shown to be enriched in IL-15 signaling, and CXCR5 NK cells are negatively associated with viral burden during chronic HIV and SHIV infection.

Summary: The distinct phenotypic and functional attributes of CXCR5+ NK cells, particularly in the lymphoid tissues of individuals living with HIV, emphasize their critical contribution to the anti-HIV-1 immune response. A comprehensive understanding of the mechanisms and roles of CXCR5+ NK cells may present novel therapeutic strategies aimed at enhancing NK-mediated viral control.

Purpose of review: Typically, both HIV-infected humans and simian immunodeficiency virus (SIV)-infected Asian nonhuman primates (NHPs) eventually progress to AIDS, while African NHPs that are natural hosts of SIV do not, in spite of life-long, high levels of viral replication. Lack of disease progression in African NHPs is not due to some adaptation by the virus, but rather to host adaptations to the virus. Central to these adaptations is maintenance of the gut integrity during acute viral replication and inflammation, which allows natural hosts to avoid the chronic inflammation characteristic to pathogenic HIV/SIV infection.

Recent findings: It has been recently shown that natural hosts of SIVs, such as the African green monkey (AGM), avoid damage to the mucosal epithelium through wound healing mechanisms, possibly with the contribution of a unique anti-inflammatory microbiome. Furthermore, these mechanisms are independent of viral replication, and CD4 + T-cell activation or depletion.

Summary: Future SIV research on natural hosts should focus on further elucidating the anti-inflammatory state of their gut, and the role of microbiome/dysbiosis in the pathogenesis of SIV infection, with the goal of development new regiments or treatments to reduce or even halt the vicious cycle of gut damage and inflammation triggered by pathogenic HIV/SIV infection.